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Updated: Jun 7, 2025

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

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TSPO exacerbates sepsis-induced cardiac dysfunction by inhibiting p62-Mediated autophagic flux via the

Qiao Guo1, Haitang Liao2, Shuai Hao3

  • 1Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.

Free Radical Biology & Medicine
|November 14, 2024
PubMed

Insights

Translocator protein (TSPO) exacerbates septic cardiomyopathy by impairing mitochondrial function and autophagy. Targeting TSPO with NADH shows promise for treating sepsis-induced cardiac injury.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pathophysiology

Background:

  • Septic cardiomyopathy (SCM) is a severe sepsis complication linked to mitochondrial dysfunction and disrupted autophagic flux.
  • Translocator protein (TSPO) is implicated in SCM pathogenesis, but its precise role and therapeutic potential remain unclear.

Purpose of the Study:

  • To investigate the role of TSPO in SCM development.
  • To evaluate TSPO as a therapeutic target for sepsis-induced cardiac injury.

Main Methods:

  • TSPO expression was measured in sepsis patients, septic rats, and LPS-stimulated cardiomyocytes.
  • Mitochondrial function, reactive oxygen species (ROS) production, and the RIP1/RIP3 pathway were assessed.
  • The effect of NADH on TSPO-related pathways and cardiac function was evaluated in septic rats.

Main Results:

  • Increased TSPO expression was observed in sepsis patients and animal models.
  • Elevated TSPO disrupted mitochondrial function, increased ROS, activated RIP1/RIP3, and impaired autophagosome degradation.
  • NADH binding to TSPO restored autophagic flux, improved mitochondrial function, and enhanced cardiac performance and survival in septic rats.

Conclusions:

  • TSPO plays a critical role in SCM pathogenesis by exacerbating mitochondrial dysfunction and inflammation.
  • Targeting TSPO with NADH represents a potential therapeutic strategy to mitigate sepsis-induced cardiac injury.
Keywords:
Autophagy fluxCardiomyopathyExosomesInflammationLC3II/IRIP 1/RIP 3Reactive oxygen species (ROS)SepsisTSPOp62

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