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

doi:10.1006/bbrc.1999.0452

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

Cellular Biology and Anatomy

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English (US)
Pages (from-to)	279-283
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	257
Issue number	2
DOIs	https://doi.org/10.1006/bbrc.1999.0452
State	Published - Apr 13 1999

Keywords

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

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1006/bbrc.1999.0452

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

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.",

keywords = "Folate transport, Human retinal pigment epithelium, N-methyltetrahydrofolate, Nitric oxide, Reduced-folate transporter",

author = "Smith, {Sylvia B} and Wei Huang and Christy Chancy and Vadivel Ganapathy",

note = "Funding Information: Supported by EY09682 and HD 33347, the Medical College of Georgia Research Institute, and by an unrestricted grant from Research to Prevent Blindness, Inc., New York, to the Department of Ophthalmology, Medical College of Georgia.",

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AU - Huang, Wei

AU - Chancy, Christy

AU - Ganapathy, Vadivel

N1 - Funding Information: Supported by EY09682 and HD 33347, the Medical College of Georgia Research Institute, and by an unrestricted grant from Research to Prevent Blindness, Inc., New York, to the Department of Ophthalmology, Medical College of Georgia.

PY - 1999/4/13

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N2 - 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.

AB - 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.

KW - Folate transport

KW - Human retinal pigment epithelium

KW - N-methyltetrahydrofolate

KW - Nitric oxide

KW - Reduced-folate transporter

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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