Accelerated recovery after endotoxic challenge in heat shock-pretreated mice.
The inflammatory response induced by bacterial lipopolysaccharide (LPS) has profound metabolic and physiological effects. Thus hepatic glucose production is depressed after LPS administration, which is, at least in part, due to the downregulation of phosphoenolpyruvate carboxykinase (PEPCK) expression. PEPCK is a key regulatory enzyme of the gluconeogenic pathway. Expression of heat shock proteins (hsps) is a well-conserved response to stress correlated with protection from subsequent insults including inflammation. In this study, the expression of PEPCK was observed to be preserved after injection of LPS in heat shock-pretreated mice. Protection of PEPCK expression was limited to the time after heat shock treatment that displayed hsp70. Comparison of the transcription rate and mRNA levels of PEPCK after LPS injection between mice that were heat shock pretreated or not indicated that the preservation of PEPCK expression was not due to initial protection from the LPS challenge. On the contrary, it was mediated by a rapid recovery after the LPS insult at the level of transcription. These observations suggest that the mechanism of heat shock-mediated protection (stress tolerance) after LPS challenge is due to an increase in the capacity of the organism to recover rather than deterrence from the insult.
Paidas
Charles N
CN
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. cpaidas@jhmi.edu
Mooney
Maria Lourdes
ML
Theodorakis
Nicholas G
NG
De Maio
Antonio
A
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D020127:Recovery of Function; D012769:Shock / Q000503:physiopathology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D004731:Endotoxins; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP)