title: Heat stress pretreatment decreases lipopolysaccharide-induced apoptosis via the p38 signaling pathway in human umbilical vein endothelial cells.
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.
authors.affiliation: Department of Intensive Care Unit, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Intensive Care Unit, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Critical Illness Research Centre, Lawson Health Research Institute, University of Western Ontario, London, ON N6A 4G5, Canada.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Critical Illness Research Centre, Lawson Health Research Institute, University of Western Ontario, London, ON N6A 4G5, Canada.
authors.forename: Inga
authors.initials: I
authors.lastname: Cepinskas
authors.affiliation: Critical Illness Research Centre, Lawson Health Research Institute, University of Western Ontario, London, ON N6A 4G5, Canada.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Peng
authors.affiliation: Department of Intensive Care Unit, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Su
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation; D015870:Gene Expression; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D006358:Hot Temperature; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D055551:HSP27 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3