Regulation of the reduced-folate transporter by nitric oxide in cultured human retinal pigment epithelial cells.
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.
Smith
S B
SB
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, USA. sbsmith@mail.mcg.edu
Huang
W
W
Chancy
C
C
Ganapathy
V
V
D009327:4-Chloro-7-nitrobenzofurazan / Q000494:pharmacology; D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010084:Oxidation-Reduction; D011956:Receptors, Cell Surface; D012168:Retinal Pigments / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism; D013774:Tetranitromethane / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D000975:Antioxidants; D001152:Arsenicals; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D016166:Free Radical Scavengers; D007093:Imidazoles; D020030:Nitric Oxide Donors; D009578:Nitrobenzenes; D011956:Receptors, Cell Surface; D012168:Retinal Pigments; D013438:Sulfhydryl Compounds; D013763:Tetrahydrofolates; C029341:oxophenylarsine; D009569:Nitric Oxide; C034442:4-nitrobenzenesulfonyl fluoride; D014443:Tyrosine; D002731:4-Chloromercuribenzenesulfonate; D009327:4-Chloro-7-nitrobenzofurazan; D006152:Cyclic GMP; D013774:Tetranitromethane; C005984:5-methyltetrahydrofolate; C012160:N-acetylimidazole