Targets of tyrosine nitration in diabetic rat retina.

Targets of tyrosine nitration in diabetic rat retina. Research Abstract Details 

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Targets of tyrosine nitration in diabetic rat retina. Abstract Text:

Diabetic retinopathy, a retinal vascular disease, is inhibited in animals treated with aminoguanidine, an inhibitor of inducible nitric-oxide synthase. This treatment also reduces retinal protein nitration, which is greater in diabetic rat retina than nondiabetic retina. As an approach to understanding the molecular mechanisms of diabetic retinopathy, we sought the identity of nitrotyrosine-containing proteins in retina from streptozotocin-induced diabetic rats and in a rat retinal Müller cell line grown in high glucose (25 mM). Anti-nitrotyrosine immunoprecipitation products from rat retina and Müller cells were analyzed by LC-MS/MS. Ten nitrated proteins in diabetic rat retina and three nitrated proteins in Müller cells grown in high glucose were identified; three additional nitrotyrosine-containing proteins were tentatively identified from diabetic retina. The identified nitrotyrosine-containing proteins participate in a variety of processes including glucose metabolism, signal transduction, and transcription/translation. Among the nitrated proteins were insulin-responsive glucose transporter type 4 (GLUT-4), which has been implicated previously in the pathogenesis of diabetes mellitus; exocyst complex component Exo70, which functions in insulin-stimulated glucose uptake of GLUT-4-containing vesicles; and fibroblast growth factor receptor 2, which influences retinal vascularization via fibroblast growth factor signaling. Nitration of tyrosine phosphorylation sites were identified in five proteins, including GLUT-4, exocyst complex component Exo70, protein-tyrosine phosphatase eta, sensory neuron synuclein, and inositol trisphosphate receptor 3. Quantitation of nitration and phosphorylation at common tyrosine modification sites in GLUT-4 and protein-tyrosine phosphatase eta from diabetic and nondiabetic animals suggests that nitration reduced tyrosine phosphorylation approximately 2X in these proteins from diabetic retina. The present results provide new insights regarding tyrosine nitration and its potential role in the molecular mechanisms of diabetic retinopathy.

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Targets of tyrosine nitration in diabetic rat retina. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular & cellular proteomics : MCP

VOLUME: 7

Page Numbers: 864-74

Journal Abbreviation: Mol. Cell Proteomics

ISSN: 1535-9484

DAY: 28

MONTH: 12

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 101125647

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Grant and Affiliation Information for Targets of tyrosine nitration in diabetic rat retina.

AFFILIATION: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Country: United States

AGENCY: United States NEI

GRANT: EY15638

ACRONYM: EY

MEDLINETA: Mol Cell Proteomics

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