Abstract 311: Signal Transducer and Activator of Transcription 3 Inhibits the Opening of Mitochondrial Calcium Uniporter Against Cardiac Ischemia/reperfusion in Hydrogen Peroxide Postconditioning

• DOI: 10.1161/res.125.suppl_1.311
• Publication Date: 2019-10-16T17:53:59Z
• Authors: Lan Wu; Ji-liang Tan; Zhong-yan Chen; Gang Huang
• Keywords: Cardioprotection; Uniporter

Reactive oxygen species (ROS) generated during early reperfusion activated signal transducer and activator of transcription 3 (STAT3) contribute to intermittent hypobaric hypoxia (IHH)-afforded cardioprotection against ischemia/reperfusion (I/R)-induced mitochondrial calcium overload, but its mechanisms are not fully understood. This study investigated whether ROS signaling STAT3 is involved in moderate hydrogen peroxide postconditioning (H 2 O PoC) mimicked IHH cardiac I/R injury the possible downstream target mitochondria that mediates H PoC-afforded cardioprotection. Moderate PoC only improved post-ischemic recovery myocardial contractile performance reduce infarct size isolated rat hearts, also alleviated cytosolic Ca 2+ overload transients cell contraction cardiomyocytes. However, cardioprotective effects was abrogated by janus kinase (JAK2)/STAT3 inhibitor AG490 hearts as well adenovirus-delivered shRNAs specific for opener uniporter (MCU) spermine, respectively, adult cardiomyoctes with simulated I/R. Besides, spermine could be rescued overexpression Moreover, enhanced expression serine 727 phosphorylation Furthermore, immunofluorescence co-immunoprecipitation assay revealed a co-localization/interaction MCU at 5 min 30 cells. Co-immunoprecipitation further confirmed interacted N-terminal domain (NTD) PoC. These findings indicate alleviating through inhibiting opening via interaction NTD MCU. Our finds provide new insight into