Role of p38 mitogen-activated protein kinase pathway on heart failure in the infant rat after burn injury.
We examined the hypothesis that post-burn activation of the p38 mitogen-activated protein kinase (MAPK) pathway is one aspect of the signalling cascade culminating in post-burn secretion of tumour necrosis factor (TNF)-alpha which contributes to post-burn myocardial apoptosis. Studies were designed to determine the time course of the induction of p38MAPK, TNF-alpha and myocardial apoptosis after burn injury. Our quantitative bacterial culture data demonstrated that viable bacteria reached the heart, and Western blotting data identified the increase in the phosphorylation of p38MAPK at an early time after burn. The peak incidence of myocardial apoptosis was also seen at an early time after burn. The expression of TNF-alpha mRNA, infiltrated neutrophils and serum creatine phosphokinase myocardial band data peaked at a late time after burn. FR167653, a specific inhibitor of p38MAPK, prevented the induction of myocardial apoptosis, TNF-alpha expression and myocardial injury after burn. Presumably, the bacterial LPS-induced activation of p38MAPK pathway occurring at an early time after burn induced the subsequent myocardial apoptosis. The p38MAPK-induced activation of pro-inflammatory cytokine appeared to promote the degenerative myocardial injury at a late time after burn. Our present data provided evidence for the hypothesis that the p38MAPK pathway controls both myocardial apoptosis and the pro-inflammatory mediator.
Kita
Toshiro
T
Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. kita@med.uoeh-u.ac.jp
Ogawa
Midori
M
Sato
Hiroaki
H
Kasai
Kentaro
K
Tanaka
Toshiko
T
Tanaka
Noriyuki
N
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002056:Burns / Q000150:complications* / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism*; D006333:Heart Failure / Q000209:etiology*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3