INHIBITION OF NADPH SUPPLY BY 6-AMINONICOTINAMIDE - EFFECT ON GLUTATHIONE, NITRIC-OXIDE AND SUPEROXIDE IN J774 CELLS

We have examined the integrity of J774 cell nitric oxide (NO) producti on and glutathione maintenance, whilst NADPH supply was compromised by inhibition of the pentose pathway with 6-aminonicotinamide. In restin g cells 6-phosphogluconate accumulation began after 4 h and glutathion e depletion after 24 h of 6-aminonicotinamide treatment. Cellular acti vation by lipopolysaccharide/interferon-lambda decreased glutathione b y similar to 50% and synchronous 6-aminonicotinamide treatment exacerb ated this to 31.2% of control (P < 0.05), In activated cells NO, produ ction was inhibited by 60% with 6-aminonicotinamide (P < 0.01), and su peroxide production by 50% (P < 0.01) in zymosan-activated cells. NADP H production via the pentose pathway is therefore important to sustain macrophage NO production whilst maintaining protective levels of glut athione. (C) 1998 Federation of European Biochemical Societies.