辐射诱导人淋巴细胞线粒体基因表达改变的研究
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摘要
背景与目的:
研究发现辐射可以诱导mtDNA突变和mtDNA拷贝数的变化,而突变的mtDNA和mtDNA拷贝数的改变都可进一步导致线粒体基因表达的改变,进而影响细胞的正常功能。然而目前有关辐射诱导线粒体基因表达的研究较少,且研究结果十分不一致。为此,本研究以人淋巴细胞株为研究对象,探索~(60)Coγ射线照射后线粒体基因表达改变的量效关系和时效关系,同时观察照射后呼吸链酶复合体Ⅳ(COX)活性的改变,以期摸索出辐射敏感的线粒体基因及其表达的时效、量效关系,为后期探索放射生物学领域中快速剂量估算这一难题提供基础理论依据。
方法:
1.以剂量率为1Gy/min的~(60)Coγ射线进行人淋巴细胞株的照射,分析量效关系时,剂量分别为1、3、5、8和10Gy,照射后培养8h;分析时效关系时剂量为5Gy,照射后分别培养0.5、4、8、12、24、48和72h。
2.探索转录水平上辐射对淋巴细胞线粒体基因表达的影响时,首先利用逆转录PCR方法分别摸索13种线粒体基因的最佳PCR实验条件,然后利用Real-time PCR方法定量检测线粒体基因表达水平。
3.探索翻译水平上辐射对淋巴细胞线粒体基因表达的影响时,利用流式细胞仪检测线粒体COXⅠ、COXⅡ和COXⅢ蛋白表达水平。
4.线粒体COX活性的检测是通过分光光度计测定550nm处COX吸收峰值的改变来反映COX活性的变化。
结果:
1.~(60)Coγ射线照射人淋巴细胞后,线粒体基因在转录水平上的表达改变:量效关系方面,1～10Gy剂量照射后淋巴细胞线粒体基因表达普遍上调,大部分基因在3或8Gy剂量照射后表达增强较明显,COXⅠ、COXⅢ和ND3基因在3Gy剂量范围内呈现明显的量效关系。COXⅡ、ND2、ND5、Cytb和ATPase8基因在8Gy剂量范围内呈现明显的量效关系;时效关系方面,5Gy剂量照射后,除COXⅠ基因表达下调外,其余基因表达总体上调,照射后4h左右表达增强最显著,24h左右表达上调也十分明显,且大部分基因可持续高表达至48或72h。
2.~(60)Coγ射线照射人淋巴细胞后,线粒体COX的三个亚基在翻译水平上的表达改变:当辐射剂量达到3.5Gy时,COXⅠ和Ⅱ蛋白表达明显增强;当5Gy剂量照射后4-8h,COXⅠ和Ⅱ蛋白表达才明显上调,而COXⅢ蛋白表达普遍下调。
3.~(60)Coγ射线照射剂量达到3Gy时,才出现COX活性显著减弱,5Gy剂量照射0.5h后COX活性持续减弱。
结论:
1.辐射可以诱导人淋巴细胞线粒体基因表达的改变。
2.在转录水平上,辐射可以诱导人淋巴细胞13种线粒体基因表达总体上调,其中COXⅢ和ND3基因在3Gy剂量范围内呈现十分良好的量效关系。照射后4h左右线粒体基因表达增强最显著,24h左右表达上调也十分明显,且大部分基因可持续高表达至48或72h。
3.在翻译水平上,辐射可以诱导人淋巴细胞线粒体COXⅠ和COXⅡ蛋白表达总体上调,COXⅢ蛋白表达显著下调。
4.辐射可以诱导人淋巴细胞线粒体COX活性持续降低。
Background and Objective:
A number of studies indicated that irradiation can induce mtDNA mutation and changes in mtDNA copy number,which can contribute to the changes of mitochondrial genes expression.However,the relationship between irradiation and mitochondrial genes expression has rarely been studied,and the results of investigations are varied.For these reasons,we explore the alterations in expression level of human lymphoblastoid cell mitochondrial genes and the activities of respiratory chain complexesⅣinduced by ~(60)Coγ-rays.
Methods:
1.Human lymphoblastoid cell lines were irradiated with ~(60)Coγ-rays at dose rate of 1Gy/min.The cells were cultured 8h after irradiation of 1～10Gy absorbed dose in order to detect the dose-effect relationship between the dose and expression changes of 13 mitochondrial genes,which encoded peptides.While the expression changes of these genes were analyzed at different post-irradiation time-points between 0.5 and 72h after irradiation of 5Gy in order to explore the time-effect relationship.
2.Changes in mitochondrial genes mRNA level were detected by Real-time PCR after the PCR parameters were qualified by RT-PCR.
3.Changes in mitochondrial genes COXⅠ,COXⅡand COXⅢprotein expression level were determined by flow cytometry(FCM).
4.Spectrophotometric analysis was applied to detect the COX activities.
Results:
1.The expression level of 13 mitonchondrial genes mRNAs in human lymphocytes were generally up-regulated after 1～10Gy irradiation,and the expression peak of most genes were at 3 or 8Gy exposure.The expression changes of COXⅠ, COXⅢand ND3 genes showed the dose-effect relationship after 1-3 Gy ~(60)Coγ-rays exposure;COXⅡ,ND2,ND5,Cyt b and ATPase8 gene expression changes showed the dose-effect relationship after 1-8 Gy exposure.Meanwhile the expression levels of mitochondrial genes mRNAs were elevated most significantly by 4h after 5Gy radiation except COXⅠ.
2.Expression changes of COXⅠand COXⅡprotein were increased significantly after 3-5Gy exposure,while alterations in COXⅠand COXⅡprotein expression were elevated significantly 4-8h after 5Gy irradiation.In addition,COXⅢprotein expression levels were down-regulated generally.
3.Activity of COX was found to be decreased significantly after exposure to 3-10Gy.It decreased significantly at 4-72h after exposure to 5Gy irradiation.
Conclusions:
1.Ionizing radiation might induce significant changes in mitochondrial gene expression.
2.The expression levels of human lymphoblastoid cell mitochondrial genes mRNAs are generally up-regulated following ~(60)Coγ-rays irradiation and the expression changes of COXⅢand ND3 genes show the excellent dose-effect relationship after 1-3 Gy ~(60)Coγ-rays exposure.The expression peak changes of the 13 mitochondrial genes are at 4 h after irradiation.
3.The expression levels of COXⅠand COXⅡprotein are increased comprehensively,while COXⅢprotein expression level is decreased generally after ~(60)Coγ-rays exposure.
4.Activity of COX was decreased generally after ~(60)Coγ-rays exposure.
研究发现辐射可以诱导mtDNA突变和mtDNA拷贝数的变化,而突变的mtDNA和mtDNA拷贝数的改变都可进一步导致线粒体基因表达的改变,进而影响细胞的正常功能。然而目前有关辐射诱导线粒体基因表达的研究较少,且研究结果十分不一致。为此,本研究以人淋巴细胞株为研究对象,探索~(60)Coγ射线照射后线粒体基因表达改变的量效关系和时效关系,同时观察照射后呼吸链酶复合体Ⅳ(COX)活性的改变,以期摸索出辐射敏感的线粒体基因及其表达的时效、量效关系,为后期探索放射生物学领域中快速剂量估算这一难题提供基础理论依据。
方法:
1.以剂量率为1Gy/min的~(60)Coγ射线进行人淋巴细胞株的照射,分析量效关系时,剂量分别为1、3、5、8和10Gy,照射后培养8h;分析时效关系时剂量为5Gy,照射后分别培养0.5、4、8、12、24、48和72h。
2.探索转录水平上辐射对淋巴细胞线粒体基因表达的影响时,首先利用逆转录PCR方法分别摸索13种线粒体基因的最佳PCR实验条件,然后利用Real-time PCR方法定量检测线粒体基因表达水平。
3.探索翻译水平上辐射对淋巴细胞线粒体基因表达的影响时,利用流式细胞仪检测线粒体COXⅠ、COXⅡ和COXⅢ蛋白表达水平。
4.线粒体COX活性的检测是通过分光光度计测定550nm处COX吸收峰值的改变来反映COX活性的变化。
结果:
1.~(60)Coγ射线照射人淋巴细胞后,线粒体基因在转录水平上的表达改变:量效关系方面,1～10Gy剂量照射后淋巴细胞线粒体基因表达普遍上调,大部分基因在3或8Gy剂量照射后表达增强较明显,COXⅠ、COXⅢ和ND3基因在3Gy剂量范围内呈现明显的量效关系。COXⅡ、ND2、ND5、Cytb和ATPase8基因在8Gy剂量范围内呈现明显的量效关系;时效关系方面,5Gy剂量照射后,除COXⅠ基因表达下调外,其余基因表达总体上调,照射后4h左右表达增强最显著,24h左右表达上调也十分明显,且大部分基因可持续高表达至48或72h。
2.~(60)Coγ射线照射人淋巴细胞后,线粒体COX的三个亚基在翻译水平上的表达改变:当辐射剂量达到3.5Gy时,COXⅠ和Ⅱ蛋白表达明显增强;当5Gy剂量照射后4-8h,COXⅠ和Ⅱ蛋白表达才明显上调,而COXⅢ蛋白表达普遍下调。
3.~(60)Coγ射线照射剂量达到3Gy时,才出现COX活性显著减弱,5Gy剂量照射0.5h后COX活性持续减弱。
结论:
1.辐射可以诱导人淋巴细胞线粒体基因表达的改变。
2.在转录水平上,辐射可以诱导人淋巴细胞13种线粒体基因表达总体上调,其中COXⅢ和ND3基因在3Gy剂量范围内呈现十分良好的量效关系。照射后4h左右线粒体基因表达增强最显著,24h左右表达上调也十分明显,且大部分基因可持续高表达至48或72h。
3.在翻译水平上,辐射可以诱导人淋巴细胞线粒体COXⅠ和COXⅡ蛋白表达总体上调,COXⅢ蛋白表达显著下调。
4.辐射可以诱导人淋巴细胞线粒体COX活性持续降低。
Background and Objective:
A number of studies indicated that irradiation can induce mtDNA mutation and changes in mtDNA copy number,which can contribute to the changes of mitochondrial genes expression.However,the relationship between irradiation and mitochondrial genes expression has rarely been studied,and the results of investigations are varied.For these reasons,we explore the alterations in expression level of human lymphoblastoid cell mitochondrial genes and the activities of respiratory chain complexesⅣinduced by ~(60)Coγ-rays.
Methods:
1.Human lymphoblastoid cell lines were irradiated with ~(60)Coγ-rays at dose rate of 1Gy/min.The cells were cultured 8h after irradiation of 1～10Gy absorbed dose in order to detect the dose-effect relationship between the dose and expression changes of 13 mitochondrial genes,which encoded peptides.While the expression changes of these genes were analyzed at different post-irradiation time-points between 0.5 and 72h after irradiation of 5Gy in order to explore the time-effect relationship.
2.Changes in mitochondrial genes mRNA level were detected by Real-time PCR after the PCR parameters were qualified by RT-PCR.
3.Changes in mitochondrial genes COXⅠ,COXⅡand COXⅢprotein expression level were determined by flow cytometry(FCM).
4.Spectrophotometric analysis was applied to detect the COX activities.
Results:
1.The expression level of 13 mitonchondrial genes mRNAs in human lymphocytes were generally up-regulated after 1～10Gy irradiation,and the expression peak of most genes were at 3 or 8Gy exposure.The expression changes of COXⅠ, COXⅢand ND3 genes showed the dose-effect relationship after 1-3 Gy ~(60)Coγ-rays exposure;COXⅡ,ND2,ND5,Cyt b and ATPase8 gene expression changes showed the dose-effect relationship after 1-8 Gy exposure.Meanwhile the expression levels of mitochondrial genes mRNAs were elevated most significantly by 4h after 5Gy radiation except COXⅠ.
2.Expression changes of COXⅠand COXⅡprotein were increased significantly after 3-5Gy exposure,while alterations in COXⅠand COXⅡprotein expression were elevated significantly 4-8h after 5Gy irradiation.In addition,COXⅢprotein expression levels were down-regulated generally.
3.Activity of COX was found to be decreased significantly after exposure to 3-10Gy.It decreased significantly at 4-72h after exposure to 5Gy irradiation.
Conclusions:
1.Ionizing radiation might induce significant changes in mitochondrial gene expression.
2.The expression levels of human lymphoblastoid cell mitochondrial genes mRNAs are generally up-regulated following ~(60)Coγ-rays irradiation and the expression changes of COXⅢand ND3 genes show the excellent dose-effect relationship after 1-3 Gy ~(60)Coγ-rays exposure.The expression peak changes of the 13 mitochondrial genes are at 4 h after irradiation.
3.The expression levels of COXⅠand COXⅡprotein are increased comprehensively,while COXⅢprotein expression level is decreased generally after ~(60)Coγ-rays exposure.
4.Activity of COX was decreased generally after ~(60)Coγ-rays exposure.
引文
[1] Silva LA, Pinho CA, Scarabelot KS, et al. Physical exercise increases mitochondrial function and reduces oxidative damage in skeletal muscle. Eur J Appl Physiol, 2009,105(6):861-867.
[2] Ricci C, Pastukh V, Leonard J, et al. Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am J Physiol Cell Physiol, 2008, 294(2):C413-422.
[3] Khrapko K, Vijg J. Mitochondrial DNA mutations and aging: devils in the details? Trends Genet, 2009, 25(2):91-98.
[4] Camins A, Pallas M, Silvestre JS. Apoptotic mechanisms involved in neurodegenerative diseases: experimental and therapeutic approaches. Methods Find Exp Clin Pharmacol, 2008, 30(1):43-65.
[5] Urba(?)ska EM. Seizures evoked by mitochondrial toxin, 3-nitropropionic acid: new mechanism of epileptogenesis? Pol J Pharmacol, 2000, 52(1):55-57.
[6] Sompol P, Ittarat W, Tangpong J, et al. A neuronal model of Alzheimer's disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Neuroscience, 2008, 153(1):120-130.
[7] Parrella P, Xiao Y, Fliss M, et al. Detection of mitochondrial DNA mutations in primary breast cancer and fine - needle aspirates. Cancer Res, 2001, 61(20):7623-7626.
[8] Kumimoto H, Yamane Y, Nishimoto Y, et al. Frequent somatic mutations of mitochondrial DNAin esoghageal squamous cell carcinoma. Int J Cancer, 2004, 108(2): 228-231.
[9] Tong BC, Ha PK, Dhir K, et al. Mitochondrial DNA alterations in thyroid cancer. J Surg Oncol, 2003, 82(3): 170-173.
[10] Zhao YB, Yang HY, Zhang XW, et al. Mutation in D-loop region of mitochondrial DNA in gastric cancer and its significance. World J Gastroenterol, 2005, 11(21):3304-3306.
[11] Dmitrenko V, Shostak K, Boyko O, et al. Reduction of the transcription level of the mitochondrial genome in human glioblastoma. Cancer Lett, 2005,218(1): 99-107.
[12] Clarke SJ, Khaliulin I, Das M, et al. Inhibition of mitochondrial permeability transition pore opening by ischemic preconditioning is probably mediated by reduction of oxidative stress rather than mitochondrial protein phosphorylation. Circ Res, 2008, 102(9): 1082-1090.
[13] Akopova OV. The role of mitochondrial permeability transition pore in transmembrane Ca~(2+)-exchange in mitochondria. Ukr Biokhim Zh, 2008, 80(3):40-47.
[14] Wang ZB, Liu YQ, Zhang Y, et al. Reactive oxygen species, but not mitochondrial membrane potential, is associated with radiation-induced apoptosis of AHH-1 human lymphoblastoid cells. Cell Biol Int, 2007, 31(11):1353-1358.
[15] Knudson CM, Brown NM. Mitochondria potential, bax "activation," and programmed cell death. Methods Mol Biol, 2008,414: 95-108.
[16] Kose K, Hiyama T, Tanaka S, et al. Nuclear and mitochondrial DNA microsatellite instability in gastrointestinal stromal tumors. Pathobiology, 2006, 73(2):93-97.
[17] Meissner C, Bruse P, Mohamed SA, The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more? Exp Gerontol, 2008, 43(7):645-652.
[18] Behar DM, Blue-Smith J, Soria-Hernanz DF, et al. A novel 154-bp deletion in the human mitochondrial DNA control region in healthy individuals. Hum Mutat, 2008, 29(12):1387-1391.
[19] Malakhova L, Bezlepkin VG, Antipova V, et al. The increase in mitochondrial DNA copy number in the tissues of gamma-irradiated mice. Cell Mol Biol Lett, 2005, 10(4):721-732.
[20] R(o|¨)tig A, Munnich A. Genetic features of mitochondrial respiratory chain disorders. J Am Soc Nephrol, 2003, 14(12):2995-3007.
[21] Wallace DC. Mitochondrial disease in man and mouse. Science, 1999, 283 (5407):1482-1488.
[22]Ta kaoY agi,B youngBooSeo,SalvatoreDiBemardo,et al.NADH Dehydrogenases:From Basic Science to Biomedicine.Journal of B ioenergeticsa ndB iomembranes.2001,33(33):233-24.
[23]柏干荣,陆松敏.线粒体DNA编码细胞色素氧化酶亚基基因的进展.国外医学分子生物学分册,2003,25(6):354-357.
[24]Vijayasarathy C,Damle S,Prabu SK,et al.Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia.Eur J Biochem,2003,270(5):871-879.
[25]Shokolenko I,Venediktova N,Bochkareva A,et al.Oxidative stress induces degradation ofmitochondrial DNA.Nucleic Acids Res,2009,37(8):2539-2548.
[26]Wang L,Kuwahara Y,Li L,Baba T,Analysis of Common Deletion(CD)and a novel deletion of mitochondrial DNA induced by ionizing radiation.Int J Radiat Biol,2007,83(7):433-442.
[27]柳君泽,高文祥,蔡明春,等.ATP浓度和缺氧暴露对大鼠脑线粒体RNA和蛋白质体外合成的影响[J].生理学报,2002,54(6):485-489.
[28]Chu J,Tong M,de la Monte SM.Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons.Acta Neuropathol(Berl),2007,113(6):659-673.
[29]谢燕,江海洪,龚茜芬,等.微波辐照对大鼠脑海马和皮层神经细胞线粒体超微结构及mtTFA mRNA表达的影响.中华劳动卫生职业病杂志,2004,22(2):104-107.
[30]孙玉兰,胡义德,钱海洪.X射线诱导人肺腺癌A549细胞凋亡及线粒体DNA 基因表达下调.中华放射医学与防护杂志,2007,27(5):433-437.
[31]B.Gong,Q.Chen,A.Almasan.Ionizing radiation stimulates mitochondrial gene expression and activity.Radiat Res,1998,150:505-512.
[32]Roychoudhury P,Ghosh U,Bhattacharyya NP,et al.Activation of mitochondrial promoter P_(H)-binding protein in a radio-resistant Chinese hamster cell strain associated with Bcl-2.Biochem Biophys Res Commun,2006,350(2):272-276.
[33]Otero G,Avila MA,de la Pe(?)a L,et al.Altered processing of precursor transcripts and increased levels of the subunit I of mitochondrial cytochrome c oxidase in Syrian hamster fetal cells initiated with ionizing radiation.Carcinogenesis.1997,18(8):1569-1575.
[34]Sugie K,Nishino I.Complex IV(cytochrome c oxidase).Nippon Rinsho,2002,60:490-494.
[35]Peng G,Bostinaa M,Radermacher M,et al.Biochemical and electron microscopic characterization of the F1 F0 ATPase from the hyperthermophilic eubacterium Aquifex aeolicus.FEBS Lett,2006,580:5934-5940.
[36]Burwick N R,Wahl M L,Fang J,et al.An inhibitor of the Flsubunit of ATPsynthase(IF1)modulates the activity of angiostatin on t he endothelial cell surface.J Biol Chem,2005,280:1740-1745.
[37]Herrero A,Barja G.Hydrogen peroxide production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice:site of free radical generation and mechanisms involved.Mech Aging Dev,1998,103:133-146.
[38]Villani G,Atardi G.In vivo control of respiration by cytochrome c oxidase in human cells[J].Free Radic Biol Med,2000,29(3-4):202-221.
[39]Chen Q,Crosby M,Almasan A.Redox regulation of apoptosis before and after cytochrome C release.Korean J Biol Sci,2003,7(1):129.
[40]高文祥,黄缄,高钰琪,等.低氧调节大鼠骨骼肌线粒体呼吸链复合体非协同性表达.第三军医大学学报,2008,30(3):223-225.
1 Jacobs L,Gerards M,Chinnery P,et al.Mol Hum Reprod,2007,13(3):149-154
2 陈道桢,薛文群,张丽珊.中国优生与遗传杂志,2005,13(4):7-8CHEN Daozhen,XUE Wenqun,ZHANG Lishan.Chin J Birth Health &Heredity,2005,13(4):7-8
3 Zhou S,Kassauei K,Cutler DJ,et al.J Mol Diagn,2006,8(4):476-482
4 TsaiLC,Lin CY,Lee JC,et al.Forensic Sci Int,2001,119(2):239-247
5 Richard SM,Baillietl G,P(?)ez GL,et al.Cancer research,2000,60(15):4231-4237
6 Pejivic T,Ladner D,Intengan M,et al.Eur J Cancer,2004,40(16):2519-2524
7 Lee HC,Yin PH,Lin JC,et al.Ann N Y Acad Sci,2005,1042:109-122
8 Marin-Garcia J,Zoubenko O,Goldenthal MJ.J Card Fail,2002,8(2):93-100
9 Janssen GM,Neu A,'t Hart LM,et al.Exp Clin Endocrinol Diabetes,2006,114(4):168-174
10 Salas A,Rasmussen EM,Lareu MV,et al.Forensic Sci Int,2001,124(2-3):97-103
11 Andr(?)asson H,Asp A,Alderborn A,et al.2002,32(1):124-126,128,130-133
12 Zupanic Pajnic I,Balazic J,Komel R.Int J Legal Med,2004,118(1):1-4
13 Shee CY,Chong MS,NgY,et al.Leg Med(Tokyo),2005,7(2):127-33
14 刘丽红,胡义德,钱海洪,等.第三军医大学学报,2007,29(10):889-891LIU Lihong,HU Yide,QIAN Haihong,et al.Acta Acad Med Mil Tertiae,2007,29(10):889-891
15 Habano W,Nakamura S,Sugai T.Oncogene,1998,17(15):1931-1937
16 Kose K,Hiyama T,Tanaka S,et al.Pathobiology,2006,73(2):93-97
17 Yoneyama H,Hara T,Kato Y,et al.Mol Cancer Res,2005,3(1):14-20
18 Wang Y,Liu VW,Tsang PC,et al.Int J Gynecol Cancer,2006,16(1):259-266
19 范德生,孙宁.现代肿瘤医学,2005,13(6):843-846FAN Desheng,SUN Ning.J Mod Oncol,2005,13(6):843-846
20 Murphy JE,Nugent S,Seymour C,et al.Mutat Res,2005,585(1-2):127-136
21 王洁,王学敏,龙建纲,等.第二军医大学学报,2005,26(6):615-617WANG Jie,WANG Xuemin,LONG Jiangang,et al.Acad J Sec Mil Med Univ,2005,26(6):615-617
22 Wilding CS,Cadwel K,Tawn EJ,et al.Radiat Res,2006,165(2):202-207
[1]Inoue JG,Miya M,Tsukamoto K,et al.Complete mitochondrial DNA sequence of Conger myriaster(teleostei:Anguilliformes):novel gene order for vertebrate genomes and the phylogenetic implications for anguilliform families[J].J Mol Evol,2001,52(4):0311-0320.
[2]Kaukonen J,Juselius JK,Tiranti V,et al.Role of adenine nucleotide translocator I in mtDNA maintenance[J].Science,2000,289(5480):782-785.
[3]谭小玲,柳君泽,曹利飞,等.长时间缺氧对大鼠脑皮质线粒体细胞色素氧化酶活性及亚基Ⅰ、Ⅳ蛋白表达的影响[J].中华航空航天医学杂志,2002,13(4):239-242.
[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[J].中国病理生理杂志,2000,16(10):879-882.
[5]柳君泽,高文祥,蔡明春,等.ATP浓度和缺氧暴露对大鼠脑线粒体RNA和蛋白质体外合成的影响[J].生理学报,2002,54(6):485-489.
[6]Sauleda J,Garcia PF,Wiesner RJ,et al.Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle of patients with chronic obstructive pulmonary disease[J].Am J Respir Crit Care Med,1998,157(5 Pt 1):1413-1417.
[7]Vijayasarathy C,Damle S,Prabu SK,et al.Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia[J].Eur J Biochem,2003,270(5):871-879.
[8]韩(王争)波,李凡,毛晓韵,等.线粒体DNA转录表达与胃癌发生关系的研究[J].中国肿瘤临床,2006,33(21):1205-1209.
[9]李建明,周红,蔡黔,等.过氧化氢对肠上皮细胞线粒体编码基因mRNA 的影响[J].第三军医大学学报,2002,24(3):267-270.
[10]谢燕,江海洪,龚茜芬,等.微波辐照对大鼠脑海马和皮层神经细胞线粒体超微结构及mtTFA mRNA表达的影响[J].中华劳动卫生职业病杂志,2004,22(2):104-107.
[11]余建华,钟敏,谢燕,等.微波辐照对大鼠海马COXⅠ、Ⅳ基因表达影响[J].中国公共卫生,2007,23(1):85-86.
[12]孙玉兰,胡义德,钱海洪.X射线诱导人肺腺癌A549细胞凋亡及线粒体DNA基因表达下调[J].中华放射医学与防护杂志,2007,27(5):433-437.
[13]柏干荣,陆松敏.线粒体DNA编码细胞色素氧化酶亚基基因的进展[J].国外医学分子生物学分册,2003,25(6):354-357.
[14]Goffart S,Wiesner RJ.Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis[J].Exp Physiol,2003,88(1):33-40.
[15]Berdanier CD.Mitochondrial gene expression:influence of nutrients and hormones[J].Exp Biol Med(Maywood),2006,231(10):1593-1601.
[16]Chu J,Tong M,de la Monte SM.Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons[J].Acta Neuropathol(Berl),2007,113(6):659-673.
[17]Berdanier CD,Everts HB,Hermoyian C,et al.Role of vitamin A in mitochondrial gene expression[J].Diabetes Res Clin Pract,2001,54(2):11-27.
[18]Everts HB.Nutrient-gene interactions:dietary vitamin A and mitochondrial gene .expression[J].IUBMB Life,2002,53(6):295-301.
[19]Dmitrenko V,Shostak K,Boyko O,et al.Reduction of the transcription level of the mitochondrial genome in human glioblastoma[J].Cancer Lett.2005,218(1):99-107.
[20]王洁,王学敏,龙建纲,等.人肝癌SMMC-7721细胞株部分线粒体基因表达 的研究[J].第二军医大学学报,2006,27(1):46-50.
[21]Yamamoto A,Horai S,Yuasa Y.Increased level of mitochondrial gene expression in polyps of familial polyposis coli patients[J].Cancer,1999,159(3):1100-1106.
[22]Manczak M,Park BS,Jung Y,et al.Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease:implications for early mitochondrial dysfunction and oxidative damage.Neuromolecular Med,2004,5(2):147-162.
[2] Ricci C, Pastukh V, Leonard J, et al. Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am J Physiol Cell Physiol, 2008, 294(2):C413-422.
[3] Khrapko K, Vijg J. Mitochondrial DNA mutations and aging: devils in the details? Trends Genet, 2009, 25(2):91-98.
[4] Camins A, Pallas M, Silvestre JS. Apoptotic mechanisms involved in neurodegenerative diseases: experimental and therapeutic approaches. Methods Find Exp Clin Pharmacol, 2008, 30(1):43-65.
[5] Urba(?)ska EM. Seizures evoked by mitochondrial toxin, 3-nitropropionic acid: new mechanism of epileptogenesis? Pol J Pharmacol, 2000, 52(1):55-57.
[6] Sompol P, Ittarat W, Tangpong J, et al. A neuronal model of Alzheimer's disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Neuroscience, 2008, 153(1):120-130.
[7] Parrella P, Xiao Y, Fliss M, et al. Detection of mitochondrial DNA mutations in primary breast cancer and fine - needle aspirates. Cancer Res, 2001, 61(20):7623-7626.
[8] Kumimoto H, Yamane Y, Nishimoto Y, et al. Frequent somatic mutations of mitochondrial DNAin esoghageal squamous cell carcinoma. Int J Cancer, 2004, 108(2): 228-231.
[9] Tong BC, Ha PK, Dhir K, et al. Mitochondrial DNA alterations in thyroid cancer. J Surg Oncol, 2003, 82(3): 170-173.
[10] Zhao YB, Yang HY, Zhang XW, et al. Mutation in D-loop region of mitochondrial DNA in gastric cancer and its significance. World J Gastroenterol, 2005, 11(21):3304-3306.
[11] Dmitrenko V, Shostak K, Boyko O, et al. Reduction of the transcription level of the mitochondrial genome in human glioblastoma. Cancer Lett, 2005,218(1): 99-107.
[12] Clarke SJ, Khaliulin I, Das M, et al. Inhibition of mitochondrial permeability transition pore opening by ischemic preconditioning is probably mediated by reduction of oxidative stress rather than mitochondrial protein phosphorylation. Circ Res, 2008, 102(9): 1082-1090.
[13] Akopova OV. The role of mitochondrial permeability transition pore in transmembrane Ca~(2+)-exchange in mitochondria. Ukr Biokhim Zh, 2008, 80(3):40-47.
[14] Wang ZB, Liu YQ, Zhang Y, et al. Reactive oxygen species, but not mitochondrial membrane potential, is associated with radiation-induced apoptosis of AHH-1 human lymphoblastoid cells. Cell Biol Int, 2007, 31(11):1353-1358.
[15] Knudson CM, Brown NM. Mitochondria potential, bax "activation," and programmed cell death. Methods Mol Biol, 2008,414: 95-108.
[16] Kose K, Hiyama T, Tanaka S, et al. Nuclear and mitochondrial DNA microsatellite instability in gastrointestinal stromal tumors. Pathobiology, 2006, 73(2):93-97.
[17] Meissner C, Bruse P, Mohamed SA, The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more? Exp Gerontol, 2008, 43(7):645-652.
[18] Behar DM, Blue-Smith J, Soria-Hernanz DF, et al. A novel 154-bp deletion in the human mitochondrial DNA control region in healthy individuals. Hum Mutat, 2008, 29(12):1387-1391.
[19] Malakhova L, Bezlepkin VG, Antipova V, et al. The increase in mitochondrial DNA copy number in the tissues of gamma-irradiated mice. Cell Mol Biol Lett, 2005, 10(4):721-732.
[20] R(o|¨)tig A, Munnich A. Genetic features of mitochondrial respiratory chain disorders. J Am Soc Nephrol, 2003, 14(12):2995-3007.
[21] Wallace DC. Mitochondrial disease in man and mouse. Science, 1999, 283 (5407):1482-1488.
[22]Ta kaoY agi,B youngBooSeo,SalvatoreDiBemardo,et al.NADH Dehydrogenases:From Basic Science to Biomedicine.Journal of B ioenergeticsa ndB iomembranes.2001,33(33):233-24.
[23]柏干荣,陆松敏.线粒体DNA编码细胞色素氧化酶亚基基因的进展.国外医学分子生物学分册,2003,25(6):354-357.
[24]Vijayasarathy C,Damle S,Prabu SK,et al.Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia.Eur J Biochem,2003,270(5):871-879.
[25]Shokolenko I,Venediktova N,Bochkareva A,et al.Oxidative stress induces degradation ofmitochondrial DNA.Nucleic Acids Res,2009,37(8):2539-2548.
[26]Wang L,Kuwahara Y,Li L,Baba T,Analysis of Common Deletion(CD)and a novel deletion of mitochondrial DNA induced by ionizing radiation.Int J Radiat Biol,2007,83(7):433-442.
[27]柳君泽,高文祥,蔡明春,等.ATP浓度和缺氧暴露对大鼠脑线粒体RNA和蛋白质体外合成的影响[J].生理学报,2002,54(6):485-489.
[28]Chu J,Tong M,de la Monte SM.Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons.Acta Neuropathol(Berl),2007,113(6):659-673.
[29]谢燕,江海洪,龚茜芬,等.微波辐照对大鼠脑海马和皮层神经细胞线粒体超微结构及mtTFA mRNA表达的影响.中华劳动卫生职业病杂志,2004,22(2):104-107.
[30]孙玉兰,胡义德,钱海洪.X射线诱导人肺腺癌A549细胞凋亡及线粒体DNA 基因表达下调.中华放射医学与防护杂志,2007,27(5):433-437.
[31]B.Gong,Q.Chen,A.Almasan.Ionizing radiation stimulates mitochondrial gene expression and activity.Radiat Res,1998,150:505-512.
[32]Roychoudhury P,Ghosh U,Bhattacharyya NP,et al.Activation of mitochondrial promoter P_(H)-binding protein in a radio-resistant Chinese hamster cell strain associated with Bcl-2.Biochem Biophys Res Commun,2006,350(2):272-276.
[33]Otero G,Avila MA,de la Pe(?)a L,et al.Altered processing of precursor transcripts and increased levels of the subunit I of mitochondrial cytochrome c oxidase in Syrian hamster fetal cells initiated with ionizing radiation.Carcinogenesis.1997,18(8):1569-1575.
[34]Sugie K,Nishino I.Complex IV(cytochrome c oxidase).Nippon Rinsho,2002,60:490-494.
[35]Peng G,Bostinaa M,Radermacher M,et al.Biochemical and electron microscopic characterization of the F1 F0 ATPase from the hyperthermophilic eubacterium Aquifex aeolicus.FEBS Lett,2006,580:5934-5940.
[36]Burwick N R,Wahl M L,Fang J,et al.An inhibitor of the Flsubunit of ATPsynthase(IF1)modulates the activity of angiostatin on t he endothelial cell surface.J Biol Chem,2005,280:1740-1745.
[37]Herrero A,Barja G.Hydrogen peroxide production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice:site of free radical generation and mechanisms involved.Mech Aging Dev,1998,103:133-146.
[38]Villani G,Atardi G.In vivo control of respiration by cytochrome c oxidase in human cells[J].Free Radic Biol Med,2000,29(3-4):202-221.
[39]Chen Q,Crosby M,Almasan A.Redox regulation of apoptosis before and after cytochrome C release.Korean J Biol Sci,2003,7(1):129.
[40]高文祥,黄缄,高钰琪,等.低氧调节大鼠骨骼肌线粒体呼吸链复合体非协同性表达.第三军医大学学报,2008,30(3):223-225.
1 Jacobs L,Gerards M,Chinnery P,et al.Mol Hum Reprod,2007,13(3):149-154
2 陈道桢,薛文群,张丽珊.中国优生与遗传杂志,2005,13(4):7-8CHEN Daozhen,XUE Wenqun,ZHANG Lishan.Chin J Birth Health &Heredity,2005,13(4):7-8
3 Zhou S,Kassauei K,Cutler DJ,et al.J Mol Diagn,2006,8(4):476-482
4 TsaiLC,Lin CY,Lee JC,et al.Forensic Sci Int,2001,119(2):239-247
5 Richard SM,Baillietl G,P(?)ez GL,et al.Cancer research,2000,60(15):4231-4237
6 Pejivic T,Ladner D,Intengan M,et al.Eur J Cancer,2004,40(16):2519-2524
7 Lee HC,Yin PH,Lin JC,et al.Ann N Y Acad Sci,2005,1042:109-122
8 Marin-Garcia J,Zoubenko O,Goldenthal MJ.J Card Fail,2002,8(2):93-100
9 Janssen GM,Neu A,'t Hart LM,et al.Exp Clin Endocrinol Diabetes,2006,114(4):168-174
10 Salas A,Rasmussen EM,Lareu MV,et al.Forensic Sci Int,2001,124(2-3):97-103
11 Andr(?)asson H,Asp A,Alderborn A,et al.2002,32(1):124-126,128,130-133
12 Zupanic Pajnic I,Balazic J,Komel R.Int J Legal Med,2004,118(1):1-4
13 Shee CY,Chong MS,NgY,et al.Leg Med(Tokyo),2005,7(2):127-33
14 刘丽红,胡义德,钱海洪,等.第三军医大学学报,2007,29(10):889-891LIU Lihong,HU Yide,QIAN Haihong,et al.Acta Acad Med Mil Tertiae,2007,29(10):889-891
15 Habano W,Nakamura S,Sugai T.Oncogene,1998,17(15):1931-1937
16 Kose K,Hiyama T,Tanaka S,et al.Pathobiology,2006,73(2):93-97
17 Yoneyama H,Hara T,Kato Y,et al.Mol Cancer Res,2005,3(1):14-20
18 Wang Y,Liu VW,Tsang PC,et al.Int J Gynecol Cancer,2006,16(1):259-266
19 范德生,孙宁.现代肿瘤医学,2005,13(6):843-846FAN Desheng,SUN Ning.J Mod Oncol,2005,13(6):843-846
20 Murphy JE,Nugent S,Seymour C,et al.Mutat Res,2005,585(1-2):127-136
21 王洁,王学敏,龙建纲,等.第二军医大学学报,2005,26(6):615-617WANG Jie,WANG Xuemin,LONG Jiangang,et al.Acad J Sec Mil Med Univ,2005,26(6):615-617
22 Wilding CS,Cadwel K,Tawn EJ,et al.Radiat Res,2006,165(2):202-207
[1]Inoue JG,Miya M,Tsukamoto K,et al.Complete mitochondrial DNA sequence of Conger myriaster(teleostei:Anguilliformes):novel gene order for vertebrate genomes and the phylogenetic implications for anguilliform families[J].J Mol Evol,2001,52(4):0311-0320.
[2]Kaukonen J,Juselius JK,Tiranti V,et al.Role of adenine nucleotide translocator I in mtDNA maintenance[J].Science,2000,289(5480):782-785.
[3]谭小玲,柳君泽,曹利飞,等.长时间缺氧对大鼠脑皮质线粒体细胞色素氧化酶活性及亚基Ⅰ、Ⅳ蛋白表达的影响[J].中华航空航天医学杂志,2002,13(4):239-242.
[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[J].中国病理生理杂志,2000,16(10):879-882.
[5]柳君泽,高文祥,蔡明春,等.ATP浓度和缺氧暴露对大鼠脑线粒体RNA和蛋白质体外合成的影响[J].生理学报,2002,54(6):485-489.
[6]Sauleda J,Garcia PF,Wiesner RJ,et al.Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle of patients with chronic obstructive pulmonary disease[J].Am J Respir Crit Care Med,1998,157(5 Pt 1):1413-1417.
[7]Vijayasarathy C,Damle S,Prabu SK,et al.Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia[J].Eur J Biochem,2003,270(5):871-879.
[8]韩(王争)波,李凡,毛晓韵,等.线粒体DNA转录表达与胃癌发生关系的研究[J].中国肿瘤临床,2006,33(21):1205-1209.
[9]李建明,周红,蔡黔,等.过氧化氢对肠上皮细胞线粒体编码基因mRNA 的影响[J].第三军医大学学报,2002,24(3):267-270.
[10]谢燕,江海洪,龚茜芬,等.微波辐照对大鼠脑海马和皮层神经细胞线粒体超微结构及mtTFA mRNA表达的影响[J].中华劳动卫生职业病杂志,2004,22(2):104-107.
[11]余建华,钟敏,谢燕,等.微波辐照对大鼠海马COXⅠ、Ⅳ基因表达影响[J].中国公共卫生,2007,23(1):85-86.
[12]孙玉兰,胡义德,钱海洪.X射线诱导人肺腺癌A549细胞凋亡及线粒体DNA基因表达下调[J].中华放射医学与防护杂志,2007,27(5):433-437.
[13]柏干荣,陆松敏.线粒体DNA编码细胞色素氧化酶亚基基因的进展[J].国外医学分子生物学分册,2003,25(6):354-357.
[14]Goffart S,Wiesner RJ.Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis[J].Exp Physiol,2003,88(1):33-40.
[15]Berdanier CD.Mitochondrial gene expression:influence of nutrients and hormones[J].Exp Biol Med(Maywood),2006,231(10):1593-1601.
[16]Chu J,Tong M,de la Monte SM.Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons[J].Acta Neuropathol(Berl),2007,113(6):659-673.
[17]Berdanier CD,Everts HB,Hermoyian C,et al.Role of vitamin A in mitochondrial gene expression[J].Diabetes Res Clin Pract,2001,54(2):11-27.
[18]Everts HB.Nutrient-gene interactions:dietary vitamin A and mitochondrial gene .expression[J].IUBMB Life,2002,53(6):295-301.
[19]Dmitrenko V,Shostak K,Boyko O,et al.Reduction of the transcription level of the mitochondrial genome in human glioblastoma[J].Cancer Lett.2005,218(1):99-107.
[20]王洁,王学敏,龙建纲,等.人肝癌SMMC-7721细胞株部分线粒体基因表达 的研究[J].第二军医大学学报,2006,27(1):46-50.
[21]Yamamoto A,Horai S,Yuasa Y.Increased level of mitochondrial gene expression in polyps of familial polyposis coli patients[J].Cancer,1999,159(3):1100-1106.
[22]Manczak M,Park BS,Jung Y,et al.Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease:implications for early mitochondrial dysfunction and oxidative damage.Neuromolecular Med,2004,5(2):147-162.