cyclic-gmp and 5-methyltetrahydrofolate

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.

Topics: 4-Chloro-7-nitrobenzofurazan; 4-Chloromercuribenzenesulfonate; Antioxidants; Arsenicals; Carrier Proteins; Cells, Cultured; Cyclic GMP; Epithelial Cells; Folate Receptors, GPI-Anchored; Free Radical Scavengers; Humans; Imidazoles; Nitric Oxide; Nitric Oxide Donors; Nitrobenzenes; Oxidation-Reduction; Receptors, Cell Surface; Retinal Pigments; Sulfhydryl Compounds; Tetrahydrofolates; Tetranitromethane; Tyrosine

Topics: Animals; Cerebellum; Cyclic GMP; Glutamate Decarboxylase; Glutamates; Glutamic Acid; Kainic Acid; Purkinje Fibers; Pyrrolidines; Rats; Receptors, Cell Surface; Receptors, Kainic Acid; Receptors, Neurotransmitter; Tetrahydrofolates