%0 Journal Article %J J Biol Chem %D 2013 %T AMP-dependent kinase inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis by suppressing the dissociation between c-Abl and Prdx1 proteins in endothelial cells %A Takeuchi, Kimio %A Morizane, Yuki %A Kamami-Levy, Cynthia %A Suzuki, Jun %A Kayama, Maki %A Cai, Wenyi %A Miller, Joan W %A Vavvas, Demetrios G %K Albumins %K Aminoimidazole Carboxamide %K AMP-Activated Protein Kinases %K Blotting, Western %K Caveolin 1 %K Cells, Cultured %K Dipyridamole %K Endocytosis %K Enzyme Activation %K Human Umbilical Vein Endothelial Cells %K Humans %K Hydrogen Peroxide %K Isoenzymes %K Microscopy, Confocal %K Oxidants %K Oxidative Stress %K Peroxiredoxins %K Phosphorylation %K Protein Binding %K Proto-Oncogene Proteins c-abl %K Ribonucleotides %K RNA Interference %K Tubercidin %X Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1. %B J Biol Chem %V 288 %P 20581-91 %8 2013 Jul 12 %G eng %N 28 %1 http://www.ncbi.nlm.nih.gov/pubmed/23723070?dopt=Abstract %R 10.1074/jbc.M113.460832