Regulation of PM2.5 on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol

Shanshan Chen; Wenqi Chen; Zhiping Li; Jianwei Yue; Ken Kin Lam Yung; Ruijin Li

doi:10.1016/j.jes.2023.03.016

Regulation of PM_2.5 on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol

J Environ Sci (China). 2024 Apr:138:288-300. doi: 10.1016/j.jes.2023.03.016. Epub 2023 Mar 21.

Authors

Shanshan Chen¹, Wenqi Chen¹, Zhiping Li², Jianwei Yue², Ken Kin Lam Yung³, Ruijin Li⁴

Affiliations

¹ Institute of Environmental Science, Shanxi University, Taiyuan 030006, China.
² Institute of Judicial Identification Techniques for Environmental Damage, Shanxi University and Shanxi Unisdom Testing Technology Co., Ltd., Taiyuan 030006, China.
³ Institute of Environmental Science, Shanxi University, Taiyuan 030006, China; Department of Biology, Hong Kong Baptist University, Hong Kong, China. Electronic address: kklyung@hkbu.edu.hk.
⁴ Institute of Environmental Science, Shanxi University, Taiyuan 030006, China; Institute of Judicial Identification Techniques for Environmental Damage, Shanxi University and Shanxi Unisdom Testing Technology Co., Ltd., Taiyuan 030006, China; Shanxi Yellow River Laboratory, Taiyuan 030006, China. Electronic address: lirj@sxu.edu.cn.

PMID: 38135396
DOI: 10.1016/j.jes.2023.03.016

Abstract

Fine particulate matter (PM_2.5) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM_2.5, and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM_2.5-triggered mitochondrial injury of cardiomyocytes is unclear. This study focused on the miR-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM_2.5. Results illustrated that PM_2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM_2.5 up-regulated miR-421 and down-regulated SIRT3 gene expression, along with decreasing p-FOXO3a (SIRT3 downstream target gene) and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1. Further, miR-421 inhibitor (miR-421i) and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM_2.5 exposure and mediated the expression of SOD2, OPA1 and Drp1, restoring the mitochondrial morphology and function. It suggests that miR-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM_2.5 and that miR-421i and resveratrol exert protective effects against PM_2.5-incurred cardiotoxicity.

Keywords: Fine particulate matter; MiR-421; Mitochondrial damage; Rat H9c2 cells; Resveratrol; SIRT3.

MeSH terms

Animals
Cardiovascular Diseases*
MicroRNAs*
Particulate Matter / toxicity
Rats
Resveratrol
Sirtuin 3* / genetics
Sirtuin 3* / metabolism

Substances

Sirtuin 3
Resveratrol
Particulate Matter
MicroRNAs