AMP-activated kinase may suppress NADPH oxidase activation in vascular tissues.
Activation of AMP-activated kinase (AMPK) suppresses NF-kappaB-mediated transcription in endothelial cells exposed to palmitate or TNF-alpha; it also impedes angiotensin II-driven proliferation in vascular smooth muscle cells. These phenomena become predictable if we postulate that AMPK can inhibit activation of NADPH oxidase. Such an effect would make sense from a homeostatic perspective, and moreover there is direct evidence that AMPK suppresses NADPH oxidase activation in neutrophils. New evidence that sub-pathological levels of peroxynitrite can activate AMPK suggest that this enzyme may act as an "early warning signal" for oxidant stress; inhibiting NADPH oxidase would constitute a rational feedback response to such a signal.
McCarty
Mark F
MF
Oasis of Hope Hospital, Tijuana, Mexico. mccarty@pantox.com
Barroso-Aranda
Jorge
J
Contreras
Francisco
F
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D006706:Homeostasis; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019255:NADPH Oxidases; D055372:AMP-Activated Protein Kinases