Sirt3-Bnip3 signaling axis alleviates myocardial ischemia/reperfusion-induced cardiac injury via regulating GSDME
Yin Z, Jia X, Zhang B, Gong Y, Zheng Q, Lu L (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 138
Article Number: 112202
DOI: 10.1016/j.cellsig.2025.112202
Abstract
Myocardial ischemia/reperfusion (MI/R) injury is a serious complication of myocardial infarction, resulting in acute cardiac dysfunction, arrhythmias, and potentially sudden death. However, the exact mechanisms of MI/R remain unclear. Mitochondrial dysfunction, mediated by mitophagy imbalance, is an important molecular mechanism leading to cardiac dysfunction post-MI/R. The study aims to investigate the roles of the Sirt3-Bnip3 axis and GSDME during MI/R injury. We established MI/R and simulated ischemia/reperfusion (SIR) injury models using male C57BL/6 J mice and H9c2 cells respectively. To regulate the expression of Sirt3, Bnip3 and GSDME, we used adenovirus, activators, inhibitors and small interfering RNA (siRNA). Echocardiography was utilized to assess cardiac function. Western blot was used to determine the levels of protein expression. Our data revealed that Sirt3 and Bnip3 were down regulated after MI/R injury stress. Increasing Sirt3 and Bnip3 expression levels resulted in a reduction of myocardial infarct, apoptosis rate, reactive oxygen species (ROS) production, serum lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels. Further studies revealed that the Sirt3-Bnip3 signaling axis mitigates MI/R injury by inhibiting the activity of the key pyroptosis signal molecule GSDME. The discovery offers a promising target for the treatment of MI/R injury.
Authors with CRIS profile
Involved external institutions
Second Affiliated Hospital of Zhejiang University (SAHZU) / 浙江大学 医学院 附属第二医院
China (CN)
Xijing Hospital / 西京医院
China (CN)
China (CN)
Xijing Hospital / 西京医院
China (CN)
How to cite
APA:
Yin, Z., Jia, X., Zhang, B., Gong, Y., Zheng, Q., & Lu, L. (2026). Sirt3-Bnip3 signaling axis alleviates myocardial ischemia/reperfusion-induced cardiac injury via regulating GSDME. Cellular Signalling, 138. https://doi.org/10.1016/j.cellsig.2025.112202
MLA:
Yin, Zhiqiang, et al. "Sirt3-Bnip3 signaling axis alleviates myocardial ischemia/reperfusion-induced cardiac injury via regulating GSDME." Cellular Signalling 138 (2026).
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