E3 Ubiquitin Ligase FBXO32 Promotes Sepsis-Induced Cardiomyopathy by Regulating ANXA1/PI3K/AKT Signaling
Author:
Chen De1, Liang Xuan2, Zhang Lei2, Zhang Jingjing2, Gao Lina1, Yan Dong1, Zuo Kun2, Guo Hong2, Du Song2, Liu Jian1
Affiliation:
1. The First Clinical Medical College of Lanzhou University 2. Gansu Provincial Maternity and Child-care Hospital, Gansu Provincial Central Hospital
Abstract
Abstract
Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis. Therefore, understanding SIC pathogenesis and developing new therapeutic targets are of great significance. This study investigated the role of F-box-only protein 32 (FBXO32) in SIC pathogenesis. SIC models were established in rats and H9c2 cells using lipopolysaccharide. The effects of FBXO32 on myocardial apoptosis and mitochondrial structure and function were determined using electron microscopy, reactive oxygen species detection, and JC-1 staining. The molecular mechanism was elucidated using western blotting and co-immunoprecipitation. The results showed elevated FBXO32 expression in both in vivo and in vitro SIC models. FBXO32 knockdown alleviated apoptosis and mitochondrial and cardiac dysfunction. Mechanistic analysis revealed that FBXO32 promoted ubiquitination and degradation of annexin A1 (ANXA1), inhibiting the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) pathways. Rescue experiments demonstrated that ANXA1 knockdown reversed the effects of FBXO32 knockdown. This study suggests that FBXO32 exacerbates SIC progression by mediating ANXA1 ubiquitination and inhibiting the PI3K/AKT signaling pathway.
Publisher
Springer Science and Business Media LLC
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