高原世居藏族与移居汉族胎盘线粒体能量代谢的比较研究
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摘要
世居高原的藏族人群居住高原年代最长且较为封闭,他们具有更完善的氧运输和氧利用的能力,胎儿在宫内发育迟缓少、婴儿出生体重较重、新生儿氧合效率高,是目前公认对于高原低氧环境适应(adaptation)最好的民族[1-2]。
有关世居藏族高原低氧适应的机制目前还不清楚。以往的研究显示,高原世居藏族与移居汉族相比,做同等量的功时藏族的耗氧量显著低于汉族,提示藏族在组织、细胞水平对氧的利用率更高,可能是其高原适应的重要机制[3]。我们的研究还发现,线粒体结构和功能的改变是动物习服(acclimatization)低氧环境的重要机制[4]。青藏高原世居藏族在高原低氧环境下已经生活了至少25 000年[3],且由于历史上青藏高原地理环境的封闭性和藏族婚俗的对外隔离性,其遗传学特性得以很好地保存下来。我们推测,世居高原藏族线粒体对于低氧环境的适应性改变可能通过自然选择的作用固定下来,并由此获得了较其他高原世居人群和移居人群更好的对高原低氧环境的适应能力。不过,对于线粒体的研究多在实验动物上进行,关于高原世居者线粒体在低氧适应机制中的作用迄今国内、外均未见文献报道。为此,我们首次在西藏高原地区研究和比较了高原世居藏族和移居汉族胎盘线粒体能量代谢功能,为探索世居高原藏族低氧适应的本质提供新的线索和思路。
方法
纳入标准月经周期规律、末次月经明确、无烟酒嗜好、孕期37~42周,无高血压、糖尿病、心肺疾病、遗传病及传染病的世居藏族和移居汉族产妇。自愿者分为高原世居藏族组(T组)和高原移居汉族组(H组),两组产妇年龄、体重指数相匹配。比较二组产妇胎盘体积,胎盘重量,胎盘系数,比较二组新生儿低体重出生率,新生儿出生体重和身长。
分离提取胎盘线粒体,利用透射电子显微镜观察二组胎盘组织线粒体的超微结构,以Clark氧电极法测定线粒体氧化呼吸活性、复合体I,II,IV活性,以定磷法测定F0-F1 ATP酶活性,高效液相法(HPLC)分析胎盘组织及胎盘线粒体内腺苷酸含量,罗丹明123荧光流动透析法测线粒体膜电位,反转录PCR检测ANTmRNA表达量,Western blot测定ANT蛋白表达,3H-ADP摄入法测定ANT的转运速率。
结果
1.世居藏族胎盘体积,重量和胎盘系数显著高于移居汉族,世居藏族新生儿出生体重和身长显著高于移居汉族,世居藏族新生儿低体重出生率显著低于移居汉族。
2.胎盘线粒体电镜观察:高原藏族线粒体大部分完整,偶尔有线粒体肿胀,空泡移居汉族线粒体广泛肿胀,空泡化,嵴脱落有些可见少量细胞核成分,大多细胞胞浆疏松。
3.世居藏族胎盘光镜下表现:绒毛直径较小,表面积增加;绒毛间含丰富的毛细血管,呈血窦样扩张;合体结节形成。移居汉族胎盘光镜下表现:绒毛间质水肿;绒毛间质血管减少;绒毛纤维素增多。
4.世居藏族胎盘线粒体复合体I,II及F0F1- ATP酶活性显著高于移居汉族。
5.世居藏族胎盘线粒体三态呼吸ST3,呼吸控制率RCR,氧化磷酸化效率OPR显著高于移居汉族。
6.世居藏族胎盘线粒体膜电位,胎盘线粒体ATP含量,胎盘组织腺苷酸池ATP/ADP和能荷都高于移居汉族。
7.移居汉族ANTmRNA表达显著高于世居藏族。二组ANT的蛋白表达没有差异,世居藏族ANT转运活性显著高于移居汉族。
结论
1.高原环境影响移居汉族胎儿宫内的生长发育。因此,有必要进一步探索高原环境对移居汉族胎儿生长发育的影响机制,以利于加强移居者围产期保健,降低高原缺氧环境对移居者胎儿生长发育的不良影响。
2.在高原缺氧环境中,与世居藏族相比,移居汉族胎盘线粒体呼吸链复合体I,II的酶活性和3态呼吸氧耗速率显著降低,膜电位降低,从而导致氧化磷酸化效率降低,线粒体ATP的合成减少。
3.与世居藏族相比,移居汉族胎盘在缺氧环境中,基础氧耗没有增加,ANT核反应增强,这可能是移居汉族高原习服的机制。
4.世居藏族胎盘线粒体能量的生成高于移居汉族,这可能是世居藏族对慢性低氧适应的重要机制。
The Zang nationality live longest and closed in high altitude.They have more consummate ability of transporting and using oxygen.There are a few intrauterine growth retardation(IUGR).The higer birth weight and the efficient oxygenation make them generally accepted as the best nation of adaptation to high altitude.
It is not clear about the mechanism of Zang nationality adaptation to high altitude.It was evidenced that the consumed oxygen by Zang were lower than by Han when they do the coordination duty.This state the better availability in cellular level of Zang may be the important mechanism of adaptation to high altitude.The mitochondrial changes of structure and function is the important mechanism of animal acclimatization to hypoxia environment.The Zang nationality live in high altitude more than about 25 000years,the genetic characteristic of them can be conserved well because of the closed environment and the isolated marriage.We presume the adaptation to hypoxia of Zang nationality maybe fixed through the natural selection.Hence they have the better ability to adaptation hypoxia environment than other nations.The most reseach about mitochondria were done in animal model before.There is no report about the mechanism of mitochondrial adaptation in hypoxia in permanent high altitude native . To expore the mechanism of Zang nationality adaptation to hypoxia,we reseach and compare the placental mitochondrial energy metabolism between nationality Zang and immigrant Han in high altitude.
Methods
The healthy Zang nationality(Z group) and the immigrant Han(H group) pregnant woman were recruited.Their gestation were 37~42 weeks.There is no different of ages and body mass index between them.Comprasion the placental size, the placental weight, the placental ratio, the birth weight, the fetus body lenth, and the low birth rate between the two group.
Isolation and abstraction the placental mitochondria, measurement the ST3, ST4, respiratory control rate(RCR), the complexI, II, IV of mitochondrial breath train by Clark oxygen electrode.F0-F1 ATP enzyme activity by measure P, the content of adenine nucleotide in placenta and mitochondria by HPLC; the ANT transport activity by H3-ADP intake; the mitochondrial membrane potential by Rhodamine 123 fluorescence; ANT mRNA expression by reverse PCR; ANT protein expression by Western blot. Observation the placental mitochondrial ultramicrostructure and morphology of the two groups by electro- microscope and light microscope..
Results
1. The placenta size, weight and placental ratio of Zang nationality are higher than immigrant Han; The birth weiht, the fetus body lenth of Zang nationality are higher than immigrant Han; The low birth weight of Zang nationality are lower than immigrant Han.
2. The result of placental mitochondrial electrodemicroscope were: Most of placental mitochondria structure of Zang nationality are integraty, while most of placental mitochondria structure of immigrant Han are swelling, vacuolus, cristae shedding, most kytoplasm raritas.
3. The result of placental mitochondrial morphology of Zang nationality were: the smaller diameter of villus, the bigger surface area of villus, the affluent capillary between the villus, zoarium tuberculation. The result of placental mitochondrial morphology of immigrant Han were: the villus interstitial edema, the less capillary of villus interstitial, the increased villus fiber.
3. The activity of placental breath train complex I, II, and F0-F1 ATPase enzymatic of Zang nationality are higher than that of immigrant Han.
4. The ST3, RCR, OPR of are higher than that of immigrant Han.
5. The placental mitochondrial membrane potential, the content of ATP in placenta and mitochondria of Zang nationality are higher than those of immigrant Han; the placenta adenylate pool ATP/ADP and energy charge of Zang nationality are higher than those of immigrant Han.
6. The ANT mRNA expression of Zang nationality are lower significantly than that of immigrant Han; the ANT protein expression is no difference between the two groups; ANT transport activity of Zang nationality are higher than that of immigrant Han.
Conclusion
1. The fetus development of immigrant Han are effected by high altitude environment.In order to enhance the perinatal care of the immigrant and reduce the harmful effecion of the hypoxia in high altitude, so it’s nessasery to explore the mechanism of this effection.
2.Compared with the Zang nationality, under the hypoxia environment, the placenta mitochondrial ST3, RCR, membrane potential of immigrant Han was decreased, lead to reduce the ATP synthesis.
3.Compared with Zang nationality, the basic oxygen consumption didn’t increase and the expression of ANT mRNA increased in the immigrant Han , which maybe be the acclimatization mechanism to high altitude of immigrant Han.
4.It’s maybe the important mechanism of adaption to hypoxia in high altitude of Zang nationality that the placental mitochondrial energy metabolismo of them are higer than that of immigrant Han.
有关世居藏族高原低氧适应的机制目前还不清楚。以往的研究显示,高原世居藏族与移居汉族相比,做同等量的功时藏族的耗氧量显著低于汉族,提示藏族在组织、细胞水平对氧的利用率更高,可能是其高原适应的重要机制[3]。我们的研究还发现,线粒体结构和功能的改变是动物习服(acclimatization)低氧环境的重要机制[4]。青藏高原世居藏族在高原低氧环境下已经生活了至少25 000年[3],且由于历史上青藏高原地理环境的封闭性和藏族婚俗的对外隔离性,其遗传学特性得以很好地保存下来。我们推测,世居高原藏族线粒体对于低氧环境的适应性改变可能通过自然选择的作用固定下来,并由此获得了较其他高原世居人群和移居人群更好的对高原低氧环境的适应能力。不过,对于线粒体的研究多在实验动物上进行,关于高原世居者线粒体在低氧适应机制中的作用迄今国内、外均未见文献报道。为此,我们首次在西藏高原地区研究和比较了高原世居藏族和移居汉族胎盘线粒体能量代谢功能,为探索世居高原藏族低氧适应的本质提供新的线索和思路。
方法
纳入标准月经周期规律、末次月经明确、无烟酒嗜好、孕期37~42周,无高血压、糖尿病、心肺疾病、遗传病及传染病的世居藏族和移居汉族产妇。自愿者分为高原世居藏族组(T组)和高原移居汉族组(H组),两组产妇年龄、体重指数相匹配。比较二组产妇胎盘体积,胎盘重量,胎盘系数,比较二组新生儿低体重出生率,新生儿出生体重和身长。
分离提取胎盘线粒体,利用透射电子显微镜观察二组胎盘组织线粒体的超微结构,以Clark氧电极法测定线粒体氧化呼吸活性、复合体I,II,IV活性,以定磷法测定F0-F1 ATP酶活性,高效液相法(HPLC)分析胎盘组织及胎盘线粒体内腺苷酸含量,罗丹明123荧光流动透析法测线粒体膜电位,反转录PCR检测ANTmRNA表达量,Western blot测定ANT蛋白表达,3H-ADP摄入法测定ANT的转运速率。
结果
1.世居藏族胎盘体积,重量和胎盘系数显著高于移居汉族,世居藏族新生儿出生体重和身长显著高于移居汉族,世居藏族新生儿低体重出生率显著低于移居汉族。
2.胎盘线粒体电镜观察:高原藏族线粒体大部分完整,偶尔有线粒体肿胀,空泡移居汉族线粒体广泛肿胀,空泡化,嵴脱落有些可见少量细胞核成分,大多细胞胞浆疏松。
3.世居藏族胎盘光镜下表现:绒毛直径较小,表面积增加;绒毛间含丰富的毛细血管,呈血窦样扩张;合体结节形成。移居汉族胎盘光镜下表现:绒毛间质水肿;绒毛间质血管减少;绒毛纤维素增多。
4.世居藏族胎盘线粒体复合体I,II及F0F1- ATP酶活性显著高于移居汉族。
5.世居藏族胎盘线粒体三态呼吸ST3,呼吸控制率RCR,氧化磷酸化效率OPR显著高于移居汉族。
6.世居藏族胎盘线粒体膜电位,胎盘线粒体ATP含量,胎盘组织腺苷酸池ATP/ADP和能荷都高于移居汉族。
7.移居汉族ANTmRNA表达显著高于世居藏族。二组ANT的蛋白表达没有差异,世居藏族ANT转运活性显著高于移居汉族。
结论
1.高原环境影响移居汉族胎儿宫内的生长发育。因此,有必要进一步探索高原环境对移居汉族胎儿生长发育的影响机制,以利于加强移居者围产期保健,降低高原缺氧环境对移居者胎儿生长发育的不良影响。
2.在高原缺氧环境中,与世居藏族相比,移居汉族胎盘线粒体呼吸链复合体I,II的酶活性和3态呼吸氧耗速率显著降低,膜电位降低,从而导致氧化磷酸化效率降低,线粒体ATP的合成减少。
3.与世居藏族相比,移居汉族胎盘在缺氧环境中,基础氧耗没有增加,ANT核反应增强,这可能是移居汉族高原习服的机制。
4.世居藏族胎盘线粒体能量的生成高于移居汉族,这可能是世居藏族对慢性低氧适应的重要机制。
The Zang nationality live longest and closed in high altitude.They have more consummate ability of transporting and using oxygen.There are a few intrauterine growth retardation(IUGR).The higer birth weight and the efficient oxygenation make them generally accepted as the best nation of adaptation to high altitude.
It is not clear about the mechanism of Zang nationality adaptation to high altitude.It was evidenced that the consumed oxygen by Zang were lower than by Han when they do the coordination duty.This state the better availability in cellular level of Zang may be the important mechanism of adaptation to high altitude.The mitochondrial changes of structure and function is the important mechanism of animal acclimatization to hypoxia environment.The Zang nationality live in high altitude more than about 25 000years,the genetic characteristic of them can be conserved well because of the closed environment and the isolated marriage.We presume the adaptation to hypoxia of Zang nationality maybe fixed through the natural selection.Hence they have the better ability to adaptation hypoxia environment than other nations.The most reseach about mitochondria were done in animal model before.There is no report about the mechanism of mitochondrial adaptation in hypoxia in permanent high altitude native . To expore the mechanism of Zang nationality adaptation to hypoxia,we reseach and compare the placental mitochondrial energy metabolism between nationality Zang and immigrant Han in high altitude.
Methods
The healthy Zang nationality(Z group) and the immigrant Han(H group) pregnant woman were recruited.Their gestation were 37~42 weeks.There is no different of ages and body mass index between them.Comprasion the placental size, the placental weight, the placental ratio, the birth weight, the fetus body lenth, and the low birth rate between the two group.
Isolation and abstraction the placental mitochondria, measurement the ST3, ST4, respiratory control rate(RCR), the complexI, II, IV of mitochondrial breath train by Clark oxygen electrode.F0-F1 ATP enzyme activity by measure P, the content of adenine nucleotide in placenta and mitochondria by HPLC; the ANT transport activity by H3-ADP intake; the mitochondrial membrane potential by Rhodamine 123 fluorescence; ANT mRNA expression by reverse PCR; ANT protein expression by Western blot. Observation the placental mitochondrial ultramicrostructure and morphology of the two groups by electro- microscope and light microscope..
Results
1. The placenta size, weight and placental ratio of Zang nationality are higher than immigrant Han; The birth weiht, the fetus body lenth of Zang nationality are higher than immigrant Han; The low birth weight of Zang nationality are lower than immigrant Han.
2. The result of placental mitochondrial electrodemicroscope were: Most of placental mitochondria structure of Zang nationality are integraty, while most of placental mitochondria structure of immigrant Han are swelling, vacuolus, cristae shedding, most kytoplasm raritas.
3. The result of placental mitochondrial morphology of Zang nationality were: the smaller diameter of villus, the bigger surface area of villus, the affluent capillary between the villus, zoarium tuberculation. The result of placental mitochondrial morphology of immigrant Han were: the villus interstitial edema, the less capillary of villus interstitial, the increased villus fiber.
3. The activity of placental breath train complex I, II, and F0-F1 ATPase enzymatic of Zang nationality are higher than that of immigrant Han.
4. The ST3, RCR, OPR of are higher than that of immigrant Han.
5. The placental mitochondrial membrane potential, the content of ATP in placenta and mitochondria of Zang nationality are higher than those of immigrant Han; the placenta adenylate pool ATP/ADP and energy charge of Zang nationality are higher than those of immigrant Han.
6. The ANT mRNA expression of Zang nationality are lower significantly than that of immigrant Han; the ANT protein expression is no difference between the two groups; ANT transport activity of Zang nationality are higher than that of immigrant Han.
Conclusion
1. The fetus development of immigrant Han are effected by high altitude environment.In order to enhance the perinatal care of the immigrant and reduce the harmful effecion of the hypoxia in high altitude, so it’s nessasery to explore the mechanism of this effection.
2.Compared with the Zang nationality, under the hypoxia environment, the placenta mitochondrial ST3, RCR, membrane potential of immigrant Han was decreased, lead to reduce the ATP synthesis.
3.Compared with Zang nationality, the basic oxygen consumption didn’t increase and the expression of ANT mRNA increased in the immigrant Han , which maybe be the acclimatization mechanism to high altitude of immigrant Han.
4.It’s maybe the important mechanism of adaption to hypoxia in high altitude of Zang nationality that the placental mitochondrial energy metabolismo of them are higer than that of immigrant Han.
引文
1. Moore LG, Armaza F, Villena M, et a1. Comparative aspects of high-altitude adaptation in human populations. Adv Exp Med Biol, 2000,475:45-62.
2. 吴天一. 藏族——高原适应的佼佼者. 大自然, 2005,3:4-6.
3. More LG, Zamudio S, Jorde LB, el a1. 高原遗传性适应. 西藏医药杂志, 1997, 8: 6-15.
4. 高文祥, 柳君泽, 吴利平, 等. 急、慢性缺氧对大鼠脑线粒体能量代谢的影响. 中国病理生理学杂志, 2000,16:879-882.
5. Zharova TV, Vinogradov AD. Energy-linked binding of Pi is required for continuous steady-state proton-translocating ATP hydrolysis catalyzed by F0.F1-ATP synthase. Biochemistry, 2006, 45(48):14552-14558.
6. Nury H, Dahout-Gonzalez C, Trezequet V, et al. Relations between structure and function of the mitochondrial ADP/ATP carrier. Annu Rev Biochem, 2006, 75:713-741.
7. Vyssokikh MY, Katz A, Rueck A,et al. Biochem-J. Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophilin D.2001, 358: 349-358.
8. Dolce A, Scarcia P, Iacopetta D, et al. A fourth ADP/ATP carrier isoform in man: identification, bacterial, expression, functional characterization and tissue distribution. FEBS Letters, 2005, 579: 633-637.
9. Voos W, Martin H, Krimmer T, et al. Mechanisms of protein translocation into mitochondria. Biochim Biophys Acta, 1999, 1422(3): 235-254.
10. Peter Gluckman , Mark Hanson.The Fetal Matrix Evolution,Development and Disease[M]. Cambridge University Press, 2005, 257.
11. Lawlor DA,Ronalds G. Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s:findings from the Aberdeen Children of the 1950s prospective cohort study [J]. Circulation, 2005, 6(10): 1414-1418.
12. Lawlor DA, Ebrahim S.Association of birth weight with adult lung function:findings from the British Women’s Heart and Health Study and a meta-analysis [J]. Thorax, 2005, 60(10): 851-858.
13. Wu TY, Tu DT, Zhau GL, etal. The physiological differences between the Tietans and the Andeans.In:OhnoH,KobayashiT,Masuyama Sand NakashimaM(eds), Progress of Mountain Medicine and HighAltitude Physology [J] . SMM, Tokorozawa, Matsumoto, 1998, 190~194.
14. Adair FL, Thelander H. A study of the weight and dimensions of the human placenta in its relation to the weight of the newborn infant [J] . Am J Obstet Gynecol, 1925, 10: 172– 205.
15. Adair FL, Thelander H. A study of the weight and dimensions of the human placenta in its relation to the weight of the newborn infant[J]. Am J Obstet Gynecol,1925,10:172– 205.
16. 王军,王志农,李素芝,等.拉萨市6500名小学生先天性心脏病调查[J].西藏科技,2002,(1):12-14
17. ZamudioS. The placenta at high altitude[J]. High Alt Med Biol,2003,4(2):171-191.
18. Moore LG, Shriver M, Bemis L, et al. Maternal adaptation to high-altitude pregnancy :an experiment of nature —a review [J]. Placenta, 2004, 25(suppl A):60– 71.
19. Fionnuala Mc Auliffe, Nikos Kametas, Elisabeth Krampl. Blood gases in pregnancy at sea level and at high altitude [J].British Journal of Obstetrics and Gynaecology, 2001, 108(9): 980-985.
20. Mortola JP, Frapell PB, Agqero L, et al. Birth weight and altitude: a study in Peruvian communities [J]. Peadiatr, 2000, 136(33):324–329.
1. More LG, Zamudio S, Jorde LB, el a1. 高原遗传性适应. 西藏医药杂志, 1997, 8: 6-15.
2. 吴天一.藏族——高原适应的佼佼者.大自然, 2005,3: 4-6.
3. Moore LG, Armaza F, Villena M, et a1. Comparative aspects of high-altitude adaptation in human populations. Adv Exp Med Biol, 2000, 475: 45-62.
4. Almeida AMedina JM. Isolation and characterization of tightly coupled mitochondria from neurons and astrocytes in primary culture. Brain Research, 1997,764: 167-172.
5. Huanq M, Camara AK, Stowe DF, et al. Mtochondrial inner membrane electrophysiology assessed by Rhodamine-123 transport and fluorescence. J. Ann Biomed Enq, 2007; 20: 1-2
6. Gasnier F, Rousson R, Lerme F, et al. Use of Percoll gradients for isolation of human placenta mitochondria suitable for investigating out membrane proteins. Anal Biochem, 1993, 212: 173-178.
7. Martinez F, Uribe A,Espinosa-Garcia MT, et al. Calcium modulates the ATP and ADP hydrolysis in human placental mitochondria. Int J Biochem Cell Biol, 2002, 34: 992-1003.
8. Wenchich L, Drahota Z, Honzik T, et al. Polarographic evaluation of mitochondrial enzymes activity in isolated mitochondria and in permeabilized human muscle cells with inherited mitochondrial defects. J. Physiol Res, 2003, 52:781-788.
9. Noji H, Yasuda R, Yoshida M, et al. Direct observation of the rotation of F1-ATPase. Nature, 1997, 386: 299-302.
10. 王谦,主编.现代医学实验方法,第一版,北京:人民卫生出版社, 1997,341-344
11. Tanabe M, Nishio K, Iko Y, et al. Rotation of a complex of the gamma subunit and c ring of Escherichia coli ATP synthase. The rotor and stator are interchangeable.J Biol Chem, 2001, 276: 15269-74.
12. 林秀来,刘良明,胡德耀.HAD 对创伤失血性休克大鼠肝细胞线粒体功能的保护作用.第三军医大学学报,2000, 22:439-441
13. Brustovetsky N, Brustovetsky T, Jemmerson R,et al. Calcium-induced cytochrome c release from CNS mitochondria is assiociated with the permeability transition and rupture of the outer membrane.J Neurochem,2002, 80: 207-18
14. Emaus RK, Grunwald R, Lemasters JJ. Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim Biophys Acta, 1986,850: 436-448
15. 高文祥,吴利平.急慢性缺氧对大鼠脑线粒体能量代谢的影响.中国病理生理杂志,2000,16:879-882
16. Kwast KE, Hand SC. Oxygen and Ph Regulation of protein synthesis in mitochondria from Artemia franciscana embryos. Biochem J,1996, 313: 207-13
17. Sch?nfeld P, Bohnensack R. Developmental changes of the adenine nucleotide translocation in rat brain. Biochim Biophys Acta, 1995, 1232: 75-80
18. Schonfeld P, Schild L, Bohnensack R. Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP + ADP) pool contribute to postnatal maturation of the rat heart. Eur J Biochem, 1996, 241: 895-900.
19. Chance Williams CM. Respiratory enzymes in oxidative phosphorylation: III. J Biol Chem 1955, 217:405–427.
20. Hartinger S, Tapia V, Carrillo C, et al. Birth weight at high altitudes in Peru. Int J Gynaecol Obstet, 2006, 93: 275-81.
21. 皮建辉, 吴亿中.新生儿体重、身长和体表面积的研究. 解剖科学进展, 2005, 11: 27-28.
22. Van de Sluis B, M uller P, Duran k, et al. Increased activity of hypoxia-inducible factor 1 is associated with early embryonic lethality in Commd1 null mice. J. Mol Cell Biol, 2007; 19: 1-2.
23. 高文祥, 高钰琪, 李素芝,等.缺氧对世居高原藏族人脐静脉内皮细胞 ET 和 NO水平的影响.中国应用生理学杂志, 2005, 21: 1-4.
24. Zamudio S, Wu Y, Letta F, et al. Human placental hypoxia-inducible factor-1 {alpha} expression correlates with clinical outcomes in choronic hypoxia in vivo. Am J Pathol, 2007, 19: 1-2.
25. Stock D, Gibbons C, Arechaqa I, et al. The rotary mechanism of ATP synthase. J. CurrOpin Struct Biol, 2000,10:672-679.
26. Yinqhao Z, Jun W, Yuanbo C, et al. Rotary torque produced by proton motive force in F0F1 motor. J. Biochem Biophys Res Commun, 2005, 331: 370-374.
27. Folger T, Torbakk N, Torbergsen T, et al. Mutations in mitochondrial transfer ribonucleic acid genes in preeclampsia. Am J Obstet Gynecol,1996,174:1626-1630.
28. Swierczynski J, Klimek J , Zelewski L.Correlation between the malate dependent progesterone and citrate biosynthesis in the mitochondrial fraction of human term placenta. The stimulatory effect of ADP and ATP .J Steroid Biochem, 1986,24(2):591-5.
29. Swierczynski J, Aleksandrowicz Z, Zelewski L. Stimulatory effect of ADP, ATP, NAD(P) on pyruvate production from malate by uncoupled human placental mitochondria. Biochem Med Metab Biol, 1987, 38: 156-64.
30. Murphy VE, Smith R, Giles WB. et al. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. J. Endocr Rev. 2006; 27: 141-169.
31. Cataldi A, Bianchi G, Rapino C.et al. Molecular and morphological modifications occurring in rat heart exposed to intermittent hypoxia: role for protein kinase C alpha. Exp Gerontol, 2004 ; 39:395-405.
32. 马正伟,汪仕良,王凤君等.缺氧条件下大鼠肝细胞糖酵解变化的实验研究.中华烧伤杂志,2002,18(4):238-241.
33. Zeng H, Saari JT, Johnson WT. Copper deficiency decreases complex IV but not complex I,II,III,or V in the mitochondrial respiratory chain in rat heart. J. Nutr, 2007, 137: 14-18.
34. Bianchi C, Genova ML,Parenti Castelli, et al. The mitochondrial respiratory chain is partially organized in a supercomplex assembly: kinetic evidence using flux control analysis. J Biol Chem ,2004, 279: 36562-36569
35. Dhar Mascareno M, Carcamo JM, Golde DW. Hypoxia-reoxygenation-induced mitochondrial damage and apoptosis in human endothelial cells are inhibited by vitamin C. Free Radic Biol Med, 2005,38:1311-1322.
36. Korge P, Honda HMWeiss JN. K+-dependent regulation of matrix volume improves mitochondrial function under conditions mimicking ischemia-reperfusion. Am J Physiol Heart Circ Physiol ,2005,289: 66-77.
37. Feldkamp T, Kribben AWeinberg JM. Assessment of mitochondrial membrane potential in proximal tubules after hypoxia-reoxygenation. Am J Physiol Renal Physiol,2005, 288: 1092 - 1102.
38. Niquet J, Liu H, Wasterlain CG. Programmed neuronal necrosis and status epilepticus. Epilepsia, 2005, 46: 43-48.
39. Rottenberg H, Koeppe RE. Stimulation of cation transport in mitochondria by gramicidin and truncated derivatives. Biochemistry, 1989, 28: 4361-4367.
40. Atkinson DE, Fall L. Adenosine triphosphate conservation in biosynthetic regulation. Escherichia coli phosphoribosylpyrophosphate synthase. J Biol Chem, 1967,242: 3241-3242.
41. 李兵.缺氧过程中大鼠心肌线粒体能量代谢和腺苷酸转位酶活性及表达的研究.第三军医大学学报, 2004:37-39.
42. 刘金彪, 陈登庭, 杨国宗, 等.急性胰腺炎时大鼠肝脏能量代谢变化的实验研究.洛阳医专学报,1999,3:34-35.
43. Wynn JP, Hamid AA, Li Y, et al. Biochemical events leading to the diversion of carboninto storage lipids in the oleaginous fungi Mucor circinelloides and Mortierella alpina. Microbiology, 2001,147: 2857-2864.
1. Lombardi A, Silvestri E, Moreno M,et al. Skeletal muscle mitochondrial free-fatty-acid content and membrane potential sensitivity in different thyroid states:involvement of uncoupling protein-3 and adenine nucleotide translocase. FEBS-Lett. 2002 4; 532:12-16.
2. Kaukonen J, Juselius JK, Tiranti V,et al. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science, 2000, 289: 782-785.
3. Kopustinskiene DM, Toleikis A and Saris NE. Adenine nucleotide tranlocase mediates the K(ATP)-channel-openers-induced proton and potassium flux to the mitochondrial matrix. J Bioenerg Biomembr, 2003, 35: 141-148.
4. 高文祥, 柳君泽, 吴利平等. 低氧大鼠脑线粒体体外转录活性的研究. 中国营养生理学杂志, 2001, 17: 323-326
5. Pipinos II, Sharov VG, Shepard AD, et al. Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease.J Vasc Surg, 2003, 38: 827-832.
6. Sch?nfeld P, Bohnensack R. Developmental changes of the adenine nucleotide translocation in rat brain. Biochim Biophys Acta, 1995, 1232: 75-80.
7. Schonfeld P, Schild L, Bohnensack R. Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP + ADP) pool contribute to postnatal maturation of the rat heart. Eur J Biochem, 1996, 241: 895-900.
8. Florian A, Sch?nfeld P. Alteration of the ADP/ATP translocase isform pattern improves ATP expenditure in developing rat liver mitochondria. FEBES Letters, 1998, 433: 261-264.
9. 萨姆布鲁克 J, 拉塞尔 D.W. 分子克隆实验指南.第三版.北京.科学出版社, 2002, 516-701.
10.Ciapaite J, Bakker SJ, Van Eikenhorst G. et al. Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats.Biochim Biophys Acta,2007, 1772:307-16.
11. Dahout-Gonzalez C, Nury H, Trezequet V, et al. Molecular, functional, and pathologicalaspects of the mitochondrial ADP/ATP carrier. Physiology, 2006, 21:242-249
12. Nury H, Dahout-Gonzalez C, Trezequet V, et al. Relations between structure and function of the mitochondrial ADP/ATP carrier. Annu Rev Biochem, 2006, 75:713-741.
13. Vyssokikh MY, Katz A, Rueck A,et al. Biochem-J. Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophilin D.2001, 358: 349-358.
14. Dolce A, Scarcia P, Iacopetta D, et al. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Letters, 2005, 579: 633-637.
15.Truscott KN, Wiedemann N, Rehling P,et al. Mitochondrial import of the ADP/ATP carrier:the essential TIM complex of the intermembrane space is required for precursor release from the TOM complex. Mol-Cell-Biol, 2002, 22: 7780-7789.
16. Muhlenbein N, Hofmann S, Rothbarer U,et al. Organization and function of the small Tim complexes acting along the import pathway of metabolite carriers into mammalian mitochondria. J Biol Chem, 2004, 279: 13540-13546.
17. Frazier AE, Chacinska A, Truscott KN. et al. Mitochondria use different mechanisms for transport of multispanning membrane proteins through the intermembrane space. Mol Cell Biol., 2003; 23:7818-7828.
18. Passarella S, Ostuni A, Atlante A, et al. Increase in the ADP/ATP exchange in rat liver mitochondria irradiated in vitro by helium-neon laser. Biochem Biophys Res Commun, 1988, 156: 978-986
19. Motoyama S, Saiti S, Munamiya, et al. Methylprednisolone inhibits low-flow hypoxia-induced mitochondrial dysfunction in isolated perfused rat liver. Crit Care Med, 2003, 31: 1468-1474.
20. Morikawa N, Suematsu M, Kyokane T, et al. Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver. Hepatology, 1998, 28: 1289-1299.
21. Irwin WA, Gaspers LD, Thomas JA. Inhibition of the mitochondrial permeability transition by aldehydes. Biochem Biophys Res Commun, 2002, 291: 215-219.
22. Khan S, O Brien PJ. Modulating hypoxia-induced hepatocyte injury by affectingintracellular redox state. Biochim Biophys Acta, 1995, 1269: 153-161.
23. Casey TM, Pakay JL, Guppy M, et al. Hypoxia causes downregulation of protein and RNA synthesis in noncontracting Mammalian cardiomyocytes. Circ-Res, 2002, 90: 777-783.
24. Gnaiger E, Mendez G, Hand SC. High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci USA, 2000, 97: 11080-11085.
1. Dahout-Gonzalez C, Nury H, Trezeguet V. et al. Molecular, functional, and pathological aspects of the mitochondrial ADP/ATP carrier. Physiology, 2006, 21:242-249.
2. Eva Pebay-Peyroula and Ge′ rard Brandolin Nucleotide exchange in mitochondria: insight at a molecular level. Current Opinion in Structural Biology, 2004, 14: 420–425
3. Edmund R.S. Kunji.The role and structure of mitochondrial carriers FEBS Letters, 2004, 564: 239-244
4. Dahout-Gonzalez C, Ramus C, Dassa EP. et al. Conformation-dependent swinging of the matrix loop m2 of the mitochondrial Saccharomyces cerevisiae ADP/ATP carrier.Biochemistry, 2005, 44(49):16310-20.
5. Satoru Goto,Hiroshi Chuman.How does the mitochondrial ADP/ATP carrier distinguish transportableATP and ADP from untransportable AMP and GTP? Dynamic modeling of the recognition/ translocation process in the major substrate binding region.J Biochimica et Biophysica Acta, 2002, 1589: 203-218.
6. Robinson AJ, Kunji ER. Mitochondrial carrier in the cytoplasmic state have a common substrate binding site.J.Proc Natl Acad Sci U S A, 2006, 103: 2617-2622.
7. Dyall SD,A gius SC, et al..The dynamic dimerization of the yeast ADP/ATP carrier in the inner mitochondrial membrane is affected by conserved cysteine residued. J-Biol-Chem, 2003, 278: 26757-26764.
8. Huang SG, Odoy S and Klimberg M. Chimers of two fused ADP/ATPcarrier monomers indicate a single channel for ADP/ATP transport .Arch-Biochem-Biophys. 2001, 394: 67-75
9. Itoi S, Misaki R, Hirayama M. et al. Identification of three isoforms for mitochondrial adenine nucleotide translocator in the pufferfish Takifugu rubripes. Mitochondrion. 2005, 5(3):162-72.
10. Dolce V, Scarcia P, Iacopetta D, Palmieri F. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Lett, 2005, 579: 633-637.
11. Mikahil Yu VYSSOKIKH,Annette KATZ,Alexander RUECK,Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophillin D. J. Biochem, 2003, 358:349-358
12. Naoshi Yamazaki, Yasuo Shinohara. Structural properties of mammalian mitochondrial ADP/ATPcarriers: identification of possible amino acids that determine functional differences in its isoforms J. Mitochondrion, 2002, 1: 371–379
13. Siekevitz PV,Potter VR. Biochemical structure of mitochondrial intramitochondrial components and oxidative phosphorylation.J. Biol Chem. 1995 ,215: 237-255
14. Pressman BC.Intramitochondrial nueleotides.1.Some factors affecting net interconversion of adenine nucleotides.J Biol Chem.1958,232: 967-978
15. Bruni A.Contessa AR,Lueuni S.Atractyloside as inhibitor of energy-transfer reactions in liver mitochondria.J Biochim Biophys Acta.1962, 60:301-316
16. Kemp A,Slater EC.The site of action of atractyloside.Biochim Biophys Acta. 1964, 92:178-180
17. Vignais PV,Vignais PM,Stanislas EAction of potassium atractyloside on oxidative phosphorylation in mitochondria and submitochondrial particles.J Biochim Biophys Acta. 1962, 60:284-300
18. Chappel JB,Crofts AR.The effect of atractyloside and oligomycin on the behavior of mitochondria towards the adenine nucleotides. J Biochem, 1965, 95:707-716
19. Heldt HW, Jacobs H, Klingenberg M. Endogenous ADP of mitochondria, an early phosphate acceptor of oxydative phosphorylationas disclosed by kinetic studies with
14C-labeled ADP and ATP and with atractyloside. Biochem Biophys Res Common, 1965, 18: 174-179
20. Dalia M.Kopustinskiene,Adenine Nuleotide Translocase Mediates the KATP- Channel- Openers-Induced Proton and Potassium Flux to the Mitochodrial Matrix. Jjournal of Bioenergetics and Biomembranes, 2003, 35: 141-148.
21. Kowaltowski AJ, Seetharaman S, Paucek P, Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria. Am J Physiol Heart Circ Physiol. 2001, 280: 649-657.
22. Krolikowski JG, Bienengraeber M, Weihrauch D. et al. Inhibition of mitochondrialpermeability transition enhances isoflurane-induced cardioprotection during early reperfusion: the role of mitochondrial KATP channels.Anesth Analg. 2005, 101(6): 1590-1596.
23. Lipskaya TY, Savchenko MS. Once again about the functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase. Biochemistry (Mosc), 2003, 68:68-79.
24. Pasdois P, Quinlan CL, Rissa A. et al. Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS.Am J Physiol Heart Circ Physiol, 2007, 292(3):1470-1478.
25. Graham BH, Waymine KG, Cottrell B, Trounce IA, MacGregorGR, Wallace DC. A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heartrmuscle isoform of the adenine nucleotide translocator.Nat Genet, 1997, 16:226–34.
26. Mckenzie M, Liolitsa D, Hanna MG..et al.Mitochondrial disease: mutations and mechanisms. Neurochem Res, 2004, 29(3):589-600.
27. Belen Notario,Csrlos Manchado.Assessment of Membrane-Bound Mammal Mitochondrial Adenine Nucleotide Translocase Topography by Experimental Antibodies. Biochemistry, 2003, 42: 820-828.
28. Christelle Fiore, Delphine Arlot-Guilliga. Fluorometric detection of ADP /ATP carrier deficiency in human muscle J. Clinica Chimica Acta, 2001, 311: 125–135
29. A.Lombardia, E. Silvestrib, M.Skeletal muscle mitochondrial free-fatty-acid content and membrane potential sensitivity in different thyroid states: involvement of uncoupling protein-3 and adenine nucleotide translocase. FEBS Letters, 2002, 532: 12-16
30. Ventura FV, Tavares de Almeida I,Wanders RJ, et al. Inhibition of adenine nucleotide transport in rat liver mitochondria by long-chain acyl-coenzyme A beta-oxidation intermediates. Biochem Biophys Res Commun, 2007, 352: 873-878.
31. Kaukonen J, Zeviani M, Comi GP, Piscaglia MG, Peltonen L, Suomalainen A. A third locus predisposing to multiple deletions of mtDNA in autosomal dominant progressive external ophthalmoplegia. Am J Hum Genet, 1999, 65: 256–61.
32. Kaukonen J, Juselius JK, Tiranti V, et al. Role of adenine nucleotide translocator 1 inmtDNA maintenance. Science, 2000, 289: 782–785.
33. Fiore, C., Trezeguet, V., Le Saux, A., The mitochondrial ADP/ATP carrier: structural, physiological and pathological aspects. Biochimie, 1998, 80: 137–150.
34. Vyssokikh, M.Y., Brdiczka, D., The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis.Acta Biochim. Pol, 2003, 50: 389–404.
35. Crompton,M.,Virji,S.and Ward,J.M. Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine mucleotide translocase to form the permeability transition pore. Eur. J. Biochem, 1998, 258:729-735
36. Susin,S.A, Lorenzo,H.K. Snow,B.E. etal. Molecular characterisation of mitochondrial apoptosis-ducing facter. Nature, 1999, 397: 441-446
37. Garcia N, Maartinez-Abundis E, Pavon N, et al. Copper induces permeability transition through its interaction with the adenine nucleotide translocase. Cell Biol Int, 2007, 25: 1-2
38. Belzacq, A.S., Vieira, H.L., Verrier, F., Bcl-2 and Bax modulate adeninenucleotide translocase activity. Cancer Res, 2003, 63: 541–546.
39. Baucer,M.K.,Rocks,O.and Grimm,S. Adenine nucleotide translocase-1,a component of the permeability transition pore can dominantly induce apoptosis,J.ell Biol, 1999, 147: 1493-1502
40. Mo'nica Zamora, Meritxell Granell. Adenine nucleotide translocase 3 (ANT3) overexpression inducesapoptosis in cultured cells .FEBS Letters, 2004, 563: 155-160
41. Kokoszka JE, Waymire KG, Levy SE,The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature, 2004, 427: 461-465
1. GonzalesGF, GonezC, VillenaAetal. Adreno pause or decline of serum adrenal androgens with age in women living at sea level or at high altitude. J.Endocrinol, 2002, 173(1):95.
2. Vitzthum V J, Ellison PT, Sukalich S, et al. Does hypoxia impair ovarian function in Bolivian women indigenous to high altitude? High Alt Med Biol, 2000, 1(1): 39
3. Escudero F, Gonzales GF, Gonez C. Hormone profile during the menstrual cycle at high altitude. Int J Gynaecol Obstet, 1996, 55(1): 49
4. Sobrevilla LA, Romero I, Kruger F. et al.Low estrogen excretion during pregnancy at high altitude. Am J Obstet Gynecol, 1968, 102(6):828.
5. Zamudio S, Leslie KK,White M. et al. Low serum estradiol and high serum progesterone concentrations characterize hypertensive pregnancies at high altitude. J Soc Gynecol Investig, 1994, 1(3):197.
6. Rhee JW, Longo LD, Pearce WJ. et al. Effect of chronic hypoxia on myometrial responsiveness in the pregnant rat. Am J Physiol, 1996, 270(3): 477
7. Macome JC, Costa LE, Martin IH. et al. Steroid biosythesis by gonads of rat submitted to chronic hypobaric hypoxia. Acta Physiol-Lat-Am, 1977, 27(5): 249.
8. Krebs C, Macara LM, Leiser R, Bowman AW. Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilicl artery is associated with maldevelopment of the placental terminal villous tree.Am J Obstet Gynecol, 1996, 1534-1542.
9. Jansson T, Ekstrand Y, Bjorn C, Wennergren M. Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes, 2002, 51: 2214-2219.
10. McMullen S, Osgerby JC, Thurston LM, Gadd TS. Alterations in placental 11beta-hydroxysteroid dehydrogenase activities and fetal cortisol:cortisone ratios induced by nutritional restriction prior to conception and at defined stages of gestation in ewes. Reproduction 2004, 127: 717-725.
11. Vonnahme KA, Ford SP. Differential expression of the vascular endothelial growth factor-receptor system in the gravid uterus of Yorkshire and Meishan pigs.Bio Reprod, 2004, 71: 163-169.
12. Wallace JM, Aitken RP, Milne JS. Nutritionally mediated placental growth factor-receptor system in the growing adolescent:consequences for the fetus.Biol Reprod 2004, 71: 1055-1062.
13. Jansson T, Ekstrand Y, Bjorn C, Wennergren M.Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes, 2002, 51: 2214-2219.
14. Jansson T, Wennergren M, Powell TL. Placental glucose transport and GLUT1 expression in insulin-dependent diabetes.Am J Obstet Gynecol, 1999, 180: 163- 168.
15. Gansson N, Greenwood SL, Johansson BR, Powell TL. Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments.J Clin Endocrinol Metab 2003, 88:1205-1211.
16. JanssonT, PowellTL. Placental nutrient transfer and fetal growth. Nutrition, 2000, 16: 500-502.
17. Mahendran D, Donnai P, Glazier JD. Amino acid(system A)transporter activity in microvillous membrane vesicles from the placentas of appropriate and small for gestational age babies.Pediatr Res,1993, 34:661-665.
18. Jasson T,Scholtbach V,Powell TL.Placental transport of leucine and lysine is reduced in intrauterine growth restriction.Pediatr Res,1998, 157:2111-2122.
19. Ayuk PT, Theophanous D, D’Souza SW. 1-arginine transport by the microvillous plasma membrane of the syncytiotrophobast from human placenta in relation to nitric oxide production:effects of gestation,preeclampsia,and intrauterine growth restriction.J Clin Endocrinol Metab,2002, 87:747-751.
20. Godfrey KM. Maternal regulation of fetal development and health in adult life.Eur J Obstet Gynecol Reprod Biol,1998, 78:141-150.
21. Nelson DM, Smith SD, Furesz TC. Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts.Am J Physiol Cell Physiol, 2003, 284: 310-315.
22. Cramer S, Beveridge M, Kilberg M. Physiological importance of system A-mediated amino acid transport to rat fetal development.Am J Physiol Cell Physiol, 2002, 282: 153-160.
23. Sibley CP, Coan PM, Ferguson-Smith AC. Placental-specific insulin-like growth factor2IIgf2)regulates the diffusional exchange characteristics of the mouse placenta.Proc Natl Acad Sci USA, 2004, 101: 8204-8208.
24. Lindsay RS, Lindsay RM, Waddell BJ. Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat:studies with the 11 beta-hydroxysteroid dehydrogenase inhibito carbenoxolone. Diabetologia, 1996, 39: 1299-1305.
25. Welberg LA, Seckl JR, Holmes MC. Inhibition of 11beta-hydroxysteroid dehydrogenase the foeto-placental barrier to maternal glucocorticoids,permanently programs amygdale GR mRNA expression and anxiery-like behaviour in the offspring. Eur J Neurosci, 2000, 12: 1047-1054.
26. Krozowski Z, MaGuire JA, Stein-Oakley AN. Immunohistochemical localization of the 11-beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta.J Clin Endocrinol Metab, 1995, 80: 2203-2209.
27. Sechl FR, Cleasby M, Nyirenda MF. Glucocorticoids,11beta- hydroxysteroid dehydrogenase and fetal programming. Kidney Int, 2000, 57: 1412-1417.
28. Murphy VE,Clifton VL.Alterations in human placental 11-beta- hydroxysteroid dehydrogenase type1 and 2 with gestational age and labour. Placenta, 2003, 24: 739-744.
29. Alfaidy N, Gupta S, DeMarco C. Oxygen regulation of placental 11 beta- hydroxysteroid dehydrogenase 2:physiological and pathological implications.J Clin Endocrinol Metab, 2002, 87, 4797-4805.
30. Challis JR, Sloboda DM, Alfaidy N. Prostaglandins and mechanisms of preterm birth. Reproduction 2002, 124:1-17.
31. McMullen S, Osgerby JC, Thurston LM. Alterations in placental 11 beta- hydroxysteroid dehydrogenase (11 betaHSD)activities and fetal cortisol:cortisone ratios induced by nutritional restriction prior to conception and at defined stages of gestation in ewes. Reproduction, 2004, 127: 717-725.
32. Genbacev O, Zhou Y, Ludlow JW. Regulation of human placental development by oxygen tension. Science, 1997, 277: 1669-1672.
33. Burton GJ, Hempstoch J, Jauniaux E. Nutrition of the human fetus during the first trimester-a review. Placenta, 2001, 22: 70-77
34. Jauniaux E, Watson AL, Hempstoch J. Onset of maternal arterial blood flow and placental oxidative stress.A possible factor in human early pregnancy failure.Am J Pathol, 2000, 157: 2111-2122.
35. Padavala S, Pope N, Baker P, et al. An imbalance between vascular endothelial growth factor and its soluble receptor in placental villous explants of intrauterine growth-restricted pregnancies. J Soc Gynecol Investig, 2006, 13: 40-47.
36. Charnock-Jones DS, Kaufmann P, Mayhew TM. Aspects of human fetoplacental vasculogenesis and angiogenesis.I. Molecular regulation. Placenta,2004, 25: 103- 113.
37. Son SM. Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes.Diabetes Res Clin Pract. 2007, 26: 1-2.
38. Atamer Y, Kocyigit Y, Yokus B, et al. Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia.Eur J Obstet Gynecol Reprod Biol, 2005, 119: 60-66.
39. Cui XL, Brockman D, Campos B, Myatt L. Expression of NADPH oxidase isoform 1(Nox1)in human placenta:involvement in preeclampsia. Placenta, 2006, 27: 422-431.
40. Webster RP, Brockman D, Myatt L. et al. Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia. J. Mol Hum Reprod. 2006, 12:677-685.
41. Kossenjans W, Eis A, Aahay R. Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia.Am J Physiol Heart Circ Physiol, 2000, 278: 1311-1319.
42. Mudgett JS, Ding J, Guh-Siesel L, Chartrain NA. Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis.Proc Natl Acad Sci USA, 2000, 97: 10454-10459.
43. Zamudio S, Kovalenko O, Vanderlelie J. et al. Chronic Hypoxia In Vivo ReducesPlacental Oxidative Stress. Placenta. 2007, 7,
44. Zamudio S. High-altitude hypoxia and preeclampsia.Front Biosci. 2007, 12:2967-2977.
2. 吴天一. 藏族——高原适应的佼佼者. 大自然, 2005,3:4-6.
3. More LG, Zamudio S, Jorde LB, el a1. 高原遗传性适应. 西藏医药杂志, 1997, 8: 6-15.
4. 高文祥, 柳君泽, 吴利平, 等. 急、慢性缺氧对大鼠脑线粒体能量代谢的影响. 中国病理生理学杂志, 2000,16:879-882.
5. Zharova TV, Vinogradov AD. Energy-linked binding of Pi is required for continuous steady-state proton-translocating ATP hydrolysis catalyzed by F0.F1-ATP synthase. Biochemistry, 2006, 45(48):14552-14558.
6. Nury H, Dahout-Gonzalez C, Trezequet V, et al. Relations between structure and function of the mitochondrial ADP/ATP carrier. Annu Rev Biochem, 2006, 75:713-741.
7. Vyssokikh MY, Katz A, Rueck A,et al. Biochem-J. Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophilin D.2001, 358: 349-358.
8. Dolce A, Scarcia P, Iacopetta D, et al. A fourth ADP/ATP carrier isoform in man: identification, bacterial, expression, functional characterization and tissue distribution. FEBS Letters, 2005, 579: 633-637.
9. Voos W, Martin H, Krimmer T, et al. Mechanisms of protein translocation into mitochondria. Biochim Biophys Acta, 1999, 1422(3): 235-254.
10. Peter Gluckman , Mark Hanson.The Fetal Matrix Evolution,Development and Disease[M]. Cambridge University Press, 2005, 257.
11. Lawlor DA,Ronalds G. Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s:findings from the Aberdeen Children of the 1950s prospective cohort study [J]. Circulation, 2005, 6(10): 1414-1418.
12. Lawlor DA, Ebrahim S.Association of birth weight with adult lung function:findings from the British Women’s Heart and Health Study and a meta-analysis [J]. Thorax, 2005, 60(10): 851-858.
13. Wu TY, Tu DT, Zhau GL, etal. The physiological differences between the Tietans and the Andeans.In:OhnoH,KobayashiT,Masuyama Sand NakashimaM(eds), Progress of Mountain Medicine and HighAltitude Physology [J] . SMM, Tokorozawa, Matsumoto, 1998, 190~194.
14. Adair FL, Thelander H. A study of the weight and dimensions of the human placenta in its relation to the weight of the newborn infant [J] . Am J Obstet Gynecol, 1925, 10: 172– 205.
15. Adair FL, Thelander H. A study of the weight and dimensions of the human placenta in its relation to the weight of the newborn infant[J]. Am J Obstet Gynecol,1925,10:172– 205.
16. 王军,王志农,李素芝,等.拉萨市6500名小学生先天性心脏病调查[J].西藏科技,2002,(1):12-14
17. ZamudioS. The placenta at high altitude[J]. High Alt Med Biol,2003,4(2):171-191.
18. Moore LG, Shriver M, Bemis L, et al. Maternal adaptation to high-altitude pregnancy :an experiment of nature —a review [J]. Placenta, 2004, 25(suppl A):60– 71.
19. Fionnuala Mc Auliffe, Nikos Kametas, Elisabeth Krampl. Blood gases in pregnancy at sea level and at high altitude [J].British Journal of Obstetrics and Gynaecology, 2001, 108(9): 980-985.
20. Mortola JP, Frapell PB, Agqero L, et al. Birth weight and altitude: a study in Peruvian communities [J]. Peadiatr, 2000, 136(33):324–329.
1. More LG, Zamudio S, Jorde LB, el a1. 高原遗传性适应. 西藏医药杂志, 1997, 8: 6-15.
2. 吴天一.藏族——高原适应的佼佼者.大自然, 2005,3: 4-6.
3. Moore LG, Armaza F, Villena M, et a1. Comparative aspects of high-altitude adaptation in human populations. Adv Exp Med Biol, 2000, 475: 45-62.
4. Almeida AMedina JM. Isolation and characterization of tightly coupled mitochondria from neurons and astrocytes in primary culture. Brain Research, 1997,764: 167-172.
5. Huanq M, Camara AK, Stowe DF, et al. Mtochondrial inner membrane electrophysiology assessed by Rhodamine-123 transport and fluorescence. J. Ann Biomed Enq, 2007; 20: 1-2
6. Gasnier F, Rousson R, Lerme F, et al. Use of Percoll gradients for isolation of human placenta mitochondria suitable for investigating out membrane proteins. Anal Biochem, 1993, 212: 173-178.
7. Martinez F, Uribe A,Espinosa-Garcia MT, et al. Calcium modulates the ATP and ADP hydrolysis in human placental mitochondria. Int J Biochem Cell Biol, 2002, 34: 992-1003.
8. Wenchich L, Drahota Z, Honzik T, et al. Polarographic evaluation of mitochondrial enzymes activity in isolated mitochondria and in permeabilized human muscle cells with inherited mitochondrial defects. J. Physiol Res, 2003, 52:781-788.
9. Noji H, Yasuda R, Yoshida M, et al. Direct observation of the rotation of F1-ATPase. Nature, 1997, 386: 299-302.
10. 王谦,主编.现代医学实验方法,第一版,北京:人民卫生出版社, 1997,341-344
11. Tanabe M, Nishio K, Iko Y, et al. Rotation of a complex of the gamma subunit and c ring of Escherichia coli ATP synthase. The rotor and stator are interchangeable.J Biol Chem, 2001, 276: 15269-74.
12. 林秀来,刘良明,胡德耀.HAD 对创伤失血性休克大鼠肝细胞线粒体功能的保护作用.第三军医大学学报,2000, 22:439-441
13. Brustovetsky N, Brustovetsky T, Jemmerson R,et al. Calcium-induced cytochrome c release from CNS mitochondria is assiociated with the permeability transition and rupture of the outer membrane.J Neurochem,2002, 80: 207-18
14. Emaus RK, Grunwald R, Lemasters JJ. Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim Biophys Acta, 1986,850: 436-448
15. 高文祥,吴利平.急慢性缺氧对大鼠脑线粒体能量代谢的影响.中国病理生理杂志,2000,16:879-882
16. Kwast KE, Hand SC. Oxygen and Ph Regulation of protein synthesis in mitochondria from Artemia franciscana embryos. Biochem J,1996, 313: 207-13
17. Sch?nfeld P, Bohnensack R. Developmental changes of the adenine nucleotide translocation in rat brain. Biochim Biophys Acta, 1995, 1232: 75-80
18. Schonfeld P, Schild L, Bohnensack R. Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP + ADP) pool contribute to postnatal maturation of the rat heart. Eur J Biochem, 1996, 241: 895-900.
19. Chance Williams CM. Respiratory enzymes in oxidative phosphorylation: III. J Biol Chem 1955, 217:405–427.
20. Hartinger S, Tapia V, Carrillo C, et al. Birth weight at high altitudes in Peru. Int J Gynaecol Obstet, 2006, 93: 275-81.
21. 皮建辉, 吴亿中.新生儿体重、身长和体表面积的研究. 解剖科学进展, 2005, 11: 27-28.
22. Van de Sluis B, M uller P, Duran k, et al. Increased activity of hypoxia-inducible factor 1 is associated with early embryonic lethality in Commd1 null mice. J. Mol Cell Biol, 2007; 19: 1-2.
23. 高文祥, 高钰琪, 李素芝,等.缺氧对世居高原藏族人脐静脉内皮细胞 ET 和 NO水平的影响.中国应用生理学杂志, 2005, 21: 1-4.
24. Zamudio S, Wu Y, Letta F, et al. Human placental hypoxia-inducible factor-1 {alpha} expression correlates with clinical outcomes in choronic hypoxia in vivo. Am J Pathol, 2007, 19: 1-2.
25. Stock D, Gibbons C, Arechaqa I, et al. The rotary mechanism of ATP synthase. J. CurrOpin Struct Biol, 2000,10:672-679.
26. Yinqhao Z, Jun W, Yuanbo C, et al. Rotary torque produced by proton motive force in F0F1 motor. J. Biochem Biophys Res Commun, 2005, 331: 370-374.
27. Folger T, Torbakk N, Torbergsen T, et al. Mutations in mitochondrial transfer ribonucleic acid genes in preeclampsia. Am J Obstet Gynecol,1996,174:1626-1630.
28. Swierczynski J, Klimek J , Zelewski L.Correlation between the malate dependent progesterone and citrate biosynthesis in the mitochondrial fraction of human term placenta. The stimulatory effect of ADP and ATP .J Steroid Biochem, 1986,24(2):591-5.
29. Swierczynski J, Aleksandrowicz Z, Zelewski L. Stimulatory effect of ADP, ATP, NAD(P) on pyruvate production from malate by uncoupled human placental mitochondria. Biochem Med Metab Biol, 1987, 38: 156-64.
30. Murphy VE, Smith R, Giles WB. et al. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. J. Endocr Rev. 2006; 27: 141-169.
31. Cataldi A, Bianchi G, Rapino C.et al. Molecular and morphological modifications occurring in rat heart exposed to intermittent hypoxia: role for protein kinase C alpha. Exp Gerontol, 2004 ; 39:395-405.
32. 马正伟,汪仕良,王凤君等.缺氧条件下大鼠肝细胞糖酵解变化的实验研究.中华烧伤杂志,2002,18(4):238-241.
33. Zeng H, Saari JT, Johnson WT. Copper deficiency decreases complex IV but not complex I,II,III,or V in the mitochondrial respiratory chain in rat heart. J. Nutr, 2007, 137: 14-18.
34. Bianchi C, Genova ML,Parenti Castelli, et al. The mitochondrial respiratory chain is partially organized in a supercomplex assembly: kinetic evidence using flux control analysis. J Biol Chem ,2004, 279: 36562-36569
35. Dhar Mascareno M, Carcamo JM, Golde DW. Hypoxia-reoxygenation-induced mitochondrial damage and apoptosis in human endothelial cells are inhibited by vitamin C. Free Radic Biol Med, 2005,38:1311-1322.
36. Korge P, Honda HMWeiss JN. K+-dependent regulation of matrix volume improves mitochondrial function under conditions mimicking ischemia-reperfusion. Am J Physiol Heart Circ Physiol ,2005,289: 66-77.
37. Feldkamp T, Kribben AWeinberg JM. Assessment of mitochondrial membrane potential in proximal tubules after hypoxia-reoxygenation. Am J Physiol Renal Physiol,2005, 288: 1092 - 1102.
38. Niquet J, Liu H, Wasterlain CG. Programmed neuronal necrosis and status epilepticus. Epilepsia, 2005, 46: 43-48.
39. Rottenberg H, Koeppe RE. Stimulation of cation transport in mitochondria by gramicidin and truncated derivatives. Biochemistry, 1989, 28: 4361-4367.
40. Atkinson DE, Fall L. Adenosine triphosphate conservation in biosynthetic regulation. Escherichia coli phosphoribosylpyrophosphate synthase. J Biol Chem, 1967,242: 3241-3242.
41. 李兵.缺氧过程中大鼠心肌线粒体能量代谢和腺苷酸转位酶活性及表达的研究.第三军医大学学报, 2004:37-39.
42. 刘金彪, 陈登庭, 杨国宗, 等.急性胰腺炎时大鼠肝脏能量代谢变化的实验研究.洛阳医专学报,1999,3:34-35.
43. Wynn JP, Hamid AA, Li Y, et al. Biochemical events leading to the diversion of carboninto storage lipids in the oleaginous fungi Mucor circinelloides and Mortierella alpina. Microbiology, 2001,147: 2857-2864.
1. Lombardi A, Silvestri E, Moreno M,et al. Skeletal muscle mitochondrial free-fatty-acid content and membrane potential sensitivity in different thyroid states:involvement of uncoupling protein-3 and adenine nucleotide translocase. FEBS-Lett. 2002 4; 532:12-16.
2. Kaukonen J, Juselius JK, Tiranti V,et al. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science, 2000, 289: 782-785.
3. Kopustinskiene DM, Toleikis A and Saris NE. Adenine nucleotide tranlocase mediates the K(ATP)-channel-openers-induced proton and potassium flux to the mitochondrial matrix. J Bioenerg Biomembr, 2003, 35: 141-148.
4. 高文祥, 柳君泽, 吴利平等. 低氧大鼠脑线粒体体外转录活性的研究. 中国营养生理学杂志, 2001, 17: 323-326
5. Pipinos II, Sharov VG, Shepard AD, et al. Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease.J Vasc Surg, 2003, 38: 827-832.
6. Sch?nfeld P, Bohnensack R. Developmental changes of the adenine nucleotide translocation in rat brain. Biochim Biophys Acta, 1995, 1232: 75-80.
7. Schonfeld P, Schild L, Bohnensack R. Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP + ADP) pool contribute to postnatal maturation of the rat heart. Eur J Biochem, 1996, 241: 895-900.
8. Florian A, Sch?nfeld P. Alteration of the ADP/ATP translocase isform pattern improves ATP expenditure in developing rat liver mitochondria. FEBES Letters, 1998, 433: 261-264.
9. 萨姆布鲁克 J, 拉塞尔 D.W. 分子克隆实验指南.第三版.北京.科学出版社, 2002, 516-701.
10.Ciapaite J, Bakker SJ, Van Eikenhorst G. et al. Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats.Biochim Biophys Acta,2007, 1772:307-16.
11. Dahout-Gonzalez C, Nury H, Trezequet V, et al. Molecular, functional, and pathologicalaspects of the mitochondrial ADP/ATP carrier. Physiology, 2006, 21:242-249
12. Nury H, Dahout-Gonzalez C, Trezequet V, et al. Relations between structure and function of the mitochondrial ADP/ATP carrier. Annu Rev Biochem, 2006, 75:713-741.
13. Vyssokikh MY, Katz A, Rueck A,et al. Biochem-J. Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophilin D.2001, 358: 349-358.
14. Dolce A, Scarcia P, Iacopetta D, et al. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Letters, 2005, 579: 633-637.
15.Truscott KN, Wiedemann N, Rehling P,et al. Mitochondrial import of the ADP/ATP carrier:the essential TIM complex of the intermembrane space is required for precursor release from the TOM complex. Mol-Cell-Biol, 2002, 22: 7780-7789.
16. Muhlenbein N, Hofmann S, Rothbarer U,et al. Organization and function of the small Tim complexes acting along the import pathway of metabolite carriers into mammalian mitochondria. J Biol Chem, 2004, 279: 13540-13546.
17. Frazier AE, Chacinska A, Truscott KN. et al. Mitochondria use different mechanisms for transport of multispanning membrane proteins through the intermembrane space. Mol Cell Biol., 2003; 23:7818-7828.
18. Passarella S, Ostuni A, Atlante A, et al. Increase in the ADP/ATP exchange in rat liver mitochondria irradiated in vitro by helium-neon laser. Biochem Biophys Res Commun, 1988, 156: 978-986
19. Motoyama S, Saiti S, Munamiya, et al. Methylprednisolone inhibits low-flow hypoxia-induced mitochondrial dysfunction in isolated perfused rat liver. Crit Care Med, 2003, 31: 1468-1474.
20. Morikawa N, Suematsu M, Kyokane T, et al. Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver. Hepatology, 1998, 28: 1289-1299.
21. Irwin WA, Gaspers LD, Thomas JA. Inhibition of the mitochondrial permeability transition by aldehydes. Biochem Biophys Res Commun, 2002, 291: 215-219.
22. Khan S, O Brien PJ. Modulating hypoxia-induced hepatocyte injury by affectingintracellular redox state. Biochim Biophys Acta, 1995, 1269: 153-161.
23. Casey TM, Pakay JL, Guppy M, et al. Hypoxia causes downregulation of protein and RNA synthesis in noncontracting Mammalian cardiomyocytes. Circ-Res, 2002, 90: 777-783.
24. Gnaiger E, Mendez G, Hand SC. High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci USA, 2000, 97: 11080-11085.
1. Dahout-Gonzalez C, Nury H, Trezeguet V. et al. Molecular, functional, and pathological aspects of the mitochondrial ADP/ATP carrier. Physiology, 2006, 21:242-249.
2. Eva Pebay-Peyroula and Ge′ rard Brandolin Nucleotide exchange in mitochondria: insight at a molecular level. Current Opinion in Structural Biology, 2004, 14: 420–425
3. Edmund R.S. Kunji.The role and structure of mitochondrial carriers FEBS Letters, 2004, 564: 239-244
4. Dahout-Gonzalez C, Ramus C, Dassa EP. et al. Conformation-dependent swinging of the matrix loop m2 of the mitochondrial Saccharomyces cerevisiae ADP/ATP carrier.Biochemistry, 2005, 44(49):16310-20.
5. Satoru Goto,Hiroshi Chuman.How does the mitochondrial ADP/ATP carrier distinguish transportableATP and ADP from untransportable AMP and GTP? Dynamic modeling of the recognition/ translocation process in the major substrate binding region.J Biochimica et Biophysica Acta, 2002, 1589: 203-218.
6. Robinson AJ, Kunji ER. Mitochondrial carrier in the cytoplasmic state have a common substrate binding site.J.Proc Natl Acad Sci U S A, 2006, 103: 2617-2622.
7. Dyall SD,A gius SC, et al..The dynamic dimerization of the yeast ADP/ATP carrier in the inner mitochondrial membrane is affected by conserved cysteine residued. J-Biol-Chem, 2003, 278: 26757-26764.
8. Huang SG, Odoy S and Klimberg M. Chimers of two fused ADP/ATPcarrier monomers indicate a single channel for ADP/ATP transport .Arch-Biochem-Biophys. 2001, 394: 67-75
9. Itoi S, Misaki R, Hirayama M. et al. Identification of three isoforms for mitochondrial adenine nucleotide translocator in the pufferfish Takifugu rubripes. Mitochondrion. 2005, 5(3):162-72.
10. Dolce V, Scarcia P, Iacopetta D, Palmieri F. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Lett, 2005, 579: 633-637.
11. Mikahil Yu VYSSOKIKH,Annette KATZ,Alexander RUECK,Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophillin D. J. Biochem, 2003, 358:349-358
12. Naoshi Yamazaki, Yasuo Shinohara. Structural properties of mammalian mitochondrial ADP/ATPcarriers: identification of possible amino acids that determine functional differences in its isoforms J. Mitochondrion, 2002, 1: 371–379
13. Siekevitz PV,Potter VR. Biochemical structure of mitochondrial intramitochondrial components and oxidative phosphorylation.J. Biol Chem. 1995 ,215: 237-255
14. Pressman BC.Intramitochondrial nueleotides.1.Some factors affecting net interconversion of adenine nucleotides.J Biol Chem.1958,232: 967-978
15. Bruni A.Contessa AR,Lueuni S.Atractyloside as inhibitor of energy-transfer reactions in liver mitochondria.J Biochim Biophys Acta.1962, 60:301-316
16. Kemp A,Slater EC.The site of action of atractyloside.Biochim Biophys Acta. 1964, 92:178-180
17. Vignais PV,Vignais PM,Stanislas EAction of potassium atractyloside on oxidative phosphorylation in mitochondria and submitochondrial particles.J Biochim Biophys Acta. 1962, 60:284-300
18. Chappel JB,Crofts AR.The effect of atractyloside and oligomycin on the behavior of mitochondria towards the adenine nucleotides. J Biochem, 1965, 95:707-716
19. Heldt HW, Jacobs H, Klingenberg M. Endogenous ADP of mitochondria, an early phosphate acceptor of oxydative phosphorylationas disclosed by kinetic studies with
14C-labeled ADP and ATP and with atractyloside. Biochem Biophys Res Common, 1965, 18: 174-179
20. Dalia M.Kopustinskiene,Adenine Nuleotide Translocase Mediates the KATP- Channel- Openers-Induced Proton and Potassium Flux to the Mitochodrial Matrix. Jjournal of Bioenergetics and Biomembranes, 2003, 35: 141-148.
21. Kowaltowski AJ, Seetharaman S, Paucek P, Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria. Am J Physiol Heart Circ Physiol. 2001, 280: 649-657.
22. Krolikowski JG, Bienengraeber M, Weihrauch D. et al. Inhibition of mitochondrialpermeability transition enhances isoflurane-induced cardioprotection during early reperfusion: the role of mitochondrial KATP channels.Anesth Analg. 2005, 101(6): 1590-1596.
23. Lipskaya TY, Savchenko MS. Once again about the functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase. Biochemistry (Mosc), 2003, 68:68-79.
24. Pasdois P, Quinlan CL, Rissa A. et al. Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS.Am J Physiol Heart Circ Physiol, 2007, 292(3):1470-1478.
25. Graham BH, Waymine KG, Cottrell B, Trounce IA, MacGregorGR, Wallace DC. A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heartrmuscle isoform of the adenine nucleotide translocator.Nat Genet, 1997, 16:226–34.
26. Mckenzie M, Liolitsa D, Hanna MG..et al.Mitochondrial disease: mutations and mechanisms. Neurochem Res, 2004, 29(3):589-600.
27. Belen Notario,Csrlos Manchado.Assessment of Membrane-Bound Mammal Mitochondrial Adenine Nucleotide Translocase Topography by Experimental Antibodies. Biochemistry, 2003, 42: 820-828.
28. Christelle Fiore, Delphine Arlot-Guilliga. Fluorometric detection of ADP /ATP carrier deficiency in human muscle J. Clinica Chimica Acta, 2001, 311: 125–135
29. A.Lombardia, E. Silvestrib, M.Skeletal muscle mitochondrial free-fatty-acid content and membrane potential sensitivity in different thyroid states: involvement of uncoupling protein-3 and adenine nucleotide translocase. FEBS Letters, 2002, 532: 12-16
30. Ventura FV, Tavares de Almeida I,Wanders RJ, et al. Inhibition of adenine nucleotide transport in rat liver mitochondria by long-chain acyl-coenzyme A beta-oxidation intermediates. Biochem Biophys Res Commun, 2007, 352: 873-878.
31. Kaukonen J, Zeviani M, Comi GP, Piscaglia MG, Peltonen L, Suomalainen A. A third locus predisposing to multiple deletions of mtDNA in autosomal dominant progressive external ophthalmoplegia. Am J Hum Genet, 1999, 65: 256–61.
32. Kaukonen J, Juselius JK, Tiranti V, et al. Role of adenine nucleotide translocator 1 inmtDNA maintenance. Science, 2000, 289: 782–785.
33. Fiore, C., Trezeguet, V., Le Saux, A., The mitochondrial ADP/ATP carrier: structural, physiological and pathological aspects. Biochimie, 1998, 80: 137–150.
34. Vyssokikh, M.Y., Brdiczka, D., The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis.Acta Biochim. Pol, 2003, 50: 389–404.
35. Crompton,M.,Virji,S.and Ward,J.M. Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine mucleotide translocase to form the permeability transition pore. Eur. J. Biochem, 1998, 258:729-735
36. Susin,S.A, Lorenzo,H.K. Snow,B.E. etal. Molecular characterisation of mitochondrial apoptosis-ducing facter. Nature, 1999, 397: 441-446
37. Garcia N, Maartinez-Abundis E, Pavon N, et al. Copper induces permeability transition through its interaction with the adenine nucleotide translocase. Cell Biol Int, 2007, 25: 1-2
38. Belzacq, A.S., Vieira, H.L., Verrier, F., Bcl-2 and Bax modulate adeninenucleotide translocase activity. Cancer Res, 2003, 63: 541–546.
39. Baucer,M.K.,Rocks,O.and Grimm,S. Adenine nucleotide translocase-1,a component of the permeability transition pore can dominantly induce apoptosis,J.ell Biol, 1999, 147: 1493-1502
40. Mo'nica Zamora, Meritxell Granell. Adenine nucleotide translocase 3 (ANT3) overexpression inducesapoptosis in cultured cells .FEBS Letters, 2004, 563: 155-160
41. Kokoszka JE, Waymire KG, Levy SE,The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature, 2004, 427: 461-465
1. GonzalesGF, GonezC, VillenaAetal. Adreno pause or decline of serum adrenal androgens with age in women living at sea level or at high altitude. J.Endocrinol, 2002, 173(1):95.
2. Vitzthum V J, Ellison PT, Sukalich S, et al. Does hypoxia impair ovarian function in Bolivian women indigenous to high altitude? High Alt Med Biol, 2000, 1(1): 39
3. Escudero F, Gonzales GF, Gonez C. Hormone profile during the menstrual cycle at high altitude. Int J Gynaecol Obstet, 1996, 55(1): 49
4. Sobrevilla LA, Romero I, Kruger F. et al.Low estrogen excretion during pregnancy at high altitude. Am J Obstet Gynecol, 1968, 102(6):828.
5. Zamudio S, Leslie KK,White M. et al. Low serum estradiol and high serum progesterone concentrations characterize hypertensive pregnancies at high altitude. J Soc Gynecol Investig, 1994, 1(3):197.
6. Rhee JW, Longo LD, Pearce WJ. et al. Effect of chronic hypoxia on myometrial responsiveness in the pregnant rat. Am J Physiol, 1996, 270(3): 477
7. Macome JC, Costa LE, Martin IH. et al. Steroid biosythesis by gonads of rat submitted to chronic hypobaric hypoxia. Acta Physiol-Lat-Am, 1977, 27(5): 249.
8. Krebs C, Macara LM, Leiser R, Bowman AW. Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilicl artery is associated with maldevelopment of the placental terminal villous tree.Am J Obstet Gynecol, 1996, 1534-1542.
9. Jansson T, Ekstrand Y, Bjorn C, Wennergren M. Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes, 2002, 51: 2214-2219.
10. McMullen S, Osgerby JC, Thurston LM, Gadd TS. Alterations in placental 11beta-hydroxysteroid dehydrogenase activities and fetal cortisol:cortisone ratios induced by nutritional restriction prior to conception and at defined stages of gestation in ewes. Reproduction 2004, 127: 717-725.
11. Vonnahme KA, Ford SP. Differential expression of the vascular endothelial growth factor-receptor system in the gravid uterus of Yorkshire and Meishan pigs.Bio Reprod, 2004, 71: 163-169.
12. Wallace JM, Aitken RP, Milne JS. Nutritionally mediated placental growth factor-receptor system in the growing adolescent:consequences for the fetus.Biol Reprod 2004, 71: 1055-1062.
13. Jansson T, Ekstrand Y, Bjorn C, Wennergren M.Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes, 2002, 51: 2214-2219.
14. Jansson T, Wennergren M, Powell TL. Placental glucose transport and GLUT1 expression in insulin-dependent diabetes.Am J Obstet Gynecol, 1999, 180: 163- 168.
15. Gansson N, Greenwood SL, Johansson BR, Powell TL. Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments.J Clin Endocrinol Metab 2003, 88:1205-1211.
16. JanssonT, PowellTL. Placental nutrient transfer and fetal growth. Nutrition, 2000, 16: 500-502.
17. Mahendran D, Donnai P, Glazier JD. Amino acid(system A)transporter activity in microvillous membrane vesicles from the placentas of appropriate and small for gestational age babies.Pediatr Res,1993, 34:661-665.
18. Jasson T,Scholtbach V,Powell TL.Placental transport of leucine and lysine is reduced in intrauterine growth restriction.Pediatr Res,1998, 157:2111-2122.
19. Ayuk PT, Theophanous D, D’Souza SW. 1-arginine transport by the microvillous plasma membrane of the syncytiotrophobast from human placenta in relation to nitric oxide production:effects of gestation,preeclampsia,and intrauterine growth restriction.J Clin Endocrinol Metab,2002, 87:747-751.
20. Godfrey KM. Maternal regulation of fetal development and health in adult life.Eur J Obstet Gynecol Reprod Biol,1998, 78:141-150.
21. Nelson DM, Smith SD, Furesz TC. Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts.Am J Physiol Cell Physiol, 2003, 284: 310-315.
22. Cramer S, Beveridge M, Kilberg M. Physiological importance of system A-mediated amino acid transport to rat fetal development.Am J Physiol Cell Physiol, 2002, 282: 153-160.
23. Sibley CP, Coan PM, Ferguson-Smith AC. Placental-specific insulin-like growth factor2IIgf2)regulates the diffusional exchange characteristics of the mouse placenta.Proc Natl Acad Sci USA, 2004, 101: 8204-8208.
24. Lindsay RS, Lindsay RM, Waddell BJ. Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat:studies with the 11 beta-hydroxysteroid dehydrogenase inhibito carbenoxolone. Diabetologia, 1996, 39: 1299-1305.
25. Welberg LA, Seckl JR, Holmes MC. Inhibition of 11beta-hydroxysteroid dehydrogenase the foeto-placental barrier to maternal glucocorticoids,permanently programs amygdale GR mRNA expression and anxiery-like behaviour in the offspring. Eur J Neurosci, 2000, 12: 1047-1054.
26. Krozowski Z, MaGuire JA, Stein-Oakley AN. Immunohistochemical localization of the 11-beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta.J Clin Endocrinol Metab, 1995, 80: 2203-2209.
27. Sechl FR, Cleasby M, Nyirenda MF. Glucocorticoids,11beta- hydroxysteroid dehydrogenase and fetal programming. Kidney Int, 2000, 57: 1412-1417.
28. Murphy VE,Clifton VL.Alterations in human placental 11-beta- hydroxysteroid dehydrogenase type1 and 2 with gestational age and labour. Placenta, 2003, 24: 739-744.
29. Alfaidy N, Gupta S, DeMarco C. Oxygen regulation of placental 11 beta- hydroxysteroid dehydrogenase 2:physiological and pathological implications.J Clin Endocrinol Metab, 2002, 87, 4797-4805.
30. Challis JR, Sloboda DM, Alfaidy N. Prostaglandins and mechanisms of preterm birth. Reproduction 2002, 124:1-17.
31. McMullen S, Osgerby JC, Thurston LM. Alterations in placental 11 beta- hydroxysteroid dehydrogenase (11 betaHSD)activities and fetal cortisol:cortisone ratios induced by nutritional restriction prior to conception and at defined stages of gestation in ewes. Reproduction, 2004, 127: 717-725.
32. Genbacev O, Zhou Y, Ludlow JW. Regulation of human placental development by oxygen tension. Science, 1997, 277: 1669-1672.
33. Burton GJ, Hempstoch J, Jauniaux E. Nutrition of the human fetus during the first trimester-a review. Placenta, 2001, 22: 70-77
34. Jauniaux E, Watson AL, Hempstoch J. Onset of maternal arterial blood flow and placental oxidative stress.A possible factor in human early pregnancy failure.Am J Pathol, 2000, 157: 2111-2122.
35. Padavala S, Pope N, Baker P, et al. An imbalance between vascular endothelial growth factor and its soluble receptor in placental villous explants of intrauterine growth-restricted pregnancies. J Soc Gynecol Investig, 2006, 13: 40-47.
36. Charnock-Jones DS, Kaufmann P, Mayhew TM. Aspects of human fetoplacental vasculogenesis and angiogenesis.I. Molecular regulation. Placenta,2004, 25: 103- 113.
37. Son SM. Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes.Diabetes Res Clin Pract. 2007, 26: 1-2.
38. Atamer Y, Kocyigit Y, Yokus B, et al. Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia.Eur J Obstet Gynecol Reprod Biol, 2005, 119: 60-66.
39. Cui XL, Brockman D, Campos B, Myatt L. Expression of NADPH oxidase isoform 1(Nox1)in human placenta:involvement in preeclampsia. Placenta, 2006, 27: 422-431.
40. Webster RP, Brockman D, Myatt L. et al. Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia. J. Mol Hum Reprod. 2006, 12:677-685.
41. Kossenjans W, Eis A, Aahay R. Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia.Am J Physiol Heart Circ Physiol, 2000, 278: 1311-1319.
42. Mudgett JS, Ding J, Guh-Siesel L, Chartrain NA. Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis.Proc Natl Acad Sci USA, 2000, 97: 10454-10459.
43. Zamudio S, Kovalenko O, Vanderlelie J. et al. Chronic Hypoxia In Vivo ReducesPlacental Oxidative Stress. Placenta. 2007, 7,
44. Zamudio S. High-altitude hypoxia and preeclampsia.Front Biosci. 2007, 12:2967-2977.