Heat stress pretreatment decreases lipopolysaccharide-induced apoptosis via the p38 signaling pathway in human umbilical vein endothelial cells

Liu,Zhifeng; Zhong,Tianyu; Zheng,Dong; Cepinskas,Inga; Peng,Tianqing; Su,Lei

doi:10.3892/mmr.2016.5303

Heat stress pretreatment decreases lipopolysaccharide-induced apoptosis via the p38 signaling pathway in human umbilical vein endothelial cells

Authors:
- Zhifeng Liu
- Tianyu Zhong
- Dong Zheng
- Inga Cepinskas
- Tianqing Peng
- Lei Su
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Affiliations: Department of Intensive Care Unit, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China, Critical Illness Research Centre, Lawson Health Research Institute, University of Western Ontario, London, ON N6A 4G5, Canada
Published online on: May 18, 2016 https://doi.org/10.3892/mmr.2016.5303
Pages: 1007-1013

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Abstract

The present study aimed to investigate vascular endothelial apoptosis, and the regulatory molecules involved in the condition of heatstroke caused by direct hyperthermia due to high core temperature and gut‑derived endotoxemia. Human umbilical vascular endothelial cells (HUVECs) were isolated and treated with heat stress (43˚C for 1 h), lipopolysaccharide (LPS; 1 µg/ml), or a combination of heat stress pretreatment followed by LPS. Caspase‑3 activity, DNA fragmentation, and cell viability, determined using a 3‑(4, 5‑dimethyl thiazol‑2‑yl)‑2,5‑diphenyl tetrazolium bromide assay, were measured to examine cellular apoptosis. Changes in the expression levels of heat shock protein (HSP) 27, HSP90 and B‑cell lymphoma 2 (Bcl‑2), and the phosphorylation of p38 were detected using Western blot assays. The specific inhibitor of p38, SB203580, was also used. LPS induced endothelial apoptosis, as indicated by increased caspase‑3 activity, a high level of DNA fragmentation and low cell viability. LPS also increased p38 phosphorylation and decreased the expression levels of HSP27, HSP90 and Bcl‑2. Heat stress pretreatment inhibited LPS‑induced cellular apoptosis, increased the phosphorylation of p38, and increased the expression levels of HSP27, HSP90 and Bcl‑2. Pretreatment with SB203580 had effects similar to those of heat stress in the amelioration of LPS‑induced effects. These findings demonstrated that heat stress pretreatment decreased LPS‑induced Bcl‑2‑associated apoptosis in HUVECs by attenuating p38 activation, thereby increasing the expression levels of HSP27 and HSP90.

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