@article {1363212,
	title = {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},
	journal = {J Biol Chem},
	volume = {288},
	number = {28},
	year = {2013},
	month = {2013 Jul 12},
	pages = {20581-91},
	abstract = {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.},
	keywords = {Albumins, Aminoimidazole Carboxamide, AMP-Activated Protein Kinases, Blotting, Western, Caveolin 1, Cells, Cultured, Dipyridamole, Endocytosis, Enzyme Activation, Human Umbilical Vein Endothelial Cells, Humans, Hydrogen Peroxide, Isoenzymes, Microscopy, Confocal, Oxidants, Oxidative Stress, Peroxiredoxins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-abl, Ribonucleotides, RNA Interference, Tubercidin},
	issn = {1083-351X},
	doi = {10.1074/jbc.M113.460832},
	author = {Takeuchi, Kimio and Morizane, Yuki and Kamami-Levy, Cynthia and Suzuki, Jun and Kayama, Maki and Cai, Wenyi and Miller, Joan W and Vavvas, Demetrios G}
}
