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- Title
ANXA1sp modulates the protective effect of Sirt3‐induced mitophagy against sepsis‐induced myocardial injury in mice.
- Authors
Ma, Wanyu; Huang, Zhijia; Miao, Yanmei; Ma, Xinglong; Zhang, Zhiquan; Liu, Wenjie; Xie, Peng
- Abstract
Aim: Sepsis‐induced myocardial injury (SIMI) may be associated with insufficient mitophagy in cardiomyocytes, but the exact mechanism involved remains unknown. Sirtuin 3 (Sirt3) is mainly found in the mitochondrial matrix and is involved in repairing mitochondrial function through means such as the activation of autophagy. Previously, we demonstrated that the annexin‐A1 small peptide (ANXA1sp) can promote Sirt3 expression in mitochondria. In this study, we hypothesized that the activation of Sirt3 by ANXA1sp induces mitophagy, thereby providing a protective effect against SIMI in mice. Methods: A mouse model of SIMI was established via cecal ligation and puncture. Intraperitoneal injections of ANXA1sp, 3TYP, and 3MA were administered prior to modeling. After successful modeling, IL‐6, TNF‐α, CK‐MB, and CTn‐I levels were measured; cardiac function was assessed using echocardiography; myocardial mitochondrial membrane potential, ROS, and ATP production were determined; myocardial mitochondrial ultrastructure was observed using transmission electron microscopy; and the expression levels of Sirt3 and autophagy‐related proteins were detected using western blotting. Results: ANXA1sp significantly reduced serum IL‐6, TNF‐α, CK‐MB, and CTn‐I levels; decreased myocardial ROS production; increased mitochondrial membrane potential and ATP synthesis; and improved myocardial mitochondrial ultrastructure in septic mice. Furthermore, ANXA1sp promoted Sirt3 expression and activated the AMPK‐mTOR pathway to induce myocardial mitophagy. These protective effects of ANXA1sp were reversed upon treatment with the Sirt3 blocker, 3‐TYP. Conclusion: ANXA1sp can reverse SIMI, and the underlying mechanism may be related to the activation of the AMPK‐mTOR pathway following upregulation of Sirt3 by ANXA1sp, which, in turn, induces autophagy.
- Subjects
MYOCARDIAL injury; MEMBRANE potential; MITOCHONDRIAL membranes; TRANSMISSION electron microscopy; PEPTIDES
- Publication
Acta Physiologica, 2024, Vol 240, Issue 8, p1
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/apha.14184