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, Kin Lam Ken YUNG, Ruijin LI

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1 Citation (Scopus)

Abstract

Fine particulate matter (PM2.5) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM2.5, and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM2.5-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 PM2.5. Results illustrated that PM2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM2.5 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 PM2.5 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 PM2.5 and that miR-421i and resveratrol exert protective effects against PM2.5-incurred cardiotoxicity. Copyright © 2023 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.

Original languageEnglish
Pages (from-to)288-300
JournalJournal of Environmental Sciences
Volume138
Early online dateMar 2023
DOIs
Publication statusPublished - Apr 2024

Citation

Chen, S., Chen, W., Li, Z., Yue, J., Yung, K. K. L., & Li, R. (2024). Regulation of PM2.5 on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol. Journal of Environmental Sciences, 138, 288-300. https://doi.org/10.1016/j.jes.2023.03.016

Keywords

  • Fine particulate matter
  • Rat H9c2 cells
  • Mitochondrial damage
  • MiR-421
  • SIRT3
  • Resveratrol

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