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

被引:23
|
作者
Smith, SB
Huang, W
Chancy, C
Ganapathy, V
机构
[1] Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA
[2] Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA
[3] Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA
关键词
reduced-folate transporter; nitric oxide; N-5-methyltetrahydrofolate; folate transport; human retinal pigment epithelium;
D O I
10.1006/bbrc.1999.0452
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 N-5-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. (C) 1999 Academic Press.
引用
收藏
页码:279 / 283
页数:5
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