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

FEBS Letters

Gordge, Michael¹  Hothersall, John S¹  Noronha-Dutra, Alberto A¹ 

[1] Centre for Nephrology, Department of Medicine, Institute of Urology and Nephrology, University College London, 48 Riding House St, London W1P 7PN, UK

关键词: Nitric oxide;    Glutathione;    Superoxide;    NADPH;    6-Aminonicotinamide;    Macrophage;   

DOI  :  10.1016/S0014-5793(98)00959-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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-λ decreased glutathione by ∼50% and synchronous 6-aminonicotinamide treatment exacerbated this to 31.2% of control (P<0.05). In activated cells NO⁻ ₂ 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.

【 授权许可】

Unknown