title: Regulation of matrix metalloproteinases 2 and 9 activities by peroxynitrites in term placentas from type 2 diabetic patients.
abstract: Matrix metalloproteinases (MMPs) are proteolytic enzymes related to a proinflammatory environment in several diseases, including diabetes, which can be activated by reactive nitrogen species. This work aimed to determine MMP-2 and MMP-9 activities and nitration in term placentas from type 2 diabetic patients and verify the hypothesis that peroxynitrites are positive regulators of placental MMP-2 and MMP-9 activities. For this purpose, term placentas from healthy and type 2 diabetic patients were analyzed for MMP-2 and MMP-9 levels and activities, protein nitration, and nitration of MMP-2 and MMP-9. Villous explants were cultured in the presence of peroxynitrites for further evaluation of MMP-2 and MMP-9 activities. We found that MMP-2 and MMP-9 activities were increased in term placentas from diabetic patients. These changes were found even when MMP-2 protein concentrations were diminished and MMP-9 protein concentrations were not changed in the diabetic group. Increased protein nitration and specific nitration of MMP-2 and MMP-9 were found in term placentas from diabetic patients. Peroxynitrites were able to increase the activity of placental MMP-2 and MMP-9. Taken together, this study has shown for first time that peroxynitrites can nitrate and activate MMP-2 and MMP-9 in the placenta, a nitrative pathway possibly related to MMPs overactivity in the placentas from type 2 diabetic patients.
authors.affiliation: Laboratory of Reproduction and Metabolism. CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.forename: Verónica
authors.initials: V
authors.lastname: White
authors.forename: María
authors.initials: M
authors.lastname: Sosa
authors.forename: Ingrid
authors.initials: I
authors.lastname: Di Marco
authors.forename: María Natalia
authors.initials: MN
authors.lastname: Basualdo
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Faingold
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000201:enzymology*; D046509:Tissue Culture Techniques
chemical_list: D009566:Nitrates; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9