Burn-related metabolic and signaling changes in rat brain.
Postburn alterations in the morphology and metabolism of brain tissue have been previously reported. It was demonstrated in our previous study that thermal injury decreased glucose usage in rat brain during the ebb phase. The cellular and molecular signaling events that trigger the pathophysiologic alterations, however, have not yet been characterized. In the present report, the authors have examined the effect of burn injury on mitogen-activated protein kinases (MAPKs) activities and insulin signaling in the brain tissue. Rats were subjected to 50% total body surface area full thickness scald injury. Brain samples were collected at 6 hours after injury. Tissue lysates were analyzed for MAPKs activities, insulin receptor substrate (IRS)-1 expression, and Akt activity which were determined by western blot and immunoprecipitation. Burn injury stimulated the stress-responsive components, SAPK/JNK, p38 MAP kinase and p44/42 MAP kinase, and increased IRS-1 expression and Akt activity. There was no change, however, on the phosphorylation of Ser307 of IRS-1 in brain tissue. The present data is consistent with the hypothesis that activation of the three major MAPKs pathways appears to be events involved in the mechanisms of burn injury induced insulin resistance and encephalopathy. Changes in signal transduction pathways in the brain after burn injury provide the underlying molecular mechanism of neurologic abnormalities (burn encephalopathy) that occur in burn patients.
Zhang
Qin
Q
Department of Surgery, Massachusetts General Hospital, and Shriners Hospital for Children, Boston, MA 02114, USA.
Carter
Edward A
EA
Ma
Bangyi
B
Fischman
Alan J
AJ
Tompkins
Ronald G
RG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002056:Burns / Q000150:complications* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D023421:Models, Animal; D051381:Rats; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8