Regulation of matrix metalloproteinases 2 and 9 activities by peroxynitrites in term placentas from type 2 diabetic patients

EVANGELINA CAPOBIANCO, VERÓNICA WHITE1, MARÍA SOSA, INGRID DI MARCO, MARÍA NATALIA BASUALDO, MARÍA CRISTINA FAINGOLD AND ALICIA JAWERBAUM

REPRODUCTIVE SCIENCES

SAGE PUBLICATIONS INC

Año: 2012 vol. 2012 p. 814 - 822

1933-7191

Matrix metalloproteinases (MMPs) are proteolytic enzymes related to a pro-inflammatory environment in several diseases, including diabetes, which can be activated by reactive nitrogen species. This work aimed to determine MMP2 and MMP9 activities and nitration in term placentas from type 2 diabetic patients and verify the hypothesis that peroxynitrites are positive regulators of placental MMP2 and MMP9 activities. For this purpose, term placentas from healthy and type 2 diabetic patients were analysed for MMP2 and MMP9 levels and activities, protein nitration and nitration of MMP2 and MMP9. Villous explants were cultured in the presence of peroxynitrites for further evaluation of MMP2 and MMP9 activities. We found that MMP2 and MMP9 activities were increased in term placentas from diabetic patients. These changes were found even when MMP2 protein concentrations were diminished and MMP9 protein concentrations were not changed in the diabetic group. Increased protein nitration and specific nitration of MMP2 and MMP9 were found in term placentas from diabetic patients. Peroxynitrites were able to increase the activity of placental MMP2 and MMP9. Taken together, this study has shown for first time that peroxynitrites can nitrate and activate MMP2 and MMP9 in the placenta, a nitrative pathway possibly related to MMPs overactivity in the placentas from type 2 diabetic patients.