1. YB1 protects cardiac myocytes against H2O2-induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3
- Author
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Fuwei He, Zhenwei Li, Shiqi Wang, Yewen Hu, Xiaomin Chen, and Ning Huangfu
- Subjects
0301 basic medicine ,Male ,STAT3 Transcription Factor ,Cancer Research ,Small interfering RNA ,p38 mitogen-activated protein kinases ,PIAS3 ,Apoptosis ,Myocardial Reperfusion Injury ,Protective Agents ,Biochemistry ,Cell Line ,STAT3 ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,oxidative stress ,Animals ,Protein inhibitor of activated STAT ,Myocytes, Cardiac ,STAT1 ,RNA, Messenger ,Phosphorylation ,RNA, Small Interfering ,Promoter Regions, Genetic ,Molecular Biology ,Gene knockdown ,Messenger RNA ,biology ,M-I/R ,Chemistry ,Myocardium ,Articles ,Hydrogen Peroxide ,Protein Inhibitors of Activated STAT ,Cell biology ,Rats ,030104 developmental biology ,Oncology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,STAT protein ,biology.protein ,Molecular Medicine ,YB1 ,Y-Box-Binding Protein 1 ,Molecular Chaperones - Abstract
Oxidative stress serves important roles in cardiac injury during the process of ischemia/reperfusion (I/R). Y‑box protein 1 (YB1), a member of the highly conserved Y‑box protein family, is closely associated with inflammation and stress responses by regulating gene transcription, RNA splicing and mRNA translation. However, the roles of YB1 in oxidative stress‑induced myocardial‑I/R (M‑I/R) injury are unknown. The aim of the present study was to examine the effects of YB1 on H2O2‑induced cardiomyocyte injury and its underlying mechanism. The results demonstrated that YB1 expression was upregulated during H2O2‑induced myocardial injury. YB1 knockdown through transfection of small interfering RNA significantly aggravated cardiac cell apoptosis. Furthermore, YB1 knockdown significantly reversed the H2O2‑mediated increase in phosphorylated signal transducer and activator of transcription (STAT)3, but did not affect the phosphorylation of P38, extracellular signal‑regulated kinases 1/2, c‑Jun N‑terminal kinases, P65, Janus kinase 1 and 2 or STAT1. Moreover, protein co‑immunoprecipitation and RNA‑binding protein immunoprecipitation assays revealed that YB1 interacted with protein inhibitor of activated STAT 3 (PIAS3) mRNA but not its translated protein. YB1 overexpression may have promoted PIAS3 mRNA decay, decreasing PIAS3 protein levels, and therefore increased the levels of phosphorylated STAT3. Finally, YB1 knockdown, mediated by a lentivirus carrying YB1 targeted short hairpin RNA, significantly decreased left ventricle percentage fractional shortening and ejection fraction values, while increasing the infarct sizes in a rat model of M‑I/R injury. These results demonstrated for the first time (to the best of our knowledge) that YB1 may protect cardiac myocytes against H2O2 or M‑I/R‑induced injury by binding to PIAS3 mRNA and resulting in the phosphorylation of STAT3.
- Published
- 2019