Mitochondrial Proteomics Alterations in Rat Hearts Following Ischemia/reperfusion and Diazoxide Post‑conditioning

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2020 Dec 23

PMID 33355377

Citations 6

Authors

Yunchao Pan

Yuan Wang

Wenyan Shi

Yun Liu

Song Cao

Tian Yu

Affiliations

Soon will be listed here.

Abstract

Diazoxide post‑conditioning (D‑Post) has been shown to be effective in alleviating myocardial ischemia/reperfusion (I/R) injury; however, the specific mechanisms are not fully understood. In the present study, isolated rat hearts were subjected to I/R injury and D‑Post. The mitochondria were extracted, and mitochondrial protein expression was detected in normal, I/R and D‑Post hearts using two‑dimensional electrophoresis and matrix‑assisted laser desorption ionization‑time of flight mass spectrometry. Differentially expressed proteins were then identified using comparative proteomics. In total, five differentially expressed proteins were identified between the I/R and D‑Post hearts. Compared with the I/R hearts, the expression of NADH dehydrogenase (ubiquinone) flavoprotein 1 (NDUFV1), NADH‑ubiquinone oxidoreductase 75 kDa subunit (NDUFS1), 2‑oxoglutarate dehydrogenase (OGDH) and ATP synthase α subunit (isoform CRA_b, gi|149029482) was increased in D‑Post hearts. In addition, the expression of another isoform of ATP synthase α subunit (isoform CRA_c, gi|149029480) was decreased in the D‑Post group compared with the I/R group. The expression profiles of NDUFV1, NDUFS1 and OGDH in the two groups were further validated via western blotting. The five differentially expressed proteins may be protective effectors in D‑Post, as well as potential targets for the treatment of cardiac I/R injury.

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References

Yang L, Xie P, Wu J, Yu J, Yu T, Wang H . Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1. Am J Transl Res. 2016; 8(10):4415-4424. PMC: 5095334. View

Meng W, Xu Y, Li D, Zhu E, Deng L, Liu Z . Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury. Biomed Pharmacother. 2017; 88:1090-1097. DOI: 10.1016/j.biopha.2017.01.151. View

Bagheri F, Khori V, Alizadeh A, Khalighfard S, Khodayari S, Khodayari H . Reactive oxygen species-mediated cardiac-reperfusion injury: Mechanisms and therapies. Life Sci. 2016; 165:43-55. DOI: 10.1016/j.lfs.2016.09.013. View

Liu Y, Sato T, ORourke B, Marban E . Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?. Circulation. 1998; 97(24):2463-9. DOI: 10.1161/01.cir.97.24.2463. View

Flameng W, Borgers M, Daenen W, Stalpaert G . Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man. J Thorac Cardiovasc Surg. 1980; 79(3):413-24. View

Mailloux R, Gardiner D, OBrien M . 2-Oxoglutarate dehydrogenase is a more significant source of O2(·-)/H2O2 than pyruvate dehydrogenase in cardiac and liver tissue. Free Radic Biol Med. 2016; 97:501-512. DOI: 10.1016/j.freeradbiomed.2016.06.014. View

Cao S, Liu Y, Sun W, Zhao L, Zhang L, Liu X . Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis. Oxid Med Cell Longev. 2015; 2015:756576. PMC: 4485557. DOI: 10.1155/2015/756576. View

Kaski J, Crea F, Gersh B, Camici P . Reappraisal of Ischemic Heart Disease. Circulation. 2018; 138(14):1463-1480. DOI: 10.1161/CIRCULATIONAHA.118.031373. View

Paiva S, Agbulut O . MiRroring the Multiple Potentials of MicroRNAs in Acute Myocardial Infarction. Front Cardiovasc Med. 2017; 4:73. PMC: 5701911. DOI: 10.3389/fcvm.2017.00073. View

10.

Yu T, Fu X, Liu X, Yu Z . Protective effects of pinacidil hyperpolarizing cardioplegia on myocardial ischemia reperfusion injury by mitochondrial KATP channels. Chin Med J (Engl). 2012; 124(24):4205-10. View

11.

Yu T, Yu Z, Liu X, Yang S, Ye Y . Myocardial protection with pinacidil induced hyperpolarized arrest during cardiopulmonary bypass. Chin Med J (Engl). 2002; 114(12):1245-8. View

12.

Bjorkman K, Sofou K, Darin N, Holme E, Kollberg G, Asin-Cayuela J . Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1. Mitochondrion. 2015; 21:33-40. DOI: 10.1016/j.mito.2015.01.003. View

13.

Caricati-Neto A, Errante P, Menezes-Rodrigues F . Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection. Int J Mol Sci. 2019; 20(16). PMC: 6720817. DOI: 10.3390/ijms20164002. View

14.

Chen Q, Younus M, Thompson J, Hu Y, Hollander J, Lesnefsky E . Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 2018; 314(4):H787-H795. PMC: 5966772. DOI: 10.1152/ajpheart.00531.2017. View

15.

Veys K, Alvarado-Diaz A, De Bock K . Measuring Glycolytic and Mitochondrial Fluxes in Endothelial Cells Using Radioactive Tracers. Methods Mol Biol. 2018; 1862:121-136. DOI: 10.1007/978-1-4939-8769-6_9. View

16.

Kim N, Lee Y, Kim H, Joo H, Youm J, Park W . Potential biomarkers for ischemic heart damage identified in mitochondrial proteins by comparative proteomics. Proteomics. 2006; 6(4):1237-49. DOI: 10.1002/pmic.200500291. View

17.

Yang L, Yu T . Prolonged donor heart preservation with pinacidil: the role of mitochondria and the mitochondrial adenosine triphosphate-sensitive potassium channel. J Thorac Cardiovasc Surg. 2010; 139(4):1057-63. DOI: 10.1016/j.jtcvs.2009.10.042. View

18.

Henn M, Janjua M, Kanter E, Makepeace C, Schuessler R, Nichols C . Adenosine Triphosphate-Sensitive Potassium Channel Kir Subunits Implicated in Cardioprotection by Diazoxide. J Am Heart Assoc. 2015; 4(8):e002016. PMC: 4599460. DOI: 10.1161/JAHA.115.002016. View

19.

Pagliaro P, Femmino S, Popara J, Penna C . Mitochondria in Cardiac Postconditioning. Front Physiol. 2018; 9:287. PMC: 5879113. DOI: 10.3389/fphys.2018.00287. View

20.

Cao S, Liu Y, Wang H, Mao X, Chen J, Liu J . Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts. PeerJ. 2016; 4:e1706. PMC: 4768691. DOI: 10.7717/peerj.1706. View