Role of poly(ADP-ribose) polymerases-1-mediated blockade of autophagy in ischemia/reperfusion injury of rat cardiomyocytes / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of poly(ADP-ribose) polymerases-1 (PARP-1)-mediated blockade of autophagic flow in myocardial ischemia-reperfusion injury.</p><p><b>METHODS</b>H9c2 cells, a rat cardiac myocyte line, were divided into control group, hypoxia/ reoxygenation model group (H/R group), PARP-1 inhibitor (PJ34) group, and PJ34 + H/R group. The total protein was extracted from the cells in each group to detect the expressions of pADPr, Bax, the DNA damage marker protein p-YH2ax, and autophagic flow-associated proteins LC3BⅡ/LC3Ⅰ, Beclin-1, and P62 using Western blotting.</p><p><b>RESULTS</b>Compared with the control cells, the cells with H/R exhibited significantly increased expressions of pADPr, Bax and p-YH2ax ( < 0.05). The expressions of LC3B Ⅱ, beclin-1 and p62 were also increased significantly in the cells with H/R ( < 0.05), indicating the block of the autophagic flow. The application of PARP-1 inhibitor PJ34 in the cells with H/R significantly inhibited the expressions of pADPr ( < 0.05) and Bax ( < 0.01), and alleviated DNA damage in the cells. PJ34 treatment did not cause significant changes in the expressions of LC3B Ⅱ and beclin-1 but significantly decreased the expression of p62 ( < 0.05) in the cells with H/R.</p><p><b>CONCLUSIONS</b>Block of autophagic flow mediated by PARP-1 activation plays a role in myocardial ischemiareperfusion injury, and inhibition of PARP-1 activity can reverse autophagic flow block to reduce the injury.</p>