| Roles of AMP-Activated Protein Kinase in Diabetes-Induced Retinal Inflammation. | |
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MedLine Citation:
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PMID: 22058332 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Purpose.AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. The aim of the present study was to elucidate the roles of AMPK in the pathogenesis of diabetic retinopathy using known AMPK activators resveratrol and AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) to a mouse model.Methods.C57BL/6 mice with streptozotocin-induced diabetes were treated with resveratrol orally at the dose of 50 mg/kg for 7 days or with AICAR intraperitoneally at the dose of 100 mg/kg 24 hours before sacrifice. Retinal protein levels of phosphorylated and total AMPK, phosphorylated nuclear factor (NF)-kB p65, intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor (VEGF) were evaluated by western blotting or enzyme-linked immunosorbent assay. Retinal activity of sirtuin (SIRT) 1 was measured by deacetylase fluorometric assay. Leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique.Results.Induction of diabetes to mice led to retinal AMPK dephoshorylation, which was significantly reversed by either resveratrol or AICAR. Importantly, either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-kB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion together with retinal expression of ICAM-1 and VEGF.Conclusions.The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of AMPK pathway, leading subsequently to SIRT1 deactivation and NF-kB activation. Our data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy. |
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Authors:
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Shunsuke Kubota; Yoko Ozawa; Toshihide Kurihara; Mariko Sasaki; Kenya Yuki; Seiji Miyake; Kousuke Noda; Susumu Ishida; Kazuo Tsubota |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-4 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: - ISSN: 1552-5783 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Laboratory of Retinal Cell Biology. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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