FAM134B-mediated endoplasmic reticulum autophagy protects against sepsis myocardial injury in mice.

Abstract

Reticulophagy regulator 1 (RETEG1, also known as FAM134B) plays a crucial role in endoplasmic reticulum autophagy. We aimed to explore the effect of FAM134B-mediated endoplasmic reticulum autophagy in sepsis myocardial injury in mice. Sepsis myocardial injury mice were established via cecal ligation and puncture procedures. The expression of FAM134B and LC3-II/I was determined using immunohistochemistry. Myocardial tissue morphological changes and apoptosis were examined using hematoxylin and eosin (H&E) staining and TUNEL analysis. The effects of FAM134B knockdown or overexpression on mice with sepsis myocardial injury were also studied. The levels of TNF-α, IL-6, IL-8, and IL-10 were evaluated using enzyme-linked immunosorbent assay (ELISA). Autophagy- and apoptosis-related protein expression was detected using western blotting. The effect of FAM134B on Lipopolysaccharide (LPS) -induced cardiomyocytes was also studied. The expression of FAM134B and LC3-II/I increased in sepsis mice and lipopolysaccharide (LPS)-treated cardiomyocytes. 3-Methyladenine (3-MA) significantly inhibited FAM134B and LC3-II/I expression and promoted myocardial injury, inflammation response, and cardiomyocyte apoptosis. The overexpression of FAM134B could minimize myocardial injury, inflammation, and apoptosis, whereas FAM134B knockdown showed opposite effects. FAM134B-mediated endoplasmic reticulum autophagy had a protective effect on sepsis myocardial injury in mice by reducing inflammation and tissue apoptosis, which may provide new insights for sepsis myocardial injury therapies.

• Authors: Tong Li, Yongsheng Chen, Yue Li, Zhipeng Yao, Wenhua Liu
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 10 Pg. 13535-13547 (03 26 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 33819192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autophagy-Related Proteins
• Cardiotonic Agents
• Fam134b protein, mouse
• Lipopolysaccharides
• Membrane Proteins
• RNA, Messenger

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects, genetics)
• Autophagy-Related Proteins (genetics, metabolism)
• Cardiotonic Agents (metabolism)
• Endoplasmic Reticulum (drug effects, metabolism)
• Gene Expression Regulation (drug effects)
• Inflammation (pathology)
• Lipopolysaccharides
• Male
• Membrane Proteins (genetics, metabolism)
• Mice, Inbred C57BL
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism)
• RNA, Messenger (genetics, metabolism)
• Sepsis (genetics, pathology)