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

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Abstract

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 μM 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.

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The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

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Funding

This research was funded by National Natural Science Foundation of China (No. 03119023); Youth Science and Technology Fund Scheme in Gansu (No. 20JR5RA013); Special Funds for Talents of Gansu Agricultural University (No. 2017RCZX-18).

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Authors and Affiliations

  1. College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, Gansu, 730070, People’s Republic of China

    Shizhen Qin, Rui Wang, Defu Tang, Yanli Guo & Zhaoguo Shi

  2. General Station of Agricultural Technology Extension in Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China

    Shijiao Qin

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  1. Shizhen Qin
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  2. Rui Wang
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  3. Defu Tang
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  4. Shijiao Qin
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  5. Yanli Guo
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  6. Zhaoguo Shi
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Contributions

Conceptualization, Shizhen Qin; investigation, Rui Wang; writing – original draft, Rui Wang and Shijiao Qin; writing – review and editing, Yanli Guo; supervision, Defu Tang; project administration, Zhaoguo Shi; funding acquisition, Shizhen Qin.

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Correspondence to Zhaoguo Shi.

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Qin, S., Wang, R., Tang, D. et al. Manganese Mitigates Heat Stress–Induced Apoptosis by Alleviating Endoplasmic Reticulum Stress and Activating the NRF2/SOD2 Pathway in Primary Chick Embryonic Myocardial Cells. Biol Trace Elem Res 200, 2312–2320 (2022). https://doi.org/10.1007/s12011-021-02810-2

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