1. Academic Validation
  2. Serinc2 deficiency exacerbates sepsis-induced cardiomyopathy by enhancing necroptosis and apoptosis

Serinc2 deficiency exacerbates sepsis-induced cardiomyopathy by enhancing necroptosis and apoptosis

  • Biochem Pharmacol. 2023 Oct 31:115903. doi: 10.1016/j.bcp.2023.115903.
Shan Hu 1 Min Huang 1 Shuai Mao 1 Manqi Yang 1 Hao Ju 1 Zheyu Liu 1 Mian Cheng 2 Gang Wu 3
Affiliations

Affiliations

  • 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Department of Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Department of Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
  • 2 Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, PR China. Electronic address: cheng.mian@icloud.com.
  • 3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Department of Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Department of Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China. Electronic address: gangwu@whu.edu.cn.
Abstract

In critical care medicine, sepsis is a potentially fatal syndrome characterized by multi-organ dysfunction and eventual failure. Sepsis-induced cardiomyopathy (SIC) is characterized by decreased venstricular contractility. Serine incorporator 2 (Serinc2) is a protein involved in phosphatidylserine biosynthesis and membrane incorporation. It may also be a protective factor in septic lung injury. However, it is unknown whether Serinc2 influences SIC onset or progression. In the present study, we found that Serinc2 was downregulated in the cardiomyocytes of cecal ligation and puncture (CLP)-induced SIC and in neonatal rat cardiomyocytes (NRCMs) exposed to lipopolysaccharides (LPS). Serinc2 knockout (KO) exacerbated sepsis-induced myocardial inflammation, Necroptosis, Apoptosis, myocardial damage, and contractility impairment. Furthermore, the lack of Serinc2 in cardiomyocytes aggravated LPS-induced cardiomyopathic inflammation, Necroptosis, and Apoptosis. An adenovirus overexpressing Serinc2 inhibited the inflammatory response and favored cardiomyocyte survival. A mechanistic analysis revealed that Serinc2 deficiency exacerbated LPS-induced cardiac dysfunction by inhibiting the protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK-3β) signaling pathway that regulates necrotic complex formation and apoptotic pathways in cardiomyopathy. The findings of the present work demonstrated that Serinc2 plays an essential role in SIC and is, therefore, promising as a prophylactic and therapeutic target for this condition.

Keywords

Apoptosis; Cardiac dysfunction; Necroptosis; Sepsis; Serinc2.

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