Targeting the ubiquitin proteasome pathway for the treatment of septic shock in patients.
Endotoxic shock is a serious systemic inflammatory response to an external biological stressor. The responsiveness of NF-kappaB is built upon rapid protein modification and degradation involving the ubiquitin proteasome pathway. Using transgenic mice, we have obtained in vivo evidence that interference with this pathway can alleviate the symptoms of toxic shock. We posit that administration of proteasome inhibitors may enhance the survival of patients with septic shock.
Brun
Jan
J
Ottawa Health Research Institute, Ottawa, ON, Canada K1Y 4E9. jzbrun@yahoo.com
Gray
Douglas A
DA
D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction; D025801:Ubiquitin / Q000187:drug effects*
D016328:NF-kappa B; D011480:Protease Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
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