NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells
In: Molecular Medicine Reports, Jg. 24 (2021-09-22)
Online
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Zugriff:
The results of a previous study demonstrated that heat stress (HS) triggered oxidative stress, which in turn induced the apoptosis of epithelial cells. These results uncovered a novel mechanism underlying the activation of NF-κB in primary human umbilical vein endothelial cells. The present study aimed to further investigate the role of NF-κB/IκBα signaling pathways in the inhibition of HS-induced reactive oxygen species (ROS) generation and cytotoxicity in endothelial cells. The results of the present study demonstrated that HS triggered a significant amount of NF-κB and IκBα nuclear translocation without IκBα degradation in a time-dependent manner. Mutant constructs of IκBα phosphorylation sites (Ser32, Ser36) were employed in rat pulmonary microvascular endothelial cells (PMVECs). Cell Counting Kit-8 assays demonstrated that both the small interfering (si)RNA-mediated knockdown of p65 and IκBα mutant constructs significantly decreased cell viability and aggravated ROS accumulation in HS-induced rat PMVECs compared with the control. Additionally, western blot analysis revealed that p65 siRNA attenuated the protein expression of IκBα. However, IκBα mutant constructs failed to attenuate NF-κB activation and nuclear translocation, indicating that IκBα-independent pathways contributed to NF-κB activity and nucleus translocation in a time-dependent manner following HS. Collectively, the results of the present study suggested that the NF-κB/IκBα pathway was essential for resistance to HS-induced ROS production and cytotoxicity in rat PMVECs, and that it could be a potential therapeutic target to reduce the mortality and morbidity of heat stroke.
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NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells
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Autor/in / Beteiligte Person: | Fu, Weijun ; Chen, Hui ; Liu, Yanan ; Xie, Weidang ; Huang, Wei ; Cai, Shumin ; Chen, Zhongqing |
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Zeitschrift: | Molecular Medicine Reports, Jg. 24 (2021-09-22) |
Veröffentlichung: | Spandidos Publications, 2021 |
Medientyp: | unknown |
ISSN: | 1791-3004 (print) ; 1791-2997 (print) |
DOI: | 10.3892/mmr.2021.12454 |
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