title: Inhibition of NADPH supply by 6-aminonicotinamide: effect on glutathione, nitric oxide and superoxide in J774 cells.
abstract: 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 approximately 50% and synchronous 6-aminonicotinamide treatment exacerbated this to 31.2% of control (P < 0.05). In activated cells NO2- 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.
authors.affiliation: Centre for Nephrology, Department of Medicine, University College London, UK. j.hothersall@ucl.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Hothersall
authors.forename: M
authors.initials: M
authors.lastname: Gordge
authors.forename: A A
authors.initials: AA
authors.lastname: Noronha-Dutra
mesh_terms: D015120:6-Aminonicotinamide / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009249:NADP / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013723:Teratogens / Q000494:pharmacology*
chemical_list: D013723:Teratogens; D013481:Superoxides; D009569:Nitric Oxide; D015120:6-Aminonicotinamide; D009249:NADP; D005978:Glutathione