不同负荷耐力训练中一氧化氮对大鼠骨骼肌铁代谢的影响
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摘要
中长跑是典型的周期性耐力项目,有氧氧化供能占主导地位。因此氧的摄取和利用效率是影响骨骼肌产生ATP的重要因素。红细胞中的血红蛋白是运氧的重要载体,骨骼肌中肌红蛋白接受并贮存血红蛋白运载的氧,线粒体是有氧代谢的主要场所,电子传递链中的细胞色素水平影响有氧代谢能力。铁参与了血红蛋白、肌红蛋白和细胞色素等物质的合成,因此机体铁状态可以影响氧的转运及线粒体产生ATP的能力,进而影响运动成绩。对于中长跑运动员来说维持机体铁稳态尤其是骨骼肌的铁含量是十分重要的。目前的研究表明我国优秀运动员仍存在运动引起的铁缺乏,以至影响运动能力。关于运动中铁代谢的变化进行了大量研究,但不同负荷的耐力训练对机体尤其是骨骼肌铁代谢的调节机制尚不明确。最新的研究成果表明一氧化氮(NO)可调节巨噬细胞和人白血病细胞的铁代谢。然而目前尚缺乏直接证据证明在运动中NO对骨骼肌细胞铁代谢究竟有何影响,其调节机制还缺乏深入研究。本研究通过在体和离体实验,研究NO对不同负荷耐力训练过程中大鼠骨骼肌铁代谢的调节机制。观察大鼠不同负荷耐力训练后骨骼肌NO含量、骨骼肌铁代谢变化及其相关关系,通过免疫蛋白印迹(Western Blot)观察骨骼肌相关蛋白表达的变化。通过培养大鼠骨骼肌细胞,检测外源NO对肌细胞摄铁和释铁功能、铁转运蛋白表达的影响,阐明运动中NO对骨骼肌铁代谢的调节机制。
研究方法:
在体实验:雄性Wistar大鼠18只,体重300±10g,随机分为对照组、适度运动组和过度运动组,每组6只。对照组大鼠不运动,适度运动组和过度运动组大鼠分别进行不同负荷的递增负荷跑台训练。5周后取材,测定血常规、机体铁状态、组织铁含量及腓肠肌铁代谢相关蛋白表达(TfR1、DMT1(IRE)、DMT1(non-IRE)和FPN1)、血清和腓肠肌一氧化氮合酶(NOS)活性及NO含量。
离体实验:培养L6大鼠成肌细胞,实验组加入0.5mmol/l的NO供体SNAP,对照组用基本培养基,孵育24小时后用同位素铁~(55)Fe测定铁的摄取量与释放量、铁代谢相关蛋白表达(TfR1、DMT1(IRE)、DMT1(non-IRE)和FPN1)。
研究结果:
(1)不同负荷耐力训练对大鼠体重的影响:经过5周不同负荷递增负荷的运动,过度运动组大鼠体重在第3周开始下降,到第5周末体重与对照组相比下降了19.18%(P<0.01),适度运动组体重与对照组无显差别。
(2)不同负荷耐力训练对大鼠血常规的影响:过度运动组大鼠红细胞(RBC)、血红蛋白(Hb)和红细胞压积(Hct)与对照组比较分别下降了32.39%、32.05%和21.30%(P<0.01),而适度运动组大鼠RBC、Hb和Hct均高于对照组和过度运动组(P<0.01)。
(3)不同负荷耐力训练对大鼠机体铁状态的影响:适度运动组和过度运动组大鼠腓肠肌铁含量均显著高于对照组(P<0.01),而适度运动组腓肠肌铁含量显著高于过度运动组(P<0.01)。与对照组相比,适度运动组大鼠血清铁含量和转铁蛋白饱合度增加。过度运动组血清铁含量、转铁蛋白饱合度、血清铁蛋白、骨髓铁含量均比对照组和适度运动组降低。各组血清总铁结合力和肝脏铁含量没有变化。
(4)不同负荷耐力训练对大鼠腓肠肌铁转运蛋白表达的影响:适度运动组和过度运动组大鼠腓肠肌TfR1和DMT1(IRE)蛋白表达量均比对照组高,而两组FPN1蛋白表达量均低于对照组(P<0.05)。适度运动组与过度运动组之间三种蛋白的表达量差异不具有显著性。各组之间DMT1(non-IRE)蛋白表达量均差异不具有显著性。
(5)不同负荷耐力训练对大鼠腓肠肌和血清NO、NOS的影响:过度运动组血清NOS活性和NO含量显著高于对照组和适度运动组(P<0.01),腓肠肌NOS活性和NO含量显著高于对照组(P<0.01)。适度运动组血清NOS活性和NO含量显著高于对照组(P<0.01),腓肠肌NO含量高于对照组(P<0.01),对照组和适度运动组腓肠肌NO含量与腓肠肌铁含量线性相关(r=0.81,P<0.01)。
(6)NO对L6细胞铁代谢的影响:同位素测试结果显示实验组L6细胞铁摄入量比对照组高,铁释放量与对照组比较差异不具有显著性。
(7)NO对L6细胞铁转运相关蛋白表达的影响:实验组L6细胞TfR1、DMT1(IRE)蛋白表达量比对照组高(P<0.05),FPN1蛋白表达量比对照组低(P<0.05),而DMT1(non-IRE)蛋白表达量与对照组比较差异不具有显著性。
结论:
(1)适度运动可通过增加大鼠体内NO,引起腓肠肌细胞膜上向细胞内转运铁的蛋白(TfR1、DMT1(IRE))表达增加,而向细胞外释放铁的FPN1表达降低,导致肌细胞内铁贮量增加。同时增加Hb含量,保证运动中骨骼肌细胞对氧和铁的需求,促进有氧氧化的顺利进行,使机体对运动产生有益的生理适应。
(2)过度运动使大鼠体内NO急剧增加,NO诱发机体贮存铁重新分布,使腓肠肌内铁储量明显增加,但骨髓内铁贮量大幅减少,导致运动性低血色素。同时机体铁储量明显降低。机体大量动员了骨髓中的贮存铁,以保障骨骼肌的铁需求,但并未动员肝脏贮存铁,表明过度运动引发机体铁代谢调控发生紊乱。
(3)一定浓度的NO调节TfR1和DMT1蛋白表达增多,骨骼肌摄铁增加,使骨骼肌内铁贮量增加。
总之,本实验通过在体和离体实验从细胞和分子水平阐明了运动中NO对骨骼肌铁代谢具有一定的调节作用。这种调节作用与运动负荷关系密切。本研究为合理安排训练,防止运动性低血色素发生提供了一定的理论依据和实验基础。
Middle-distance race is a typical periodicity endurance training,and carbohydrate oxidation is the main way to produce energy for exercise.The utilization efficiency of oxygen can affect the production of ATP in skeletal muscle.Hemoglobin(Hb) in the red blood cell can transport oxygen.Myoglobin(Mb) of skeletal muscle can accept and store oxygen transported by Hb.Cytochrome of electron transfer in mitochondrion can affect the ablity of oxidation. Iron is needed for the synthesization of Hb,Mb and Cytochrome.Iron is utilised by the body for oxygen transport and energy production,and therefore iron is essential to athletic performance.Normal iron status in athletes is especially important during exercise.It has been reported that strenuous bouts of prolonged exercise and heavy training were associated with iron deficiency in both animal models and athletes.It is not known whether different load exercise induce iron deficiency.The molecular regulatory mechanism of the changed iron status and iron metabolism in muscle during exercise is not well determined.Some researches reported nitric oxide(NO) may play an important role in iron redistribution in exercise,while the molecular regulatory mechanism of iron metabolism in skeletal muscle was unclear.The present study investigated the effects of NO on iron metabolism in vivo and in vitro in order to illuminate the molecular regulatory mechanism of iron metabolism in exercise.The experiments in vivo:examined the level of iron status,NO,iron storage and the expression of iron transport related proteins in rats' gastrocnemius after 5-week different load treadmill exercise of progressive loading.The experiments in vitro:examined the effects of SNAP(NO donor) on iron release and intake of L6.We hypothesized that NO plays an important role in iron metabolism in gastrocnemius during exercise.
Methods:
The experiments in vivo:18 male Wistar rats(300±10g) were randomly divided into three groups:control group(CG),moderately exercised group(MG) and strenuously exercised group(SG).The status of blood,serum iron,serum ferrtin,NO content and NOS activity,non-haem iron in different tissue were examined after 5-week different load treadmill exercise of progressive loading.The expression of transferrin receptor 1(TfR1)、divalent metal transporter1(DMTl:DMTl(IRE) and DMT1(non-IRE))and ferroportin 1(FPN1) in gastrocnemius of rats were determined by Western Blot.
The experiments in vitro:The L6 cells were treated with SNAP(NO donor)(control group(CG) 0 mM and experimental group(EG) 0.5 mmol/L) for 24 h,and examined the effects of NO on iron release and intake by ~(55)Fe.The expression of TfR1、DMT1(IRE)、DMT1(non-IRE) and FPN1 of L6 cells were determined by Western Blot.
Results:
(1) Effects of different load endurance training on rats' weight:The body weight of SG was significantly decreased 19.18%compared with CG after 5-week training(P<0.01).There was no significantly change between CG and MG.
(2) Effects of different load endurance training on rats' blood status:The red blood cell count,haemoglobin and haematocrit of SG were decread 32.39%、32.05%and 21.30%than that of CG(P<0.01).While the red blood cell(RBC)、Hb and hematocrit(Hct) in MG were increased compared with CG and SG(P<0.01).
(3) Effects of different load endurance training on rats' serum iron status and non-haem iron distribution in different tissues:The non-haem iron in gastrocnemius of SG and MG were significantly increased compared with CG(P<0.01).Serum iron,serum ferritin of MG were increased than that of CG.On the contrary,the serum iron,serum ferritin,TS and non-haem iron in bone marrow of SG were significantly decreased compared with CG and MG.
(4) Effects of different load endurance training on the expression of TfR1、DMT1(IRE)、DMT1(non-IRE) and FPN1 of rats' gastrocnemius:Western Blot showed the expression of TfR1 and DMT1(IRE) were increased in MG and SG than that of CG,while the expression of FPN1 in MG and SG was drcreased comared with CG(P<0.05).There was no significant change of DMT1(non-IRE) among three groups.
(5) Effects of different load endurance training on the level of NO and the activity of NOS in serum and gastrocnemius of rats:The level of NO and the activity of NOS in serum of SG were significantly increased than that of CG and MG(P<0.01).The level of NO and the activity of NOS in gastrocnemius of SG were significantly increased than that of CG(P<0.01). The level of NO and the activity of NOS in serum of MG were significantly increased than that of CG(P<0.01),but lower than that of SG(P<0.01).There is a linearity corelation between the level of NO and iron on rats' gastrocnemius in physiological range(r=0.81,P<0.01).
(6) Effects of NO on iron release and intake of L6 cells:The iron intake was increased of SNAP cells(P<0.01).But there was no significant change of iron release between the two groups.
(7) Effects of NO on the expression of iron transport proteins of L6 cells:The expression of TfR1 and DMT1(IRE) were increased in EG cells than that of CG cells,while the expression of FPN1 was drcreased comared with control cells(P<0.05).But there was no significant change of DMT1(non-IRE) of the expression between the two groups.
Conclusions:
(1)The NO of rats was increased after moderately exercise.The expression of TfR1 and DMT1(IRE) were increased while the expression of FPN1 in gastrocnemius was decreased,in turn the stored iron in gastrocnemius was increased.There was a linearity corelation between the level of NO and iron of rats' gastrocnemius in physiological range.At the same time,the RBC,Hb content,serum iron and transferrin saturation(TS) were also increased than that of CG and MG,which resulted in the elevated O_2 and iron in the skeletal muscle and the increaed oxidation,which was a physioadaptation to exercise.
(2) The NO of rats was rapidly increased after strenuous exercise.Though the non-haem iron of gastrocnemius was increased,the iron in bone marrow was significantly decreased.As a result,the RBC,Hb content,serum iron and TS were significantly decreased,which caused sports hypochrosis.The serum ferritin and the stored iron were decreased.Most of the stored iron in bone marrow was removed to skeletal muscle,while the stored iron was not changed in liver,which showed the iron metabolism was disordered after strenuous exercise.The high load exercise was able to destroy the iron homeostasis.
(3) The increased NO induced by exercise might lead to the changed expression of iron-related proteins in gastrocnemius,which resulted in elevated iron absorption and a reduction of iron release.
Taken together,these data indicated NO played an important role in iron metabolism of skeletal muscle during exercise,and the regulatory process was related to sports load.Our present results provid the experimental base for the arrangement of training,and preventing exercise-induced hypochrosis.
研究方法:
在体实验:雄性Wistar大鼠18只,体重300±10g,随机分为对照组、适度运动组和过度运动组,每组6只。对照组大鼠不运动,适度运动组和过度运动组大鼠分别进行不同负荷的递增负荷跑台训练。5周后取材,测定血常规、机体铁状态、组织铁含量及腓肠肌铁代谢相关蛋白表达(TfR1、DMT1(IRE)、DMT1(non-IRE)和FPN1)、血清和腓肠肌一氧化氮合酶(NOS)活性及NO含量。
离体实验:培养L6大鼠成肌细胞,实验组加入0.5mmol/l的NO供体SNAP,对照组用基本培养基,孵育24小时后用同位素铁~(55)Fe测定铁的摄取量与释放量、铁代谢相关蛋白表达(TfR1、DMT1(IRE)、DMT1(non-IRE)和FPN1)。
研究结果:
(1)不同负荷耐力训练对大鼠体重的影响:经过5周不同负荷递增负荷的运动,过度运动组大鼠体重在第3周开始下降,到第5周末体重与对照组相比下降了19.18%(P<0.01),适度运动组体重与对照组无显差别。
(2)不同负荷耐力训练对大鼠血常规的影响:过度运动组大鼠红细胞(RBC)、血红蛋白(Hb)和红细胞压积(Hct)与对照组比较分别下降了32.39%、32.05%和21.30%(P<0.01),而适度运动组大鼠RBC、Hb和Hct均高于对照组和过度运动组(P<0.01)。
(3)不同负荷耐力训练对大鼠机体铁状态的影响:适度运动组和过度运动组大鼠腓肠肌铁含量均显著高于对照组(P<0.01),而适度运动组腓肠肌铁含量显著高于过度运动组(P<0.01)。与对照组相比,适度运动组大鼠血清铁含量和转铁蛋白饱合度增加。过度运动组血清铁含量、转铁蛋白饱合度、血清铁蛋白、骨髓铁含量均比对照组和适度运动组降低。各组血清总铁结合力和肝脏铁含量没有变化。
(4)不同负荷耐力训练对大鼠腓肠肌铁转运蛋白表达的影响:适度运动组和过度运动组大鼠腓肠肌TfR1和DMT1(IRE)蛋白表达量均比对照组高,而两组FPN1蛋白表达量均低于对照组(P<0.05)。适度运动组与过度运动组之间三种蛋白的表达量差异不具有显著性。各组之间DMT1(non-IRE)蛋白表达量均差异不具有显著性。
(5)不同负荷耐力训练对大鼠腓肠肌和血清NO、NOS的影响:过度运动组血清NOS活性和NO含量显著高于对照组和适度运动组(P<0.01),腓肠肌NOS活性和NO含量显著高于对照组(P<0.01)。适度运动组血清NOS活性和NO含量显著高于对照组(P<0.01),腓肠肌NO含量高于对照组(P<0.01),对照组和适度运动组腓肠肌NO含量与腓肠肌铁含量线性相关(r=0.81,P<0.01)。
(6)NO对L6细胞铁代谢的影响:同位素测试结果显示实验组L6细胞铁摄入量比对照组高,铁释放量与对照组比较差异不具有显著性。
(7)NO对L6细胞铁转运相关蛋白表达的影响:实验组L6细胞TfR1、DMT1(IRE)蛋白表达量比对照组高(P<0.05),FPN1蛋白表达量比对照组低(P<0.05),而DMT1(non-IRE)蛋白表达量与对照组比较差异不具有显著性。
结论:
(1)适度运动可通过增加大鼠体内NO,引起腓肠肌细胞膜上向细胞内转运铁的蛋白(TfR1、DMT1(IRE))表达增加,而向细胞外释放铁的FPN1表达降低,导致肌细胞内铁贮量增加。同时增加Hb含量,保证运动中骨骼肌细胞对氧和铁的需求,促进有氧氧化的顺利进行,使机体对运动产生有益的生理适应。
(2)过度运动使大鼠体内NO急剧增加,NO诱发机体贮存铁重新分布,使腓肠肌内铁储量明显增加,但骨髓内铁贮量大幅减少,导致运动性低血色素。同时机体铁储量明显降低。机体大量动员了骨髓中的贮存铁,以保障骨骼肌的铁需求,但并未动员肝脏贮存铁,表明过度运动引发机体铁代谢调控发生紊乱。
(3)一定浓度的NO调节TfR1和DMT1蛋白表达增多,骨骼肌摄铁增加,使骨骼肌内铁贮量增加。
总之,本实验通过在体和离体实验从细胞和分子水平阐明了运动中NO对骨骼肌铁代谢具有一定的调节作用。这种调节作用与运动负荷关系密切。本研究为合理安排训练,防止运动性低血色素发生提供了一定的理论依据和实验基础。
Middle-distance race is a typical periodicity endurance training,and carbohydrate oxidation is the main way to produce energy for exercise.The utilization efficiency of oxygen can affect the production of ATP in skeletal muscle.Hemoglobin(Hb) in the red blood cell can transport oxygen.Myoglobin(Mb) of skeletal muscle can accept and store oxygen transported by Hb.Cytochrome of electron transfer in mitochondrion can affect the ablity of oxidation. Iron is needed for the synthesization of Hb,Mb and Cytochrome.Iron is utilised by the body for oxygen transport and energy production,and therefore iron is essential to athletic performance.Normal iron status in athletes is especially important during exercise.It has been reported that strenuous bouts of prolonged exercise and heavy training were associated with iron deficiency in both animal models and athletes.It is not known whether different load exercise induce iron deficiency.The molecular regulatory mechanism of the changed iron status and iron metabolism in muscle during exercise is not well determined.Some researches reported nitric oxide(NO) may play an important role in iron redistribution in exercise,while the molecular regulatory mechanism of iron metabolism in skeletal muscle was unclear.The present study investigated the effects of NO on iron metabolism in vivo and in vitro in order to illuminate the molecular regulatory mechanism of iron metabolism in exercise.The experiments in vivo:examined the level of iron status,NO,iron storage and the expression of iron transport related proteins in rats' gastrocnemius after 5-week different load treadmill exercise of progressive loading.The experiments in vitro:examined the effects of SNAP(NO donor) on iron release and intake of L6.We hypothesized that NO plays an important role in iron metabolism in gastrocnemius during exercise.
Methods:
The experiments in vivo:18 male Wistar rats(300±10g) were randomly divided into three groups:control group(CG),moderately exercised group(MG) and strenuously exercised group(SG).The status of blood,serum iron,serum ferrtin,NO content and NOS activity,non-haem iron in different tissue were examined after 5-week different load treadmill exercise of progressive loading.The expression of transferrin receptor 1(TfR1)、divalent metal transporter1(DMTl:DMTl(IRE) and DMT1(non-IRE))and ferroportin 1(FPN1) in gastrocnemius of rats were determined by Western Blot.
The experiments in vitro:The L6 cells were treated with SNAP(NO donor)(control group(CG) 0 mM and experimental group(EG) 0.5 mmol/L) for 24 h,and examined the effects of NO on iron release and intake by ~(55)Fe.The expression of TfR1、DMT1(IRE)、DMT1(non-IRE) and FPN1 of L6 cells were determined by Western Blot.
Results:
(1) Effects of different load endurance training on rats' weight:The body weight of SG was significantly decreased 19.18%compared with CG after 5-week training(P<0.01).There was no significantly change between CG and MG.
(2) Effects of different load endurance training on rats' blood status:The red blood cell count,haemoglobin and haematocrit of SG were decread 32.39%、32.05%and 21.30%than that of CG(P<0.01).While the red blood cell(RBC)、Hb and hematocrit(Hct) in MG were increased compared with CG and SG(P<0.01).
(3) Effects of different load endurance training on rats' serum iron status and non-haem iron distribution in different tissues:The non-haem iron in gastrocnemius of SG and MG were significantly increased compared with CG(P<0.01).Serum iron,serum ferritin of MG were increased than that of CG.On the contrary,the serum iron,serum ferritin,TS and non-haem iron in bone marrow of SG were significantly decreased compared with CG and MG.
(4) Effects of different load endurance training on the expression of TfR1、DMT1(IRE)、DMT1(non-IRE) and FPN1 of rats' gastrocnemius:Western Blot showed the expression of TfR1 and DMT1(IRE) were increased in MG and SG than that of CG,while the expression of FPN1 in MG and SG was drcreased comared with CG(P<0.05).There was no significant change of DMT1(non-IRE) among three groups.
(5) Effects of different load endurance training on the level of NO and the activity of NOS in serum and gastrocnemius of rats:The level of NO and the activity of NOS in serum of SG were significantly increased than that of CG and MG(P<0.01).The level of NO and the activity of NOS in gastrocnemius of SG were significantly increased than that of CG(P<0.01). The level of NO and the activity of NOS in serum of MG were significantly increased than that of CG(P<0.01),but lower than that of SG(P<0.01).There is a linearity corelation between the level of NO and iron on rats' gastrocnemius in physiological range(r=0.81,P<0.01).
(6) Effects of NO on iron release and intake of L6 cells:The iron intake was increased of SNAP cells(P<0.01).But there was no significant change of iron release between the two groups.
(7) Effects of NO on the expression of iron transport proteins of L6 cells:The expression of TfR1 and DMT1(IRE) were increased in EG cells than that of CG cells,while the expression of FPN1 was drcreased comared with control cells(P<0.05).But there was no significant change of DMT1(non-IRE) of the expression between the two groups.
Conclusions:
(1)The NO of rats was increased after moderately exercise.The expression of TfR1 and DMT1(IRE) were increased while the expression of FPN1 in gastrocnemius was decreased,in turn the stored iron in gastrocnemius was increased.There was a linearity corelation between the level of NO and iron of rats' gastrocnemius in physiological range.At the same time,the RBC,Hb content,serum iron and transferrin saturation(TS) were also increased than that of CG and MG,which resulted in the elevated O_2 and iron in the skeletal muscle and the increaed oxidation,which was a physioadaptation to exercise.
(2) The NO of rats was rapidly increased after strenuous exercise.Though the non-haem iron of gastrocnemius was increased,the iron in bone marrow was significantly decreased.As a result,the RBC,Hb content,serum iron and TS were significantly decreased,which caused sports hypochrosis.The serum ferritin and the stored iron were decreased.Most of the stored iron in bone marrow was removed to skeletal muscle,while the stored iron was not changed in liver,which showed the iron metabolism was disordered after strenuous exercise.The high load exercise was able to destroy the iron homeostasis.
(3) The increased NO induced by exercise might lead to the changed expression of iron-related proteins in gastrocnemius,which resulted in elevated iron absorption and a reduction of iron release.
Taken together,these data indicated NO played an important role in iron metabolism of skeletal muscle during exercise,and the regulatory process was related to sports load.Our present results provid the experimental base for the arrangement of training,and preventing exercise-induced hypochrosis.
引文
[1]钱忠明.铁代谢-基础与临床[M].北京:科学出版社,2000.165-277.
[2]常翠青,陈志民,刘晓鹏,et al.中国优秀运动员的营养状况[J].营养学报,2005,27(05):370-373.
[3]Gomme P T,Mccann K B,Bertolini J.Transferrin:structure,function and potential therapeutic actions.[J].Drug Discov Today,2005,10(4):267-273.
[4]Hirose M.The structural mechanism for iron uptake and release by transferrins.[J].Biosci Biotechnol Biochem,2000,64(7):1328-1336.
[5]Ming Q Z,De S X,Lai T P.Changes of transferrin-free iron uptake by bone marrow erythroblasts in strenuously exercised rats.[J].J Nutr Biochem,2000,11(7-8):367-373.
[6]Huebers H A,Finch C A.The physiology of transferrin and transferrin receptors.[J].Physiol Rev,1987,67(2):520-582.
[7]刘玉倩,常彦忠,钱忠明,et al.游泳训练对大鼠腓肠肌铁代谢相关蛋白表达的影响[J].中国运动医学杂志,2005,24(02):147-151.
[8]Gunshin H,Mackenzie B,Berger U V,et al.Cloning and characterization of a mammalian proton-coupled metal-ion transporter.[J].Nature,1997,388(6641):482-488.
[9]Mims M P,Prchal J T.Divalent metal transporter 1.[J].Hematology,2005,10(4):339-345.
[10]Donovan A,Brownlie A,Zhou Y,et al.Positional cloning of zebrafish ferroportinl identifies a conserved vertebrate iron exporter.[J].Nature,2000,403(6771):776-781.
[11]Abboud S,Haile D J.A novel mammalian iron-regulated protein involved in intracellular iron metabolism.[J].J Biol Chem,2000,275(26):19906-19912.
[12]Mckie A T,Marciani P,Rolfs A,et al.A novel duodenal iron-regulated transporter,IREG1,implicated in the basolateral transfer of iron to the circulation.[J].Mol Cell,2000,5(2):299-309.
[13]Mckie A T,Barrow D,Latunde-Dada G O,et al.An iron-regulated ferric reductase associated with the absorption of dietary iron.[J].Science,2001,291(5509):1755-1759.
[14]Theil E C.Ferritin:at the crossroads of iron and oxygen metabolism.[J].J Nutr,2003,133(5 Suppl 1):1549-1553.
[15]Rouault T A.Biochemistry.If the RNA fits,use it.[J].Science,2006,314(5807):1886-1887.
[16]Pantopoulos K.Iron metabolism and the IRE/IRP regulatory system:an update.[J].Ann N Y Acad Sci,2004,1012:1-13.
[17]Galaris D,Pantopoulos K.Oxidative stress and iron homeostasis:mechanistic and health aspects.[J].Crit Rev Clin Lab Sci,2008,45(1):1-23.
[18]Christova T,Templeton D M.Effect of hypoxia on the binding and subcellular distribution of iron regulatory proteins.[J].Mol Cell Biochem,2007,301(1-2):21-32.
[19]Soum E,Drapier J C.Nitric oxide and peroxynitrite promote complete disruption of the[4Fe-4S]cluster of recombinant human iron regulatory protein 1.[J].J Biol Inorg Chem,2003.8(1-2):226-232.
[20]Wallander M L,Zumbrennen K B,Rodansky E S,et al.Iron-independent phosphorylation of iron regulatory protein 2 regulates ferritin during the cell cycle.[J].J Biol Chem,2008,283(35):23589-23598.
[21]Papanikolaou G,Samuels M E,Ludwig E H,et al.Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis.[J].Nat Genet,2004,36(1):77-82.
[22]Rodriguez M A,Niemela O,Parkkila S.Hepatic and extrahepatic expression of the new iron regulatory protein hemojuvelin.[J].Haematologica,2004,89(12):1441-1445.
[23]Rodriguez A,Pan P,Parkkila S.Expression studies of neogenin and its ligand hemojuvelin in mouse tissues.[J].J Histochem Cytochem,2007,55(1):85-96.
[24]Zhang A S,Anderson S A,Meyers K R,et al.Evidence that inhibition of hemojuvelin shedding in response to iron is mediated through neogenin.[J].J Biol Chem,2007,282(17):12547-12556.
[25]Zhang A S.West A P.Wyman A E.et al.Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells.[J].J Biol Chem,2005, 280(40):33885-33894.
[26]Andrews N C.Disorders of iron metabolism.[J].N Engl J Med,1999,341(26):1986-1995.
[27]冯炜权,谢敏豪,王香生,et al.运动生物化学研究进展[M].北京:北京体育大学出版社,2006.191-197.
[28]Qian Z M,Chang Y Z,Leung G,et al.Expression of ferroportin1,hephaestin and ceruloplasmin in rat heart.[J].Biochim Biophys Acta,2007,1772(5):527-532.
[29]刘玉倩,常彦忠,王海涛,et al.运动对大鼠腓肠肌一氧化氮含量和铁转运蛋白表达的影响[J].中国运动医学杂志,2007,26(02):112-115.
[30]Hunter G A,Sampson M P,Ferreira G C.Metal ion substrate inhibition of ferrochelatase.[J].J Biol Chem,2008,283(35):23685-23691.
[31]赵光,肖德生.力竭运动对小鼠骨骼肌6种元素含量的影响[J].体育学刊,2003,10(06):655-656.
[32]刘玉倩,常彦忠,钱忠明,et al.不同强度游泳运动对大鼠不同组织铁分布及血清铁状态的影7响[J].解剖学报,2005,36(05):519-522.
[33]曹建民,田野,赵杰修,et al.运动性低血色素大鼠血清铁及组织铁变化规律的研究[J].北京体育大学学报,2005,28(08):1068-1070.
[34]曹建民,田野,赵杰修,et al.长期运动训练对运动性低血色素大鼠组织转铁蛋白及转铁蛋白受体基因表达的影响[J].北京体育大学学报,2006,29(11):1492-1494.
[35]王冰.北京市西城区妇女和儿童贫血状况及铁营养知识调查[J].中华综合临床医学杂志,2007,9(1):88-90.
[36]Lukaski H C.Vitamin and mineral status:effects on physical performance.[J].Nutrition,2004,20(7-8):632-644.
[37]赵杰修,田野,曹建民,et al.跑台运动和营养补充对大鼠骨骼肌能量代谢酶的影响[J].体育科学,2007,26(01):68-71.
[38]Liew Y F,Shaw N S.Mitochondrial cysteine desulfurase iron-sulfur cluster S and aconitase are post-transcriptionally regulated by dietary iron in skeletal muscle of rats.[J].J Nutr,2005,135(9):2151-2158.
[39]Alessio H M,Hagerman A E,Fulkerson B K,et al.Generation of reactive oxygen species after exhaustive aerobic and isometric exercise.[J].Med Sci Sports Exerc,2000,32(9):1576-1581.
[40]Mochel F,Knight M A,Tong W H,et al.Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance.[J].Am J Hum Genet,2008,82(3):652-660.
[41]Rodriguez A,Hilvo M,Kytomaki L,et al.Effects of iron loading on muscle:genome-wide mRNA expression profiling in the mouse.[J].BMC Genomics,2007,8:379.
[42]Altun M,Edstrom E,Spooner E,et al.Iron load and redox stress in skeletal muscle of aged rats.[J].Muscle Nerve,2007,36(2):223-233.
[43]Jung S H,Deruisseau L R,Kavazis A N,et al.Plantaris muscle of aged rats demonstrates iron accumulation and altered expression of iron regulation proteins.[J].Exp Physiol,2008,93(3):407-414.
[44]Ibrahim W,Chow C K.Dietary vitamin E reduces labile iron in rat tissues.[J].J Biochem Mol Toxicol,2005,19(5):298-303.
[45]Stamler J S,Singel D J,Loscalzo J.Biochemistry of nitric oxide and its redox-activated forms.[J].Science,1992,258(5090):1898-1902.
[46]Palmer R M,Ashton D S,Moncada S.Vascular endothelial cells synthesize nitric oxide from L-arginine.[J].Nature,1988,333(6174):664-666.
[47]Andrew P J,Mayer B.Enzymatic function of nitric oxide synthases.[J].Cardiovasc Res,1999,43(3):521-531.
[48]Harris M B,Mitchell B M,Sood S G,et al.Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise.[J].Eur J Appl Physiol,2008,104(5):795-802.
[49]Mcconell G K,Kingwell B A.Does nitric oxide regulate skeletal muscle glucose uptake during exercise?[J].Exerc Sport Sci Rev,2006,34(1):36-41.
[50]Qian Z M.Nitric oxide and changes of iron metabolism in exercise.[J].Biol Rev Camb Philos Soc,2002,77(4):529-536.
[51]Ho K P.Xiao D S.Ke Y.et al.Exercise decreases cytosolic aconitase activity in the liver,spleen,and bone marrow in rats.[J].Biochem Biophys Res Commun,2001,282(1): 264-267.
[52]Bouton C,Drapier J C.Iron regulatory proteins as NO signal transducers.[J].Sci STKE,2003,2003(182):17.
[53]Kim S,Ponka P.Nitric oxide-mediated modulation of iron regulatory proteins:implication for cellular iron homeostasis.[J].Blood Cells Mol Dis,2002,29(3):400-410.
[54]Watts R N,Richardson D R.Differential effects on cellular iron metabolism of the physiologically relevant diatomic effector molecules,NO and CO,that bind iron.[J].Biochim Biophys Acta,2004,1692(1):1-15.
[55]Paradkar P N,Roth J A.Nitric oxide transcriptionally down-regulates specific isoforms of divalent metal transporter(DMT1) via NF-kappaB.[J].J Neurochem,2006,96(6):1768-1777.
[56]Cheah J H,Kim S F,Hester L D,et al.NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexrasl.[J].Neuron,2006,51(4):431-440.
[57]Watts RN,Richardson D R.Examination of the mechanism of action of nitrogen monoxide on iron uptake from transferrin.[J].J Lab Clin Med,2000,136(2):149-156.
[58]Watts R N,Richardson D R.The mechanism of nitrogen monoxide(NO)-mediated iron mobilization from cells.NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.[J].Eur J Biochem,2002,269(14):3383-3392.
[59]Watts R N,Richardson D R.Nitrogen monoxide(no) and glucose:unexpected links between energy metabolism and no-mediated iron mobilization from cells.[J].J Biol Chem,2001,276(7):4724-4732.
[60]Zaman G J,Versantvoort C H,Smit J J,et al.Analysis of the expression of MRP,the gene for a new putative transmembrane drug transporter,in human multidrug resistant lung cancer cell lines.[J].Cancer Res,1993,53(8):1747-1750.
[61]Lipinski P,Starzynski R R,Drapier J C,et al.Induction of iron regulatory protein 1 RNA-binding activity by nitric oxide is associated with a concomitant increase in the labile iron pool:implications for DNA damage.[J].Biochem Biophys Res Commun,2005,327(1): 349-355.
[62]Chenais B,Morjani H,Drapier J C.Impact of endogenous nitric oxide on microglial cell energy metabolism and labile iron pool.[J].J Neurochem,2002,81(3):615-623.
[63]Kim S,Ponka P.Effects of interferon-gamma and lipopolysaccharide on macrophage iron metabolism are mediated by nitric oxide-induced degradation of iron regulatory protein 2.[J].J Biol Chem,2000,275(9):6220-6226.
[64]Lipton S A,Choi Y B,Pan Z H,et al.A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds.[J].Nature,1993,364(6438):626-632.
[65]Richardson D R,Neumannova V,Ponka P.Nitrogen monoxide decreases iron uptake from transferrin but does not mobilise iron from prelabelled neoplastic cells.[J].Biochim Biophys Acta,1995,1266(3):250-260.
[66]Wardrop S L,Watts R N,Richardson D R.Nitrogen monoxide activates iron regulatory protein 1 RNA-binding activity by two possible mechanisms:effect on the[4Fe-4S]cluster and iron mobilization from cells.[J].Biochemistry,2000,39(10):2748-2758.
[67]Bourdon E,Kang D K,Ghosh M C,et al.The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2.[J].Blood Cells Mol Dis,2003,31(2):247-255.
[68]Wang J,Fillebeen C,Chen G,et al.Sodium nitroprusside promotes IRP2 degradation via an increase in intracellular iron and in the absence of S nitrosylation at C178.[J].Mol Cell Biol,2006,26(5):1948-1954.
[69]Mikhael M,Kim S F,Schranzhofer M,et al.Iron regulatory protein-independent regulation of ferritin synthesis by nitrogen monoxide.[J].FEBS J,2006,273(16):3828-3836.
[70]Richardson D R,Lok H C.The nitric oxide-iron interplay in mammalian cells:transport and storage of dinitrosyl iron complexes.[J].Biochim Biophys Acta,2008,1780(4):638-651.
[71]Robach P,Cairo G,Gelfi C,et al.Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle.[J].Blood,2007,109(11):4724-4731.
[72]林文弢,邱烈峰,翁锡全,et al.低氧暴露对运动性低血红蛋白大鼠血清铁代谢的影响[J].中国运动医学杂志,2007,26(01):66-67.
[73]Bishop G M,Smith M A,Lamanna J C,et al.Iron homeostasis is maintained in the brain,but not the liver,following mild hypoxia.[J].Redox Rep,2007,12(6):257-266.
[74]Fleming R E,Britton R S.Iron Imports.Ⅵ.HFE and regulation of intestinal iron absorption.[J].Am J Physiol Gastrointest Liver Physiol,2006,290(4):590-594.
[75]薛成莲,钱忠明,李琳.铁调素、炎症因子与铁代谢[J].2007,38(2):170-173.
[76]Collins J F,Wessling-Resnick M,Knutson M D.Hepcidin regulation of iron transport.[J].J Nutr,2008,138(11):2284-2288.
[77]Leung P S,Srai S K,Mascarenhas M,et al.Increased duodenal iron uptake and transfer in a rat model of chronic hypoxia is accompanied by reduced hepcidin expression.[J].Gut,2005,54(10):1391-1395.
[78]Hoppe M,Lonnerdal B,Hossain B,et al.Hepcidin,interleukin-6 and hematological iron markers in males before and after heart surgery.[J].J Nutr Biochem,2009,20(1):11-16.
[79]Malyszko J,Mysliwiec M.Hepcidin in anemia and inflammation in chronic kidney disease.[J].Kidney Blood Press Res,2007,30(1):15-30.
[80]Fleming R E.Iron and inflammation:cross-talk between pathways regulating hepcidin.[J].J Mol Med,2008,86(5):491-494.
[81]Yeh K Y,Yeh M,Glass J.Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat.[J].Am J Physiol Gastrointest Liver Physiol,2004,286(3):385-394.
[82]Peeling P,Dawson B,Goodman C,et al.Cumulative effects of consecutive running sessions on hemolysis,inflammation and hepcidin activity.[J].Eur J Appl Physiol,2009.
[83]Ganz T.Molecular control of iron transport.[J].J Am Soc Nephrol,2007,18(2):394-400.
[84]Kong W N,Chang Y Z,Wang S M,et al.Effect of erythropoietin on hepcidin,DMT1with IRE,and hephaestin gene expression in duodenum of rats.[J].J Gastroenterol,2008,43(2):136-143.
[85]Kobayashi Y M,Rader E P,Crawford R W,et al.Sarcolemma-localized nNOS is required to maintain activity after mild exercise.[J].Nature,2008,456(7221):511-515.
[86]Krijt J,Vokurka M,Chang K T,et al.Expression of Rgmc,the murine ortholog of hemojuvelin gene,is modulated by development and inflammation,but not by iron status or erythropoietin.[J].Blood,2004,104(13):4308-4310.
[87]Davies K J,Maguire J J,Brooks G A,et al.Muscle mitochondrial bioenergetics,oxygen supply,and work capacity during dietary iron deficiency and repletion.[J].Am J Physiol,1982,242(6):418-427.
[88]赵中应,冯连世,宗丕芳.运动后恢复过程中大鼠骨骼肌α-肌动蛋白基因的表达[J].中国应用生理学杂志,2000,16(01):56-58.
[89]赵杰修,田野,曹建民,et al.不同运动方式对大鼠血红蛋白浓度的影响——大鼠运动性贫血模型建立方法探讨[J].中国运动医学杂志,2004,23(04):436-440.
[90]廖清奎;罗春华;李强;杨崇礼;李钦伯.缺铁性贫血模型的建立[J].1990,11(8):156-158.
[91]赵杰修,田野,曹建民,et al.运动性贫血机理和防治的研究及探讨[J].中国运动医学杂志,2004,23(02):208-211.
[92]肖德生,车力龙,李月英,et al.长期游泳运动对大鼠铁状态的影响[J].中国应用生理学杂志,2003,19(04):359-362.
[93]Klausner R,Rouault T,Harford J.Regulating the fate of mRNA:the control of cellular iron metabolism.[J].Cell.,1993,72(1):19-28.
[94]Weiss G,Goossen B,Doppler W,et al.Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway.[J].EMBO J,1993,12(9):3651-3657.
[95]Durham W J,Yeckel C W,Miller S L,et al.Exogenous nitric oxide increases basal leg glucose uptake in humans.[J].Metabolism,2003,52(6):662-665.
[96]Levy R M,Prince J M,Billiar T R.Nitric oxide:a clinical primer.[J].Crit Care Med,2005,33(12 Suppl):492-495.
[97]Zhang Y,Davies L R,Martin S M,et al.The nitric oxide donor S-nitroso-N-acetylpenicillamine(SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.[J].Resuscitation.2003.59(3):345-352.
[98]Powers S K,Jackson M J.Exercise-induced oxidative stress:cellular mechanisms and impact on muscle force production.[J].Physiol Rev,2008,88(4):1243-1276.
[99]Xiao D S,Ho K P,Qian Z M.Nitric oxide inhibition decreases bleomycin-detectable iron in spleen,bone marrow cells and heart but not in liver in exercise rats.[J].Mol Cell Biochem,2004,260(1-2):31-37.
[100]Xiao D S,Jiang L,Che L L,et al.Nitric oxide and iron metabolism in exercised rat with L-arginine supplementation.[J].Mol Cell Biochem,2003,252(1-2):65-72.
[101]Huang Y C,Dennis R G,Larkin L,et al.Rapid formation of functional muscle in vitro using fibrin gels.[J].J Appl Physiol,2005,98(2):706-713.
[102]Dupic F,Fruchon S,Bensaid M,et al.Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice.[J].Gut,2002,51(5):648-653.
[103]Nunez M T,Gaete V,Escobar A.Endocytic vesicles contain a calmodulin-activated Ca2+ pump that mediates the inhibition of acidification by calcium.[J].Biochim Biophys Acta,1990,1028(1):21-24.
[104]Nisoli E,Clementi E,Paolucci C,et al.Mitochondrial biogenesis in mammals:the role of endogenous nitric oxide.[J].Science,2003,299(5608):896-899.
[105]Murad F.Shattuck Lecture.Nitric oxide and cyclic GMP in cell signaling and drug development.[J].N Engl J Med,2006,355(19):2003-2011.
[106]Casey J L,Hentze M W,Koeller D M,et al.Iron-responsive elements:regulatory RNA sequences that control mRNA levels and translation.[J].Science,1988,240(4854):924-928.
[107]Gonzalez D,Drapier J C,Bouton C.Endogenous nitration of iron regulatory protein-1(IRl'-l) in nitric oxide-producing murine macrophages:further insight into the mechanism of nitration in vivo and its impact on IRP-1 functions.[J].J Biol Chem,2004,279(41):43345-43351.
[108]Ge X H.Wang Q,Qian Z M,et al.The iron regulatory hormone hepcidin reduces ferioporlin 1 content and iron release in H9C2 cardiomyocytes.[J].J Nutr Biochem,2008.
[109]Liu X B,Hill P.Haile D J.Role of the ferroportin iron-responsive element in iron and nitric oxide dependent gene regulation.[J].Blood Cells Mol Dis,2002,29(3):315-326.
[110]Martini L A,Tchack L,Wood R J.Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells.[J].J Nutr,2002,132(4):693-696.
[111]Gambling L,Danzeisen R,Gair S,et al.Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro.[J].Biochem J,2001,356(Pt 3):883-889.
[112]Chen Y,Qian Z M,Du J,et al.Iron loading inhibits ferroportinl expression in PC12 cells.[J].Neurochem Int,2005,47(7):507-513.
[2]常翠青,陈志民,刘晓鹏,et al.中国优秀运动员的营养状况[J].营养学报,2005,27(05):370-373.
[3]Gomme P T,Mccann K B,Bertolini J.Transferrin:structure,function and potential therapeutic actions.[J].Drug Discov Today,2005,10(4):267-273.
[4]Hirose M.The structural mechanism for iron uptake and release by transferrins.[J].Biosci Biotechnol Biochem,2000,64(7):1328-1336.
[5]Ming Q Z,De S X,Lai T P.Changes of transferrin-free iron uptake by bone marrow erythroblasts in strenuously exercised rats.[J].J Nutr Biochem,2000,11(7-8):367-373.
[6]Huebers H A,Finch C A.The physiology of transferrin and transferrin receptors.[J].Physiol Rev,1987,67(2):520-582.
[7]刘玉倩,常彦忠,钱忠明,et al.游泳训练对大鼠腓肠肌铁代谢相关蛋白表达的影响[J].中国运动医学杂志,2005,24(02):147-151.
[8]Gunshin H,Mackenzie B,Berger U V,et al.Cloning and characterization of a mammalian proton-coupled metal-ion transporter.[J].Nature,1997,388(6641):482-488.
[9]Mims M P,Prchal J T.Divalent metal transporter 1.[J].Hematology,2005,10(4):339-345.
[10]Donovan A,Brownlie A,Zhou Y,et al.Positional cloning of zebrafish ferroportinl identifies a conserved vertebrate iron exporter.[J].Nature,2000,403(6771):776-781.
[11]Abboud S,Haile D J.A novel mammalian iron-regulated protein involved in intracellular iron metabolism.[J].J Biol Chem,2000,275(26):19906-19912.
[12]Mckie A T,Marciani P,Rolfs A,et al.A novel duodenal iron-regulated transporter,IREG1,implicated in the basolateral transfer of iron to the circulation.[J].Mol Cell,2000,5(2):299-309.
[13]Mckie A T,Barrow D,Latunde-Dada G O,et al.An iron-regulated ferric reductase associated with the absorption of dietary iron.[J].Science,2001,291(5509):1755-1759.
[14]Theil E C.Ferritin:at the crossroads of iron and oxygen metabolism.[J].J Nutr,2003,133(5 Suppl 1):1549-1553.
[15]Rouault T A.Biochemistry.If the RNA fits,use it.[J].Science,2006,314(5807):1886-1887.
[16]Pantopoulos K.Iron metabolism and the IRE/IRP regulatory system:an update.[J].Ann N Y Acad Sci,2004,1012:1-13.
[17]Galaris D,Pantopoulos K.Oxidative stress and iron homeostasis:mechanistic and health aspects.[J].Crit Rev Clin Lab Sci,2008,45(1):1-23.
[18]Christova T,Templeton D M.Effect of hypoxia on the binding and subcellular distribution of iron regulatory proteins.[J].Mol Cell Biochem,2007,301(1-2):21-32.
[19]Soum E,Drapier J C.Nitric oxide and peroxynitrite promote complete disruption of the[4Fe-4S]cluster of recombinant human iron regulatory protein 1.[J].J Biol Inorg Chem,2003.8(1-2):226-232.
[20]Wallander M L,Zumbrennen K B,Rodansky E S,et al.Iron-independent phosphorylation of iron regulatory protein 2 regulates ferritin during the cell cycle.[J].J Biol Chem,2008,283(35):23589-23598.
[21]Papanikolaou G,Samuels M E,Ludwig E H,et al.Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis.[J].Nat Genet,2004,36(1):77-82.
[22]Rodriguez M A,Niemela O,Parkkila S.Hepatic and extrahepatic expression of the new iron regulatory protein hemojuvelin.[J].Haematologica,2004,89(12):1441-1445.
[23]Rodriguez A,Pan P,Parkkila S.Expression studies of neogenin and its ligand hemojuvelin in mouse tissues.[J].J Histochem Cytochem,2007,55(1):85-96.
[24]Zhang A S,Anderson S A,Meyers K R,et al.Evidence that inhibition of hemojuvelin shedding in response to iron is mediated through neogenin.[J].J Biol Chem,2007,282(17):12547-12556.
[25]Zhang A S.West A P.Wyman A E.et al.Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells.[J].J Biol Chem,2005, 280(40):33885-33894.
[26]Andrews N C.Disorders of iron metabolism.[J].N Engl J Med,1999,341(26):1986-1995.
[27]冯炜权,谢敏豪,王香生,et al.运动生物化学研究进展[M].北京:北京体育大学出版社,2006.191-197.
[28]Qian Z M,Chang Y Z,Leung G,et al.Expression of ferroportin1,hephaestin and ceruloplasmin in rat heart.[J].Biochim Biophys Acta,2007,1772(5):527-532.
[29]刘玉倩,常彦忠,王海涛,et al.运动对大鼠腓肠肌一氧化氮含量和铁转运蛋白表达的影响[J].中国运动医学杂志,2007,26(02):112-115.
[30]Hunter G A,Sampson M P,Ferreira G C.Metal ion substrate inhibition of ferrochelatase.[J].J Biol Chem,2008,283(35):23685-23691.
[31]赵光,肖德生.力竭运动对小鼠骨骼肌6种元素含量的影响[J].体育学刊,2003,10(06):655-656.
[32]刘玉倩,常彦忠,钱忠明,et al.不同强度游泳运动对大鼠不同组织铁分布及血清铁状态的影7响[J].解剖学报,2005,36(05):519-522.
[33]曹建民,田野,赵杰修,et al.运动性低血色素大鼠血清铁及组织铁变化规律的研究[J].北京体育大学学报,2005,28(08):1068-1070.
[34]曹建民,田野,赵杰修,et al.长期运动训练对运动性低血色素大鼠组织转铁蛋白及转铁蛋白受体基因表达的影响[J].北京体育大学学报,2006,29(11):1492-1494.
[35]王冰.北京市西城区妇女和儿童贫血状况及铁营养知识调查[J].中华综合临床医学杂志,2007,9(1):88-90.
[36]Lukaski H C.Vitamin and mineral status:effects on physical performance.[J].Nutrition,2004,20(7-8):632-644.
[37]赵杰修,田野,曹建民,et al.跑台运动和营养补充对大鼠骨骼肌能量代谢酶的影响[J].体育科学,2007,26(01):68-71.
[38]Liew Y F,Shaw N S.Mitochondrial cysteine desulfurase iron-sulfur cluster S and aconitase are post-transcriptionally regulated by dietary iron in skeletal muscle of rats.[J].J Nutr,2005,135(9):2151-2158.
[39]Alessio H M,Hagerman A E,Fulkerson B K,et al.Generation of reactive oxygen species after exhaustive aerobic and isometric exercise.[J].Med Sci Sports Exerc,2000,32(9):1576-1581.
[40]Mochel F,Knight M A,Tong W H,et al.Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance.[J].Am J Hum Genet,2008,82(3):652-660.
[41]Rodriguez A,Hilvo M,Kytomaki L,et al.Effects of iron loading on muscle:genome-wide mRNA expression profiling in the mouse.[J].BMC Genomics,2007,8:379.
[42]Altun M,Edstrom E,Spooner E,et al.Iron load and redox stress in skeletal muscle of aged rats.[J].Muscle Nerve,2007,36(2):223-233.
[43]Jung S H,Deruisseau L R,Kavazis A N,et al.Plantaris muscle of aged rats demonstrates iron accumulation and altered expression of iron regulation proteins.[J].Exp Physiol,2008,93(3):407-414.
[44]Ibrahim W,Chow C K.Dietary vitamin E reduces labile iron in rat tissues.[J].J Biochem Mol Toxicol,2005,19(5):298-303.
[45]Stamler J S,Singel D J,Loscalzo J.Biochemistry of nitric oxide and its redox-activated forms.[J].Science,1992,258(5090):1898-1902.
[46]Palmer R M,Ashton D S,Moncada S.Vascular endothelial cells synthesize nitric oxide from L-arginine.[J].Nature,1988,333(6174):664-666.
[47]Andrew P J,Mayer B.Enzymatic function of nitric oxide synthases.[J].Cardiovasc Res,1999,43(3):521-531.
[48]Harris M B,Mitchell B M,Sood S G,et al.Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise.[J].Eur J Appl Physiol,2008,104(5):795-802.
[49]Mcconell G K,Kingwell B A.Does nitric oxide regulate skeletal muscle glucose uptake during exercise?[J].Exerc Sport Sci Rev,2006,34(1):36-41.
[50]Qian Z M.Nitric oxide and changes of iron metabolism in exercise.[J].Biol Rev Camb Philos Soc,2002,77(4):529-536.
[51]Ho K P.Xiao D S.Ke Y.et al.Exercise decreases cytosolic aconitase activity in the liver,spleen,and bone marrow in rats.[J].Biochem Biophys Res Commun,2001,282(1): 264-267.
[52]Bouton C,Drapier J C.Iron regulatory proteins as NO signal transducers.[J].Sci STKE,2003,2003(182):17.
[53]Kim S,Ponka P.Nitric oxide-mediated modulation of iron regulatory proteins:implication for cellular iron homeostasis.[J].Blood Cells Mol Dis,2002,29(3):400-410.
[54]Watts R N,Richardson D R.Differential effects on cellular iron metabolism of the physiologically relevant diatomic effector molecules,NO and CO,that bind iron.[J].Biochim Biophys Acta,2004,1692(1):1-15.
[55]Paradkar P N,Roth J A.Nitric oxide transcriptionally down-regulates specific isoforms of divalent metal transporter(DMT1) via NF-kappaB.[J].J Neurochem,2006,96(6):1768-1777.
[56]Cheah J H,Kim S F,Hester L D,et al.NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexrasl.[J].Neuron,2006,51(4):431-440.
[57]Watts RN,Richardson D R.Examination of the mechanism of action of nitrogen monoxide on iron uptake from transferrin.[J].J Lab Clin Med,2000,136(2):149-156.
[58]Watts R N,Richardson D R.The mechanism of nitrogen monoxide(NO)-mediated iron mobilization from cells.NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.[J].Eur J Biochem,2002,269(14):3383-3392.
[59]Watts R N,Richardson D R.Nitrogen monoxide(no) and glucose:unexpected links between energy metabolism and no-mediated iron mobilization from cells.[J].J Biol Chem,2001,276(7):4724-4732.
[60]Zaman G J,Versantvoort C H,Smit J J,et al.Analysis of the expression of MRP,the gene for a new putative transmembrane drug transporter,in human multidrug resistant lung cancer cell lines.[J].Cancer Res,1993,53(8):1747-1750.
[61]Lipinski P,Starzynski R R,Drapier J C,et al.Induction of iron regulatory protein 1 RNA-binding activity by nitric oxide is associated with a concomitant increase in the labile iron pool:implications for DNA damage.[J].Biochem Biophys Res Commun,2005,327(1): 349-355.
[62]Chenais B,Morjani H,Drapier J C.Impact of endogenous nitric oxide on microglial cell energy metabolism and labile iron pool.[J].J Neurochem,2002,81(3):615-623.
[63]Kim S,Ponka P.Effects of interferon-gamma and lipopolysaccharide on macrophage iron metabolism are mediated by nitric oxide-induced degradation of iron regulatory protein 2.[J].J Biol Chem,2000,275(9):6220-6226.
[64]Lipton S A,Choi Y B,Pan Z H,et al.A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds.[J].Nature,1993,364(6438):626-632.
[65]Richardson D R,Neumannova V,Ponka P.Nitrogen monoxide decreases iron uptake from transferrin but does not mobilise iron from prelabelled neoplastic cells.[J].Biochim Biophys Acta,1995,1266(3):250-260.
[66]Wardrop S L,Watts R N,Richardson D R.Nitrogen monoxide activates iron regulatory protein 1 RNA-binding activity by two possible mechanisms:effect on the[4Fe-4S]cluster and iron mobilization from cells.[J].Biochemistry,2000,39(10):2748-2758.
[67]Bourdon E,Kang D K,Ghosh M C,et al.The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2.[J].Blood Cells Mol Dis,2003,31(2):247-255.
[68]Wang J,Fillebeen C,Chen G,et al.Sodium nitroprusside promotes IRP2 degradation via an increase in intracellular iron and in the absence of S nitrosylation at C178.[J].Mol Cell Biol,2006,26(5):1948-1954.
[69]Mikhael M,Kim S F,Schranzhofer M,et al.Iron regulatory protein-independent regulation of ferritin synthesis by nitrogen monoxide.[J].FEBS J,2006,273(16):3828-3836.
[70]Richardson D R,Lok H C.The nitric oxide-iron interplay in mammalian cells:transport and storage of dinitrosyl iron complexes.[J].Biochim Biophys Acta,2008,1780(4):638-651.
[71]Robach P,Cairo G,Gelfi C,et al.Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle.[J].Blood,2007,109(11):4724-4731.
[72]林文弢,邱烈峰,翁锡全,et al.低氧暴露对运动性低血红蛋白大鼠血清铁代谢的影响[J].中国运动医学杂志,2007,26(01):66-67.
[73]Bishop G M,Smith M A,Lamanna J C,et al.Iron homeostasis is maintained in the brain,but not the liver,following mild hypoxia.[J].Redox Rep,2007,12(6):257-266.
[74]Fleming R E,Britton R S.Iron Imports.Ⅵ.HFE and regulation of intestinal iron absorption.[J].Am J Physiol Gastrointest Liver Physiol,2006,290(4):590-594.
[75]薛成莲,钱忠明,李琳.铁调素、炎症因子与铁代谢[J].2007,38(2):170-173.
[76]Collins J F,Wessling-Resnick M,Knutson M D.Hepcidin regulation of iron transport.[J].J Nutr,2008,138(11):2284-2288.
[77]Leung P S,Srai S K,Mascarenhas M,et al.Increased duodenal iron uptake and transfer in a rat model of chronic hypoxia is accompanied by reduced hepcidin expression.[J].Gut,2005,54(10):1391-1395.
[78]Hoppe M,Lonnerdal B,Hossain B,et al.Hepcidin,interleukin-6 and hematological iron markers in males before and after heart surgery.[J].J Nutr Biochem,2009,20(1):11-16.
[79]Malyszko J,Mysliwiec M.Hepcidin in anemia and inflammation in chronic kidney disease.[J].Kidney Blood Press Res,2007,30(1):15-30.
[80]Fleming R E.Iron and inflammation:cross-talk between pathways regulating hepcidin.[J].J Mol Med,2008,86(5):491-494.
[81]Yeh K Y,Yeh M,Glass J.Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat.[J].Am J Physiol Gastrointest Liver Physiol,2004,286(3):385-394.
[82]Peeling P,Dawson B,Goodman C,et al.Cumulative effects of consecutive running sessions on hemolysis,inflammation and hepcidin activity.[J].Eur J Appl Physiol,2009.
[83]Ganz T.Molecular control of iron transport.[J].J Am Soc Nephrol,2007,18(2):394-400.
[84]Kong W N,Chang Y Z,Wang S M,et al.Effect of erythropoietin on hepcidin,DMT1with IRE,and hephaestin gene expression in duodenum of rats.[J].J Gastroenterol,2008,43(2):136-143.
[85]Kobayashi Y M,Rader E P,Crawford R W,et al.Sarcolemma-localized nNOS is required to maintain activity after mild exercise.[J].Nature,2008,456(7221):511-515.
[86]Krijt J,Vokurka M,Chang K T,et al.Expression of Rgmc,the murine ortholog of hemojuvelin gene,is modulated by development and inflammation,but not by iron status or erythropoietin.[J].Blood,2004,104(13):4308-4310.
[87]Davies K J,Maguire J J,Brooks G A,et al.Muscle mitochondrial bioenergetics,oxygen supply,and work capacity during dietary iron deficiency and repletion.[J].Am J Physiol,1982,242(6):418-427.
[88]赵中应,冯连世,宗丕芳.运动后恢复过程中大鼠骨骼肌α-肌动蛋白基因的表达[J].中国应用生理学杂志,2000,16(01):56-58.
[89]赵杰修,田野,曹建民,et al.不同运动方式对大鼠血红蛋白浓度的影响——大鼠运动性贫血模型建立方法探讨[J].中国运动医学杂志,2004,23(04):436-440.
[90]廖清奎;罗春华;李强;杨崇礼;李钦伯.缺铁性贫血模型的建立[J].1990,11(8):156-158.
[91]赵杰修,田野,曹建民,et al.运动性贫血机理和防治的研究及探讨[J].中国运动医学杂志,2004,23(02):208-211.
[92]肖德生,车力龙,李月英,et al.长期游泳运动对大鼠铁状态的影响[J].中国应用生理学杂志,2003,19(04):359-362.
[93]Klausner R,Rouault T,Harford J.Regulating the fate of mRNA:the control of cellular iron metabolism.[J].Cell.,1993,72(1):19-28.
[94]Weiss G,Goossen B,Doppler W,et al.Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway.[J].EMBO J,1993,12(9):3651-3657.
[95]Durham W J,Yeckel C W,Miller S L,et al.Exogenous nitric oxide increases basal leg glucose uptake in humans.[J].Metabolism,2003,52(6):662-665.
[96]Levy R M,Prince J M,Billiar T R.Nitric oxide:a clinical primer.[J].Crit Care Med,2005,33(12 Suppl):492-495.
[97]Zhang Y,Davies L R,Martin S M,et al.The nitric oxide donor S-nitroso-N-acetylpenicillamine(SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.[J].Resuscitation.2003.59(3):345-352.
[98]Powers S K,Jackson M J.Exercise-induced oxidative stress:cellular mechanisms and impact on muscle force production.[J].Physiol Rev,2008,88(4):1243-1276.
[99]Xiao D S,Ho K P,Qian Z M.Nitric oxide inhibition decreases bleomycin-detectable iron in spleen,bone marrow cells and heart but not in liver in exercise rats.[J].Mol Cell Biochem,2004,260(1-2):31-37.
[100]Xiao D S,Jiang L,Che L L,et al.Nitric oxide and iron metabolism in exercised rat with L-arginine supplementation.[J].Mol Cell Biochem,2003,252(1-2):65-72.
[101]Huang Y C,Dennis R G,Larkin L,et al.Rapid formation of functional muscle in vitro using fibrin gels.[J].J Appl Physiol,2005,98(2):706-713.
[102]Dupic F,Fruchon S,Bensaid M,et al.Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice.[J].Gut,2002,51(5):648-653.
[103]Nunez M T,Gaete V,Escobar A.Endocytic vesicles contain a calmodulin-activated Ca2+ pump that mediates the inhibition of acidification by calcium.[J].Biochim Biophys Acta,1990,1028(1):21-24.
[104]Nisoli E,Clementi E,Paolucci C,et al.Mitochondrial biogenesis in mammals:the role of endogenous nitric oxide.[J].Science,2003,299(5608):896-899.
[105]Murad F.Shattuck Lecture.Nitric oxide and cyclic GMP in cell signaling and drug development.[J].N Engl J Med,2006,355(19):2003-2011.
[106]Casey J L,Hentze M W,Koeller D M,et al.Iron-responsive elements:regulatory RNA sequences that control mRNA levels and translation.[J].Science,1988,240(4854):924-928.
[107]Gonzalez D,Drapier J C,Bouton C.Endogenous nitration of iron regulatory protein-1(IRl'-l) in nitric oxide-producing murine macrophages:further insight into the mechanism of nitration in vivo and its impact on IRP-1 functions.[J].J Biol Chem,2004,279(41):43345-43351.
[108]Ge X H.Wang Q,Qian Z M,et al.The iron regulatory hormone hepcidin reduces ferioporlin 1 content and iron release in H9C2 cardiomyocytes.[J].J Nutr Biochem,2008.
[109]Liu X B,Hill P.Haile D J.Role of the ferroportin iron-responsive element in iron and nitric oxide dependent gene regulation.[J].Blood Cells Mol Dis,2002,29(3):315-326.
[110]Martini L A,Tchack L,Wood R J.Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells.[J].J Nutr,2002,132(4):693-696.
[111]Gambling L,Danzeisen R,Gair S,et al.Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro.[J].Biochem J,2001,356(Pt 3):883-889.
[112]Chen Y,Qian Z M,Du J,et al.Iron loading inhibits ferroportinl expression in PC12 cells.[J].Neurochem Int,2005,47(7):507-513.
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