1. Academic Validation
  2. Endoplasmic reticulum stress mediated by ROS participates in cadmium exposure-induced MC3T3-E1 cell apoptosis

Endoplasmic reticulum stress mediated by ROS participates in cadmium exposure-induced MC3T3-E1 cell apoptosis

  • Ecotoxicol Environ Saf. 2023 Feb;251:114517. doi: 10.1016/j.ecoenv.2023.114517.
Lina Jia 1 Tianwen Ma 1 Liangyu Lv 1 Yue Yu 1 Mingchao Zhao 1 Hong Chen 1 Li Gao 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin, China; Heilongjiang Key Laboratory of Animals Disease Pathogenesis and Comparative Medicine, Harbin, China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin, China; Heilongjiang Key Laboratory of Animals Disease Pathogenesis and Comparative Medicine, Harbin, China. Electronic address: gaoli43450@163.com.
Abstract

Cadmium (Cd), as one of the seventh most toxic heavy metal pollutants, widely persisted in the environment, leading to osteoblast dysfunction and ultimately Cd-related skeletal disease. However, the damaging effects of Cd on cellular functions and the potential pathogenic mechanisms are still unclear. In our study, Cd is believed to induce mitochondrial dysfunction and endoplasmic reticulum stress (ERS) in a dose-dependent manner, thereby leading to Apoptosis, as evident by elevated Drp1, Fis1, GRP78, CHOP, ATF4, P-EIF2α, P-PERK, Bax, cleaved Caspase 3 proteins expression and ROS levels, and decreased the levels of Mfn2, OPA1, Bcl2, and intracellular Collagen I, B-ALP, RUNX2, and BGP genes. Additionally, when the exogenous addition of NAC and 4-PBA was added, it was found that NAC and 4-PBA had a positive moderating effect on Cd-induced cell dysfunction. Mechanistically, Cd-induced oxidative stress and Apoptosis by upregulating the PERK-EIF2α-ATF4-CHOP signaling pathway and inhibiting the Nrf2/NQO1 pathway. In conclusion, we found that Cd was involved in mitochondrial dysfunction, ERS, and Apoptosis in MC3T3-E1 cells, While NAC and 4-PBA relieved ERS and attenuated cell Apoptosis.

Keywords

Apoptosis; Cadmium; ERS; Osteoporosis; Oxidative damage.

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