Inhibition of NADPH supply by 6-aminonicotinamide: effect on glutathione, nitric oxide and superoxide in J774 cells

被引：49

作者：

Hothersall, JS ^{[1
]}

Gordge, M ^{[1
]}

Noronha-Dutra, AA ^{[1
]}

机构：

[1] UCL, Inst Urol & Nephrol, Dept Med, Ctr Nephrol, London W1P 7PN, England

来源：

FEBS LETTERS | 1998年 / 434卷 / 1-2期

关键词：

nitric oxide; glutathione; superoxide; NADPH; 6-aminonicotinamide; macrophage;

D O I：

10.1016/S0014-5793(98)00959-4

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：

We have examined the integrity of J774 cell nitric oxide (NO) production and glutathione maintenance, whilst NADPH supply was compromised by inhibition of the pentose pathway with 6-aminonicotinamide. In resting cells 6-phosphogluconate accumulation began after 4 h and glutathione depletion after 24 h of 6-aminonicotinamide treatment. Cellular activation by lipopolysaccharide/interferon-lambda decreased glutathione by similar to 50% and synchronous 6-aminonicotinamide treatment exacerbated this to 31.2% of control (P < 0.05), In activated cells NO, production was inhibited by 60% with 6-aminonicotinamide (P < 0.01), and superoxide production by 50% (P < 0.01) in zymosan-activated cells. NADPH production via the pentose pathway is therefore important to sustain macrophage NO production whilst maintaining protective levels of glutathione. (C) 1998 Federation of European Biochemical Societies.

引用

页码：97 / 100

页数：4

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