title: Glucose-mediated tyrosine nitration in adipocytes: targets and consequences.
abstract: Hyperglycemia, a key factor in insulin resistance and diabetic pathology, is associated with cellular oxidative stress that promotes oxidative protein modifications. We report that protein nitration is responsive to changes in glucose concentrations in 3T3-L1 adipocytes. Alterations in the extent of tyrosine nitration as well as the cellular nitroproteome profile correlated tightly with changing glucose concentrations. The target proteins we identified are involved in fatty acid binding, cell signaling, protein folding, energy metabolism, antioxidant capacity, and membrane permeability. The nitration of adipocyte fatty acid binding protein (FABP4) at Tyr19 decreases, similar to phosphorylation, the binding of palmitic acid to the fatty acid-free protein. This potentially alters intracellular fatty acid transport, nuclear translocation of FABP4, and agonism of PPAR gamma. Our results suggest that protein tyrosine nitration may be a factor in obesity, insulin resistance, and the pathogenesis of diabetes.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44118, USA. koeckt@ccf.org
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.forename: John W
authors.initials: JW
authors.lastname: Crabb
authors.forename: Mike
authors.initials: M
authors.lastname: Kinter
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Stuehr
authors.forename: Kulwant S
authors.initials: KS
authors.lastname: Aulak
mesh_terms: D041721:3T3-L1 Cells; D021581:Active Transport, Cell Nucleus; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009566:Nitrates; D019308:Palmitic Acid; D014443:Tyrosine; D005947:Glucose