Retinol and retinoic acid increase MMP-2 activity by different pathways in cultured Sertoli cells

Free Radic Res. 2007 Dec;41(12):1338-47. doi: 10.1080/10715760701717427.

Abstract

Diseases such as atherosclerosis, arthritis and cancer have been related with imbalance in ROS production and failures in regulation of the MMPs. Authors suggested a relationship between MPP activity and ROS. Our research group has demonstrated that retinol 7 microM induced changes in Sertoli cell metabolism linking retinol treatment and oxidative stress. We verified MMP activity in Sertoli cells treated with vitamin A using gelatin zymography. We found that retinol (7 microM) and retinoic acid (1 nM) induced MMP-2 activity in Sertoli cells. Antioxidants reversed retinol-induced but not retinoic acid-induced MMP-2 activity. Moreover, retinol but not retinoic acid increased ROS production quantified by DCFH-DA oxidation. We found that retinol and retinoic acid induced ERK1/2 phosphorylation, but only retinol-increased MMP-2 activity was inhibited by UO126, an ERK1/2 phosphorylation inhibitor. Our findings suggested that retinol-induced MMP-2 activity, but not retinoic acid-induced MMP-2 activity, was related to ERK1/2 phosphorylation and ROS production.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cells, Cultured
  • Male
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 2 / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Sertoli Cells / drug effects
  • Sertoli Cells / enzymology*
  • Tretinoin / pharmacology*
  • Vitamin A / pharmacology*

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Vitamin A
  • Tretinoin
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 2