title: Protection against endotoxemia by HSP70 in rodent cardiomyocytes.
abstract: Clinical and experimental studies have shown that myocardial dysfunction is an early event during endotoxemia or septic shock. Several reports have shown that rodents submitted to a mild heat shock become resistant to lipopolysaccharides (LPS) or sepsis. The most abundant of the heat shock proteins (HSP), the HSP70, has been postulated to be the principal mediator of the observed protection against endotoxemia. We have tested the hypothesis that a protective effect against endotoxemia is achievable by the increased presence of the HSP70 in rodent cardiomyocytes. We have found that a transgenic mouse line overexpressing the rat HSP70 gene in the heart exhibits an increased tolerance to LPS treatment (control estimated survival function [S(t)] = 0.538, transgenic S(t) = 0.787, P < 0.05). Interestingly, the increased presence of the HSP70 in the hearts of these mice results in a decrease in the activation of the inducible nitric oxide synthase (iNOS) after LPS treatment. We conclude that HSP70 protection against LPS is most probably mediated through the modulation of iNOS activation and the subsequent decreased synthesis of nitric oxide in cardiomyocytes.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0618, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Lau
authors.forename: T M
authors.initials: TM
authors.lastname: Griffin
authors.forename: R
authors.initials: R
authors.lastname: Mestril
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D018869:Heat-Shock Response / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015996:Survival Rate
chemical_list: D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002956:Citrulline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003402:Creatine Kinase