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Regulation of Matrix Metalloproteinases 2 and 9 Activities by Peroxynitrites in Term Placentas From Type 2 Diabetic Patients

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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.

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Authors and Affiliations

  1. Laboratory of Reproduction and Metabolism. CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th floor, 1121ABG, Buenos Aires, Argentina

    Evangelina Capobianco PhD, Verónica White PhD, María Sosa MD & Alicia Jawerbaum PhD

  2. Obstetric Department, Hospital Materno Infantil “Ramón Sardá”, Buenos Aires, Argentina

    Ingrid Di Marco MD & María Natalia Basualdo MD

  3. Hospital César Milstein (ex Hospital Francés), CABA, Buenos Aires, Argentina

    María Cristina Faingold MD

Authors
  1. Evangelina Capobianco PhD
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  2. Verónica White PhD
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  3. María Sosa MD
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  4. Ingrid Di Marco MD
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  5. María Natalia Basualdo MD
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  6. María Cristina Faingold MD
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  7. Alicia Jawerbaum PhD
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Correspondence to Alicia Jawerbaum PhD.

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Capobianco, E., White, V., Sosa, M. et al. Regulation of Matrix Metalloproteinases 2 and 9 Activities by Peroxynitrites in Term Placentas From Type 2 Diabetic Patients. Reprod. Sci. 19, 814–822 (2012). https://doi.org/10.1177/1933719111434544

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