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dc.contributor.authorTakeuchi, K.
dc.contributor.authorMorizane, Y.
dc.contributor.authorKamami-Levy, C.
dc.contributor.authorSuzuki, J.
dc.contributor.authorKayama, M.
dc.contributor.authorCai, Wenyi
dc.contributor.authorMiller, Joan Whitten
dc.contributor.authorVavvas, Demetrios
dc.date.accessioned2018-02-23T20:58:59Z
dc.date.issued2013
dc.identifierQuick submit: 2013-09-06T02:34:33-04:00
dc.identifier.citationTakeuchi, K., Y. Morizane, C. Kamami-Levy, J. Suzuki, M. Kayama, W. Cai, J. W. Miller, and D. G. Vavvas. “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 of Biological Chemistry 288 (28) (2013): 20581–20591.en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34865298
dc.description.abstractCaveolin-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.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Biochemistry & Molecular Biology (ASBMB)en_US
dc.relation.isversionof10.1074/jbc.M113.460832en_US
dc.relation.isversionofdoi:10.1074/jbc.m113.460832en_US
dash.licenseLAA
dc.subjectAMP-activated kinase (AMPK), Caveolae, Caveolin, Endocytosis, Oxidative Stressen_US
dc.titleAMP-dependent Kinase Inhibits Oxidative Stress-induced Caveolin-1 Phosphorylation and Endocytosis by Suppressing the Dissociation between c-Abl and Prdx1 Proteins in Endothelial Cellsen_US
dc.typeJournal Articleen_US
dc.date.updated2013-09-06T06:35:07Z
dc.description.versionVersion of Recorden_US
dc.rights.holderKimio Takeuchi, Yuki Morizane, Cynthia Kamami-Levy, Jun Suzuki, Maki Kayama, Wenyi Cai, Joan W Miller, and Demetrios G Vavvas
dc.relation.journalJournal of Biological Chemistryen_US
dash.depositing.authorVavvas, Demetrios
dc.date.available2018-02-23T20:58:59Z
dc.identifier.doi10.1074/jbc.M113.460832*
dash.contributor.affiliatedCai, Wenyi
dash.contributor.affiliatedMiller, Joan
dash.contributor.affiliatedVavvas, Demetrios


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