[1]田卫 饶小娇 高萌 肖书娜.PGC-1α/Nrf1介导的线粒体生物合成通路在过氧化氢诱导的心肌细胞衰老中的作用机制[J].心血管病学进展,2024,(10):955.[doi:10.16806/j.cnki.issn.1004-3934.2024.10.017]
　TIAN Wei,RAO Xiaojiao,GAO Meng,et al.The Role of PGC-1/Nrf1 Mediated Mitochondrial Biosynthesis Pathway in Hydrogen Peroxide-Induced Cardiomyocyte Senescence[J].Advances in Cardiovascular Diseases,2024,(10):955.[doi:10.16806/j.cnki.issn.1004-3934.2024.10.017]
点击复制

PGC-1α/Nrf1介导的线粒体生物合成通路在过氧化氢诱导的心肌细胞衰老中的作用机制()
分享到：

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年10期
页码:
955
栏目:
论著
出版日期:
2024-10-25

文章信息/Info

Title:
The Role of PGC-1/Nrf1 Mediated Mitochondrial Biosynthesis Pathway in Hydrogen Peroxide-Induced Cardiomyocyte Senescence
作者:
田卫 饶小娇 高萌 肖书娜
?华中科技大学同济医学院附属梨园医院心血管内科,湖北 武汉 430000)
Author(s):
TIAN Wei; RAO Xiaojiao; GAO Meng; XIAO Shuna
(Department of Cardiovascular,Liyuan Hospital of Tongji Medical College OF Huazhong University of Science and Technology,Wuhan 430000,Hubei,China)
关键词:
心肌细胞; 衰老; p21; p53; PGC-1α/Nrf1通路; 线粒体
Keywords:
Cardiomyocytes;  a ging;  p21;  p53;  PGC-1/Nrf1 pathway;  mitochondria
DOI:
10.16806/j.cnki.issn.1004-3934.2024.10.017
摘要:
目的 探究PGC-1α/Nrf1介导的线粒体生物合成通路在H2O2诱导的心肌细胞衰老中的作用及可能机制。方法 培养H9c2心肌细胞，根据实验设计分为对照组、衰老组、PGC-1α激活组，Western blotting检测心肌细胞中p21、p53、PGC-1α、Nrf1的蛋白水平，RT-qPCR检测心肌细胞中p21、p53、PGC-1α、Nrf1的mRNA水平，免疫荧光染色检测p53与PGC-1α共表达水平，试剂盒检测心肌细胞中超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、丙二醛（MDA）、活性氧（ROS）及腺苷三磷酸（ATP）水平，线粒体膜电位检测试剂盒检测线粒体膜电位（ΔΨm）。结果 与对照组相比，衰老组心肌细胞中衰老标志蛋白p21、p53蛋白及mRNA水平增加（P<0.05），线粒体生物合成通路蛋白PGC-1α、Nrf1蛋白及mRNA水平减少；与衰老组相比，PGC-1α激活组p21、p53蛋白及mRNA水平减少（P<0.05），PGC-1α、Nrf1蛋白及mRNA水平增加（P<0.05）。与对照组相比，衰老组心肌细胞SOD、GSH含量减少（P<0.05），MDA、ROS含量增加（P<0.05），细胞ΔΨm下降（P<0.05），ATP含量减少（P<0.05）；与衰老组相比，PGC-1α激活组SOD、GSH含量增加（P<0.05），MDA、ROS含量减少（P<0.05），PGC-1α激活组ΔΨm增加（P<0.05），ATP含量增加（P<0.05）。结论 PGC-1α/Nrf1介导的线粒体生物合成通路在H2O2诱导的心肌细胞衰老中发挥重要作用，激活PGC-1α/Nrf1通路可通过改善氧化应激水平改善心肌细胞的衰老。
Abstract:
Objective To investigate the role of PGC-1α/Nrf1 mediated mitochondrial biosynthesis pathway in H 2O2-induced cardiomyocyte senescence and its possible mechanism. Methods H9c2 cardiomyocytes were cultured and divided into control group ,senescence group and PGC-1α activated group according to the experimental design. Western blotting detected the protein levels of p21,p53,PGC-1α and Nrf1 in the cardiomyocytes. mRNA levels of p21,p53,PGC-1α and Nrf1 in cardiomyocytes were detected by RT-qPCR,co-expression levels of p53 and PGC-1α were detected by immunofluorescence staining,superoxide dismutase (SOD),glutathione (GSH),malondialdehyde (MDA),reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels in cardiomyocytes were detected by kit. Mitochondrial membrane potential test kit was used to detect mitochondrial membrane potential (ΔΨm). Results Compared with the control group ,the levels of senescence marker proteins p21 and p53 protein and mRNA in cardiomyocytes of senescent group were increased(P<0.05),mitochondrial biosynthesis pathway proteins PGC-1α,Nrf1 protein and mRNA levels decreased. Compared with aging group,the levels of p21 and p53 protein and mRNA in PGC-1α activated group were decreased(P<0.05),PGC-1α,Nrf1 protein and mRNA levels increased(P<0.05). Compared with control group,SOD and GSH contents of cardiomyocytes in senescent group decreased(P<0.05),MDA and ROS contents increased(P<0.05),cell ΔΨm decreased(P<0.05),ATP content decreased (P<0.05). Compared with aging group,the contents of SOD and GSH in PGC-1α activated group were increased(P<0.05),MDA and ROS contents decreased(P<0.05),ΔΨm increased in PGC-1α activation group( P<0.05),ATP content increased(P<0.05). Conclusion PGC-1α/Nrf1 mediated mitochondrial biosynthesis pathway plays an important role in H 2O2-induced cardiomyocyte senescence,activation of PGC-1α/Nrf1 pathway can improve the senescence of cardiomyocytes by improving the level of oxidative stress

参考文献/References:

[1].Virani SS,Alonso A,Benjamin EJ,et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association[J]. Circulation,2020,141(9):e139-e596.
[2].Ma S,Sun S,Li J,et al. Single-cell transcriptomic atlas of primate cardiopulmonary aging[J]. Cell Res,2021,31(4):415-432.
[3].Halling JF,Pilegaard H. PGC-1α-mediated regulation of mitochondrial function and physiological implications[J]. Appl Physiol Nutr Metab,2020,45(9):927-936.
[4].Li Y,Feng YF,Liu XT,et al. Songorine promotes cardiac mitochondrial biogenesis via Nrf2 induction during sepsis[J]. Redox Biol,2021,38:101771.
[5].Li Q,Huang K,Ma T,et al. Metoprolol protects against arginine vasopressin-induced cellular senescence in H9c2 cardiomyocytes by regulating the Sirt1/p53/p21 axis[J]. Cardiovasc Toxicol,2022,22(2):99-107.
[6].Zhuang Y,Li T,Xiao H,et al. LncRNA-H19 drives cardiomyocyte senescence by targeting miR-19a/socs1/p53 axis[J]. Front Pharmacol,2021,12:631835.
[7].Wang J,Li S,Wang J,et al. Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function[J]. Aging (Albany NY),2020,12(1):650-671.
[8].Zhang Y,Liu S,Li X,et al. Protective effect of fasudil on hydrogen peroxide-induced oxidative stress injury of H9C2 cardiomyocytes[J]. Dis Markers,2021,2021:8177705.
[9].Ghimire A,Howlett SE. An acute estrogen receptor agonist enhances protective effects of cardioplegia in hearts from aging male and female mice[J]. Exp Gerontol,2020,141:111093.
[10].Liberale L,Badimon L,Montecucco F,et al. Inflammation,aging,and cardiovascular disease: JACC review topic of the week[J]. J Am Coll Cardiol,2022,79(8):837-847.
[11].Moturi S,Ghosh-Choudhary SK,Finkel T. Cardiovascular disease and the biology of aging[J]. J Mol Cell Cardiol,2022167:109-117.
[12].Lingyan Z,Yihong W,Youhua W,et al. Protective efficacy of Shenge San on mitochondria in H9c2 cardiomyocytes[J]. J Tradit Chin Med,2022,42(6):892-899.
[13].Yeo D,Kang C,Gomez-Cabrera MC,et al. Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1α overexpression in vivo[J]. Free Radic Biol Med,2019,130:361-368.
[14].Sanz MN,Grimbert L,Moulin M,et al. Inducible cardiac-specific deletion of sirt1 in male mice reveals progressive cardiac dysfunction and sensitization of the heart to pressure overload[J]. Int J Mol Sci,2019,20(20):5005.
[15].Lee JJ,Ng SC,Hsu JY,et al. Galangin reverses H2O2-induced dermal fibroblast senescence via SIRT1-PGC-1α/Nrf2 signaling[J]. Int J Mol Sci,2022,23(3):1387.

相似文献/References:

[1]黄淮滨 刘甲兴.肥厚型心肌病治疗新靶点——钙脱敏治疗[J].心血管病学进展,2019,(7):1047.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.021]
　HUANG HuaibinLIU Jiaxing.A Novel Target for Therapy in Hypertrophic Cardiomyopathy: Ca2+ desensitizer[J].Advances in Cardiovascular Diseases,2019,(10):1047.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.021]
[2]杜冲 韦文 李亚飞 王连生.心肌梗死后心肌细胞内源再生的研究进展[J].心血管病学进展,2020,(4):395.[doi:10.16806/j.cnki.issn.1004-3934.2020.04.017]
　DU Chong,WEI Tianwen,LI Yafei,et al.Endogenous Regeneration of Myocardial Cells after Myocardial Infarction[J].Advances in Cardiovascular Diseases,2020,(10):395.[doi:10.16806/j.cnki.issn.1004-3934.2020.04.017]
[3]谭海鹏 高金峰 李琦玉 王樵梓 张宁 陈婧 黄浙勇.MicroRNA促进心肌细胞再生机制的研究进展[J].心血管病学进展,2020,(7):698.[doi:10.16806/j.cnki.issn.1004-3934.2020.07.007]
　TAN Haipeng,GAO Jinfeng,LI Qiyu,et al.Mechanism of MicroRNA Promoting Cardiomyocyte Regeneration[J].Advances in Cardiovascular Diseases,2020,(10):698.[doi:10.16806/j.cnki.issn.1004-3934.2020.07.007]
[4]张伟 权大君 向杰 黄从新.人源性诱导多潜能干细胞向心肌细胞分化的实验研究[J].心血管病学进展,2020,(7):753.[doi:10.16806/j.cnki.issn.1004-3934.2020.07.020]
　ZHANG Wei,QUAN Dajun,XIANG Jie,et al.Experimental Research on Differentiation of Human Induced Pluripotent Stem Cells into Cardiomyocytes[J].Advances in Cardiovascular Diseases,2020,(10):753.[doi:10.16806/j.cnki.issn.1004-3934.2020.07.020]
[5]武韧 常贵全 孙凤起 李鸿珠.硫化氢对糖尿病心肌病的保护作用[J].心血管病学进展,2021,(1):52.[doi:10.16806/j.cnki.issn.1004-3934.2021.01.000]
　WU Ren,CHANG Guiquan,SUN Fengqi,et al.Protective Effect of Hydrogen Sulfide in Diabetic Cardiomyopathy[J].Advances in Cardiovascular Diseases,2021,(10):52.[doi:10.16806/j.cnki.issn.1004-3934.2021.01.000]
[6]魏士雄 孙赫.过氧化物酶体增殖物激活受体激动剂在心肌梗死中的作用机制研究进展[J].心血管病学进展,2021,(12):1110.[doi:10.16806/j.cnki.issn.1004-3934.2021.12.013]
　WEI Shixiong,SUN He.Action Mechanism of Peroxisome Proliferator-activated Receptor Agonist in Myocardial Infarction[J].Advances in Cardiovascular Diseases,2021,(10):1110.[doi:10.16806/j.cnki.issn.1004-3934.2021.12.013]
[7]傅义程 张福春 刘慧琳.表观遗传年龄与衰老和心血管疾病的研究进展[J].心血管病学进展,2022,(7):590.[doi:10.16806/j.cnki.issn.1004-3934.2022.07.000]
　FU Yicheng,ZHANG Fuchun,LIU Huilin.Epigenetic Age with Senescence and Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2022,(10):590.[doi:10.16806/j.cnki.issn.1004-3934.2022.07.000]
[8]曹兴丹 陈子仪 宋小刚 张玉秀 陈敏 汤吉超 李萍萍 陈永清 荆哲.EMRE在高糖环境中的变化对心肌细胞凋亡机制的研究[J].心血管病学进展,2022,(10):953.[doi:10.16806/j.cnki.issn.1004-3934.2022.10.020]
　CAO XingdanCHEN ZiyiSONG XiaogangZHANG YuxiuCHEN MinTANG JichaoLI PingpingCHEN YongqingJING Zhe.Effect of High Glucose-Induced EMRE Expressions Changes on?yocardial Apoptosis[J].Advances in Cardiovascular Diseases,2022,(10):953.[doi:10.16806/j.cnki.issn.1004-3934.2022.10.020]
[9]徐建昌 王晞.衰老在心房颤动中的作用及抗衰老治疗研究进展[J].心血管病学进展,2022,(12):1088.[doi:10.16806/j.cnki.issn.1004-3934.2022.12.007]
　XU Jianchang,WANG Xi.Role of Aging and Therapeutic of Anti-Aging in Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2022,(10):1088.[doi:10.16806/j.cnki.issn.1004-3934.2022.12.007]
[10]孙悦 付松波 李亦兰.心肌细胞铁死亡及其检测方法[J].心血管病学进展,2023,(2):167.[doi:10.16806/j.cnki.issn.1004-3934.2023.02.016]
　SUN Yue,FU Songbo,LI Yilan.Methods for the Detection of Ferroptosis in Cardiomyocytes[J].Advances in Cardiovascular Diseases,2023,(10):167.[doi:10.16806/j.cnki.issn.1004-3934.2023.02.016]
[11]王思博 经鹏 杨彤彤 赵迪 王连生.蛋白激酶mTOR调控心肌细胞衰老的机制研究进展[J].心血管病学进展,2024,(5):420.[doi:10.16806/j.cnki.issn.1004-3934.2024.05.009]
　WANG Sibo,JING Peng,YANG Tongtong,et al.Mechanisms of Protein Kinase mTOR Regulating Cardiomyocyte Aging[J].Advances in Cardiovascular Diseases,2024,(10):420.[doi:10.16806/j.cnki.issn.1004-3934.2024.05.009]

更新日期/Last Update: 2024-11-01