Heat stress suppresses MnSOD expression via p53-Sp1 interaction and induces oxidative stress damage in endothelial cells: Protective effects of MitoQ10 and Pifithrin-α

Autor: Jian Gong, Peipei Sun, Li Li, Zhimin Zou, Qihua Wu, Liyun Sun, Hui Li, Zhengtao Gu, Lei Su
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Heliyon, Vol 9, Iss 12, Pp e22805- (2023)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2023.e22805
Popis: Aim: To investigate the mechanism of p53-mediated suppression of heat stress-induced oxidative stress damage by manganese superoxide dismutase (MnSOD) in endothelial cells (ECs). Methods: Primary ECs isolated from mouse aortas were used to examine the effects of heat stress on vascular ECs viability and apoptosis. We measured MnSOD expression, reactive oxygen species (ROS) production, p53 expression, viability, and apoptosis of heat stress-induced ECs. We also tested the protective effects of MitoQ10, a mitochondrial-targeted antioxidant, and Pifithrin-α, a p53 inhibitor, in ECs from a mouse model of heat stroke. Results: Heat stress increased cellular apoptosis, ROS production, and p53 expression, while reducing cellular viability and MnSOD expression in ECs. We also showed that the suppression of MnSOD expression by heat stress in ECs was mediated by interactions between p53 and Sp1. Furthermore, MitoQ10 and Pifithrin-α alleviated heat stress-induced oxidative stress and apoptosis in ECs. Conclusion: Our results revealed that p53-mediated MnSOD downregulation is a key mechanism for heat stress-induced oxidative stress damage in ECs and indicated that MitoQ10 and Pifithrin-α could be potential therapeutic agents for heat stroke.
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