The effect of AMP-activated protein kinase and its activator AICAR on the metabolism of human umbilical vein endothelial cells.
In several non-vascular tissues in which it has been studied, AMP-activated protein kinase (AMPK) appears to modulate the cellular response to stresses such as ischemia. In liver and muscle, it phosphorylates and inhibits acetyl CoA carboxylase (ACC), leading to an increase in fatty acid oxidation; and in muscle, its activation is associated with an increase in glucose transport. Here we report the presence of both AMPK and ACC in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with 2 mM AICAR, an AMPK activator, caused a 5-fold activation of AMPK, which was accompanied by a 70% decrease in ACC activity and a 2-fold increase in fatty acid oxidation. Surprisingly, glucose uptake and glycolysis, the dominant energy-producing pathway in HUVEC, were diminished by 40-60%. Despite this, cellular ATP levels were increased by 35%. Thus activation of AMPK by AICAR is associated with major alterations in endothelial cell energy balance. Whether these alterations protect the endothelium during ischemia or other stresses remains to be determined.
Dagher
Z
Z
Departments of Medicine and Physiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Ruderman
N
N
Tornheim
K
K
Ido
Y
Y
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology*; D014471:Umbilical Veins
D007004:Hypoglycemic Agents; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D019308:Palmitic Acid; D000620:Aminoimidazole Carboxamide; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D005947:Glucose