NF-κB signaling is essential for resistance to heat stress-induced early stage apoptosis in human umbilical vein endothelial cells.
Cell apoptosis induced by heat stress is regulated by a complex signaling network. We previously reported that a p53-dependent pathway is involved. Here, we present evidence that NF-κB signaling plays a crucial role in preventing heat stress-induced early apoptosis. Human umbilical vein endothelial cells (HUVECs) were examined and increased phosphorylation of p65 and IκBα were detected, without IκBα degradation. When NF-κB signaling was inhibited by BAY11-7082, or a small interference RNA (siRNA) targeting p65, a significant increase in cell apoptosis and caspase-3 activity was observed, as well as reduced expression and translocation of HSP27 into the nucleus, an accumulation of reactive oxygen species, and prolonged phosphorylation of mitogen-activated protein kinases (MAPKs). In addition, an association between HSP27 and p65 was identified which may enhance NF-κB activation. When HSP27 was overexpressed, pretreatment of HUVECs with the antioxidant, apocynin, or N-acetyl cysteine, suppressed apoptosis. Similarly, inhibition of JNK and p38 with SP600125 and SB203580, respectively, also suppressed apoptosis, whereas siRNA-mediated HSP27 knockdown and treatment with the ERK 1/2 inhibitor PD98059 did otherwise. In conclusion, these findings suggest a novel role for an NF-κB signaling pathway involving HSP27, ROS, and MAPKs that confers a protective effect against heat stress-induced cell apoptosis.
Southern Medical University, Guangzhou, China.
Yanan
Y
Liu
Guangzhou University of Chinese Medicine, Guangzhou, China.
Gengbiao
G
Zhou
Guangzhou University of Chinese Medicine, Guangzhou, China.
Zhenglian
Z
Wang
Department of Pathophysiology, Southern Medical University, Guangzhou, China.
Xiaohua
X
Guo
Department of ICU, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, China.|Postdoctoral Workstation, Huabo Bio-pharmaceutical Research Institute, Guangzhou, China.
Qiulin
Q
Xu
Department of Pathophysiology, Southern Medical University, Guangzhou, China.
Qiaobing
Q
Huang
Southern Medical University, Guangzhou, China.|Department of ICU, General Hospital of Guangzhou Military Command, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, China.
Lei
L
Su
D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology*
D006360:Heat-Shock Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species