PPARα and PPARγ regulate the nucleoside transporter hENT1

Biochem Biophys Res Commun. 2012 Mar 9;419(2):405-11. doi: 10.1016/j.bbrc.2012.02.035. Epub 2012 Feb 11.

Abstract

Human equilibrative nucleoside transporter 1 (hENT1) is an important determinant for nucleoside analog based chemotherapy success. Preliminary data suggest hENT1 regulation by PPARs. Using A2780 cells, we investigated the role of PPARs on hENT1 expression and activity. PPARα and PPARγ agonists, Wy14,643 and RGZ, increased hENT1 expression, but only PPARα activation or overexpression resulted in higher hENT1 transport activity. On the other hand, promoter analysis showed two putative PPRE in hENT1 promoter and luciferase-coupled promoter constructs were generated and analyzed. Our results suggest that PPARα-but not PPARγ-mediated expression regulation of hENT1 is PPRE-dependent. In conclusion, PPARα and PPARγ activation modulate hENT1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Equilibrative Nucleoside Transporter 1 / genetics*
  • Gene Expression Regulation*
  • Humans
  • PPAR alpha / agonists
  • PPAR alpha / metabolism*
  • PPAR gamma / agonists
  • PPAR gamma / metabolism*
  • Promoter Regions, Genetic
  • Pyrimidines / pharmacology
  • Transfection
  • Up-Regulation

Substances

  • Equilibrative Nucleoside Transporter 1
  • PPAR alpha
  • PPAR gamma
  • Pyrimidines
  • SLC29A1 protein, human
  • pirinixic acid