Palmitic acid suppresses autophagy in neonatal rat cardiomyocytes via the cGAS-STING-IRF3 pathway.
10.12122/j.issn.1673-4254.2022.01.04
- Author:
Hui Lin YU
1
;
Qian LIU
1
;
Yong Zheng GUO
1
;
Yong XIA
1
;
Su Xin LUO
1
Author Information
1. Department of Cardiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
- Publication Type:Journal Article
- Keywords:
autophagy;
cGAS-STING-IRF3;
cardiomyocytes;
palmitic acid
- MeSH:
Animals;
Animals, Newborn;
Autophagy;
Myocytes, Cardiac;
Nucleotidyltransferases/pharmacology*;
Palmitic Acid/pharmacology*;
Rats
- From:
Journal of Southern Medical University
2022;42(1):36-44
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of palmitic acid (PA) on autophagy in neonatal rat cardiomyocytes (NRCMs) and explore the underlying mechanism.
METHODS:NRCMs were isolated and cultured for 24 h before exposure to 10% BSA and 0.1, 0.3, 0.5, or 0.7 mmol/L PA for 24 h. After the treatments, the expressions of Parkin, PINK1, p62, LC3Ⅱ/ LC3Ⅰ, cGAS, STING and p-IRF3/IRF3 were detected using Western blotting and the cell viability was assessed with CCK8 assay, based on which 0.7 mmol/L was selected as the optimal concentration in subsequent experiments. The effects of cGAS knockdown mediated by cGAS siRNA in the presence of PA on autophagy-related proteins in the NRCMs were determined using Western blotting, and the expressions of P62 and LC3 in the treated cells were examined using immunofluorescence assay.
RESULTS:PA at different concentrations significantly lowered the expressions of Parkin, PINK1, LC3 Ⅱ/LC3 Ⅰ and LC3 Ⅱ/LC3 Ⅰ+Ⅱ (P < 0.05), increased the expression of p62 (P < 0.05), and inhibited the viability of NRCMs (P < 0.05). Knockdown of cGAS obviously blocked the autophagy-suppressing effect of PA and improved the viability of NRCMs (P < 0.05).
CONCLUSION:PA inhibits autophagy by activating the cGAS-STING-IRF3 pathway to reduce the viability of NRCMs.
