Regulation of the reduced-folate transporter by nitric oxide in cultured human retinal pigment epithelial cells

Biochem Biophys Res Commun. 1999 Apr 13;257(2):279-83. doi: 10.1006/bbrc.1999.0452.

Abstract

The regulation of the reduced-folate transporter (RFT) by nitric oxide (NO) was analyzed in human retinal pigment epithelial (HRPE) cells. NO inhibited specifically and reversibly the uptake of N5-methyltetrahydrofolate by a cGMP-independent mechanism. The inhibition was associated with a decrease in substrate affinity. The NO-induced inhibition was prevented by antioxidants and NO scavengers. Agents capable of modifying thiol groups in proteins inhibited RFT, indicating that the likely mechanism of NO-induced inhibition is via modification of essential thiol groups in this protein. These studies suggest that NO produced during retinal disease may affect the function of RFT in adjacent RPE cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Chloro-7-nitrobenzofurazan / pharmacology
  • 4-Chloromercuribenzenesulfonate / pharmacology
  • Antioxidants / pharmacology
  • Arsenicals / pharmacology
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Cyclic GMP / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Folate Receptors, GPI-Anchored
  • Free Radical Scavengers / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / antagonists & inhibitors
  • Nitric Oxide Donors / pharmacology
  • Nitrobenzenes / pharmacology
  • Oxidation-Reduction
  • Receptors, Cell Surface*
  • Retinal Pigments / metabolism*
  • Sulfhydryl Compounds / metabolism
  • Tetrahydrofolates / metabolism
  • Tetranitromethane / pharmacology
  • Tyrosine / metabolism

Substances

  • Antioxidants
  • Arsenicals
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Free Radical Scavengers
  • Imidazoles
  • Nitric Oxide Donors
  • Nitrobenzenes
  • Receptors, Cell Surface
  • Retinal Pigments
  • Sulfhydryl Compounds
  • Tetrahydrofolates
  • oxophenylarsine
  • Nitric Oxide
  • 4-nitrobenzenesulfonyl fluoride
  • Tyrosine
  • 4-Chloromercuribenzenesulfonate
  • 4-Chloro-7-nitrobenzofurazan
  • Cyclic GMP
  • Tetranitromethane
  • 5-methyltetrahydrofolate
  • N-acetylimidazole