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

Sylvia B Smith, Wei Huang, Christy Chancy, Vadivel Ganapathy

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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.

Original languageEnglish (US)
Pages (from-to)279-283
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Apr 13 1999



  • Folate transport
  • Human retinal pigment epithelium
  • N-methyltetrahydrofolate
  • Nitric oxide
  • Reduced-folate transporter

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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