Activation and signaling by the AMP-activated protein kinase in endothelial cells.
The AMP-activated protein kinase (AMPK) was initially identified as the kinase that phosphorylates the 3-hydroxy 3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. As the name suggests, the AMPK is activated by increased intracellular concentrations of AMP, and is generally described as a "metabolite-sensing kinase" and when activated initiates steps to conserve cellular energy. Although there is a strong link between the activity of the AMPK and metabolic control in muscle cells, the activity of the AMPK in endothelial cells can be regulated by stimuli that affect cellular ATP levels, such as hypoxia as well as by fluid shear stress, Ca(2+)-elevating agonists, and hormones such as adiponectin. To date the AMPK in endothelial cells has been implicated in the regulation of fatty acid oxidation, small G protein activity and nitric oxide production as well as inflammation and angiogenesis. Moreover, there is evidence indicating that the activation of the AMPK may help to prevent the vascular complications associated with the metabolic syndrome.
Fisslthaler
Beate
B
Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Fleming
Ingrid
I
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000201:enzymology; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004734:Energy Metabolism; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D020536:Enzyme Activators; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases