Y‐box protein 1 promotes hypoxia/reoxygenation‐ or ischemia/reperfusion‐induced cardiomyocyte apoptosis via SHP‐1‐dependent STAT3 inactivation

Abstract Cardiomyocyte apoptosis induced by hypoxia and ischemia plays important roles in heart dysfunction after acute myocardial infarction (AMI). However, the mechanism of apoptosis induction remains unclear. A previous study reported that Y‐box protein 1 (YB1) is upregulated after myocardial hypoxia/reoxygenation or ischemia/reperfusion (H/R or I/R, respectively) injury; however, whether YB1 is associated with H/R‐induced cardiomyocyte apoptosis is completely unknown. In the present study, we investigated the roles of YB1 in H/R‐induced cardiomyocyte apoptosis and the possible underlying molecular mechanisms. In vitro, H/R treatment upregulated the YB1 expression in H9C2 cells, whereas YB1 knockdown inhibited H/R‐induced cardiomyocyte apoptosis and induced H9C2 cell proliferation via Src homology region 2 domain‐containing phosphatase 1 (SHP‐1)‐mediated activation of signal transducer and activator of transcription 3 (STAT3). In vivo, YB1 knockdown ameliorated AMI, reducing infarct size, cardiomyocyte apoptosis, and oxidative stress, via SHP‐1‐mediated inactivation of STAT3. Additionally, YB1 knockdown inhibited H/R‐ or I/R‐induced oxidative stress in vitro and in vivo. H/R and I/R increase YB1 expression, and YB1 knockdown ameliorates AMI injury via SHP‐1‐dependent STAT3 inactivation.