Overexpression of PLK1 relieved the myocardial ischemia-reperfusion injury of rats through inducing the mitophagy and regulating the p-AMPK/FUNDC1 axis

Abstract

Myocardial cell injury caused by myocardial ischemia and reperfusion is one of the main causes of the occurrence and development of heart disease. Recent study has shown that inducing mitophagy of cardiomyocytes is a crucial method to alleviate ischemia-reperfusion injury. While, Polo-like kinase 1 (PLK1) can induce the mitophagy of breast cancer cells. Moreover, PLK1 was able to promote the expression of p-AMPK and FUNDC1, which are the protective factors for myocardium. Therefore, the mouse model of ischemia/reperfusion was established and the effect of PLK1 on ischemia reperfusion induced myocardial damage was investigated. The PLK1 was overexpressed in H9c2 cells and rat model of ischemia/reperfusion. Ischemia reperfusion inhibited the expression of PLK1. While overexpression of PLK1 relieved the myocardial infarction and myocardium apoptosis through inducing mitophagy in rats model of ischemia reperfusion. In vitro, the H9c2 cells overexpressing the PLK1 were treated with the hypoxia and reoxygenation and the apoptosis, survival rate and expression of mitophagy-related proteins of H9c2 cells were detected using the flow cytometry, CCK-8 assay and western blotting. The results reveled that overexpression of PLK1 alleviated the hypoxia and reoxygenation induced apoptosis of H9c2 cells and promoted the expression of mitophagy-related proteins. In addition, enhanced PLK1 expression promoted the expression of p-AMPK and FUNDC1 in H9c2 cells. However, the inhibition of FUNDC1 abolished the positive effect of PLK1 on H9c2 cells mentioned above. In conclusion, PLK1 alleviated the ischemia reperfusion induced myocardial damage by inducing the mitophagy in a p-AMPK/FUNDC1 signaling dependent pathway.

Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression

“…For example, long non-coding RNA myocardial infarction-associated transcript (MIAT) is discovered to weaken reduce I/R injury via reducing cardiomyocytes apoptosis [ 32 ]. Polo-like kinase 1 (PLK1) is demonstrated to alleviate I/R-caused myocardial apoptosis via promoting mitophagy [ 6 ]. Previous studies demonstrated that EGCG could inhibit cardiomyocytes apoptosis in I/R-stimulated rat model [ 18 , 33 ].…”

“…Acute and persistent ischemia will result in irreversible damage to the heart, and even cause myocardial infarction (MI), a major reason for mortality of people with coronary artery disorder [ 3 , 4 ]. Besides, as the main therapeutic strategy for ischemia, blood reperfusion also can damage cardiomyocytes, termed ‘reperfusion-injury’ [ 5 , 6 ]. Studying the molecular mechanism related to myocardial ischemia/reperfusion (I/R) injury and searching strategies methods that can weaken I/R-resulted cardiomyocytes damage is believed to have great value for prevention and therapy of coronary artery disorder.…”

Tubeimoside I Ameliorates Myocardial Ischemia‐Reperfusion Injury through SIRT3‐Dependent Regulation of Oxidative Stress and Apoptosis

“…H9c2 cells were cultivated as described previously [ 33 ]. Simulated ischemia-reperfusion (SIR) was performed using ischemic DMEM (DMEM without glucose and serum and dissolved oxygen in the culture media was expelled by filling nitrogen) and low-oxygen incubator as described previously [ 33 – 37 ]. Briefly, H9c2 cells were inoculated and cultivated for 24 h, starved for 4 h, and pretreated with TBM for 1 h. Then, cells were treated in ischemic DMEM and incubated in low-oxygen incubator (Thermo Scientific, Waltham, MA, USA) for 2 h (air conditions are 5% CO 2 , 1% O 2 , and 94% N 2 ) and reperfusion was initiated by changing ischemic DMEM into complete DMEM (containing 4.5 g glucose and 10% FBS) and incubated using 95% air+5% CO 2 .…”

FUNDC1: A Promising Mitophagy Regulator at the Mitochondria-Associated Membrane for Cardiovascular Diseases

“…Genetic deletion of CK2α was also proved by Zhou et al to protect cardiomyocytes from I/R injury via decreased Ser13 phosphorylation of FUNDC1 to promote mitophagy and to prevent mitochondrial damage and apoptosis (Zhou et al, 2018a). In addition, some kinases, such as mammalian STE20-like kinase 1 (Mst1) and polo-like kinase 1 (PLK1), have also been associated with FUNDC1-mediated mitophagy in vivo and in vitro under I/R stimuli (Yu et al, 2019;Mao et al, 2021).…”