Manganese Mitigates Heat Stress-Induced Apoptosis by Alleviating Endoplasmic Reticulum Stress and Activating the NRF2/SOD2 Pathway in Primary Chick Embryonic Myocardial Cells

Heat stress leads to oxidative stress and induces apoptosis in various cells. Endoplasmic reticulum (ER) stress is an important apoptosis pathway. Manganese (Mn) has been shown to enhance the activity of manganese superoxide dismutase (MnSOD). To explore the potential effect of Mn on ER stress and apoptosis induced by heat stress, we examined crucial factors associated with heat stress, ER stress, and apoptosis in cultured primary chick embryonic myocardial cells that had been pretreated with 20 mu M Mn for 24 h and then subjected to 4 h of heat stress. The results showed that Mn decreased (P < 0.05) heat stress-induced reactive oxygen species (ROS) production and exerted antiapoptotic effects by increasing MnSOD enzymatic activity. The heat stress-induced accumulation of intracellular calcium was dramatically reduced (P < 0.05). Mn treatment significantly decreased (P < 0.05) the expression levels of the apoptosis-related gene Bax and ER stress markers glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in primary chick embryonic myocardial cells. Additionally, Mn reduced oxidative stress by activating the nuclear factor E2-related factor 2 (NRF2)/SOD2 signaling pathway. Taken together, our findings indicate that Mn attenuates heat stress-induced apoptosis by inhibiting ROS generation, intracellular calcium accumulation, and the ER stress pathway and activating the NRF2/SOD2 signaling pathway to protect myocardial cells from oxidative stress during chick embryonic development.

Automated summary

The study found that manganese (Mn) can reduce oxidative stress induced by heat stress and exert antiapoptotic effects by increasing MnSOD enzymatic activity. Additionally, Mn can lower oxidative stress levels by activating the nuclear factor E2-related factor 2 (NRF2)/SOD2 signaling pathway, thereby protecting myocardial cells during embryonic development.