Rhein alleviates myocardial ischemic injury by inhibiting mitochondrial division, activating mitochondrial autophagy and suppressing myocardial cell apoptosis through the Drp1/Pink1/Parkin pathway

被引:4
作者
Li, Hanqing [1 ]
Jia, Yan [1 ]
Yao, Daomin [2 ]
Gao, Ming [3 ]
Wang, Lijun [1 ]
Liu, Jing [1 ]
机构
[1] Nanjing Univ, Jinling Hosp, Affiliated Hosp, Dept Cardiol,Med Sch, 305 East Zhong Shan Rd, Nanjing 210002, Peoples R China
[2] Nanjing Univ Chinese Med, Dept Pharmacol, Nanjing 210023, Peoples R China
[3] Nanjing Univ, Jinling Hosp, Dept Pharm, Affiliated Hosp,Med Sch, 305 East Zhong Shan Rd, Nanjing 210002, Peoples R China
基金
中国国家自然科学基金;
关键词
Acute myocardial infarction; Mitochondrial fission; Mitophagy; Apoptosis; Traditional Chinese medicine; Rhein; FISSION; PARKIN; MITOPHAGY;
D O I
10.1007/s11033-023-09154-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
BackgroundRhein, which has antioxidant and anti-inflammatory response properties, is a beneficial treatment for different pathologies. However, the mechanism by which rhein protects against myocardial ischemic injury is poorly understood.Methods and resultsTo establish an acute myocardial infarction (AMI) rat model, we performed left anterior descending (LAD) ligation. Sprague-Dawley rats were randomly divided into four groups: sham, AMI, AMI + rhein (AMI + R), and AMI + mitochondrial fission inhibitor (AMI + M). The extent of myocardial injury was evaluated by TTC staining, serum myocardial injury markers, and HE and Masson staining. Cardiac mitochondria ultrastructure was visualized by transmission electron microscopy. TUNEL assay and flow cytometry analysis were used to estimate cell apoptosis. Protein expression levels were measured by Western blotting. In vitro, the efficacy of rhein was assessed in H9c2 cells under hypoxic condition. Our results revealed that rats with AMI exhibited increased infarct size and indicators of myocardial damage, along with activation of Drp1-dependent mitochondrial fission, decreased mitophagy and increased apoptosis rates. However, pretreatment with rhein significantly reversed these effects and demonstrated similar efficacy to Mdivi-1. Furthermore, rhein pretreatment protected against myocardial ischemic injury by inhibiting mitochondrial fission, as evidenced by decreased Drp1 expression. It also enhanced mitophagy, as indicated by increased expression of Beclin1, Pink1 and Parkin, an increased LC3-II/LC3-I ratio and increased formation of autolysosomes. Additionally, rhein pretreatment mitigated apoptosis in AMI. These results were also confirmed in vitro in H9c2 cells.ConclusionOur results demonstrate that rhein pretreatment exerts cardioprotective effects against myocardial ischemic injury via the Drp1/Pink1/Parkin pathway.
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页数:13
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共 43 条
  • [1] Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment
    Ajoolabady, Amir
    Chiong, Mario
    Lavandero, Sergio
    Klionsky, Daniel J.
    Ren, Jun
    [J]. TRENDS IN MOLECULAR MEDICINE, 2022, 28 (10) : 836 - 849
  • [2] Epidemiology of cardiovascular disease in young individuals
    Andersson, Charlotte
    Vasan, Ramachandran S.
    [J]. NATURE REVIEWS CARDIOLOGY, 2018, 15 (04) : 230 - 240
  • [3] Mitochondrial quality control in cardiac ischemia/reperfusion injury: new insights into mechanisms and implications
    Bai, Yang
    Wu, Jinjing
    Yang, Zhenyu
    Wang, Xu'an
    Zhang, Dongni
    Ma, Jun
    [J]. CELL BIOLOGY AND TOXICOLOGY, 2023, 39 (01) : 33 - 51
  • [4] Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis
    Barbosa, David Monteiro
    Fahlbusch, Pia
    de Wiza, Daniella Herzfeld
    Jacob, Sylvia
    Kettel, Ulrike
    Al-Hasani, Hadi
    Krueger, Martina
    Ouwens, D. Margriet
    Hartwig, Sonja
    Lehr, Stefan
    Kotzka, Jorg
    Knebel, Birgit
    [J]. SCIENTIFIC REPORTS, 2020, 10 (01)
  • [5] Molecular Mechanisms of Mitochondrial Quality Control in Ischemic Cardiomyopathy
    Chang, Xing
    Liu, Ruxiu
    Li, Ruibing
    Peng, Youyou
    Zhu, Pingjun
    Zhou, Hao
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2023, 19 (02): : 426 - 448
  • [6] DUSP12 ameliorates myocardial ischemia-reperfusion injury through HSPB8-induced mitophagy
    Cheng, Jing
    Ji, Meihua
    Jing, Haijuan
    Lin, Hongqi
    [J]. JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2023, 37 (05)
  • [7] Mdivi-1 alleviates cardiac fibrosis post myocardial infarction at infarcted border zone, possibly via inhibition of Drp1-Activated mitochondrial fission and oxidative stress
    Ding, Jie
    Zhang, Zhihao
    Li, Sui
    Wang, Wei
    Du, Tingyi
    Fang, Qin
    Wang, Yan
    Wang, Dao Wen
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2022, 718
  • [8] DRP1-Mediated Mitophagy: Safeguarding Obese Hearts From Cardiomyopathy
    Fang, Xi
    Gustafsson, Asa B.
    [J]. CIRCULATION RESEARCH, 2023, 133 (01) : 22 - 24
  • [9] Mitophagy as a mitochondrial quality control mechanism in myocardial ischemic stress: from bench to bedside
    Fu, Tong
    Ma, Yanchun
    Li, Yan
    Wang, Yingwei
    Wang, Qi
    Tong, Ying
    [J]. CELL STRESS & CHAPERONES, 2023, 28 (03) : 239 - 251
  • [10] Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury
    Garcia-Nino, Wylly Ramses
    Zazueta, Cecilia
    Buelna-Chontal, Mabel
    Silva-Palacios, Alejandro
    [J]. LIFE-BASEL, 2021, 11 (11):