Acrolein-induced oxidative stress in NAD(P)H Oxidase Subunit gp91phox knock-out mice and its modulation of NFκB and CD36.
An essential component of NAD(P)H, gp91phox, maintains the functionality of the enzyme in producing oxygen radicals. NAD(P)H oxidase plays an important role in oxidative stress but its precise contribution in acrolein-induced toxicity was not explored. We examined the involvement of NAD(P)H oxidase and other oxidant system in acrolein toxicity using gp91phox knockout mice. Male gp91phox knockout (KO) mice (20-25 gm) or wild type (WT) controls were treated with acrolein (0.5 μg/kg; 1 week). Animals were sacrificed and the liver was used to determine biochemical parameters. Knockout mice generated low (1.43 ±.02 pg/μg protein) free radicals as evident in 8-Isoprostane compared with the WT mice (2.19 ± 0.1). Acrolein increased 8-Isoprostane in WT (P<.05) and KO (p<.05) mice. Xanthine Oxidase (XO) activity was higher (p<.05) in KO (0.56 ± 0.06 μ unit/μg protein) than WT mice. Acrolein increased XO in KO mice, but significantly increased it only in WT. Cycloxygenase (COX) activity was not different between WT and KO mice, although acroelin increased COX in WT. Knockout mice exhibited a significantly low (2.1 ± 0.2 μmol/mg protein) total antioxidant status (TAS) compared with the WT (3.5 ± 0.3). Acrolein reduced TAS in both WT and KO mice equally. Baseline NFκB was significantly higher in KO mice, although acrolein increased NFκB in WT but not in KO. CD36 was higher (p<.05) in KO mice than the WT and acrolein increased (p<.05) CD36 further in KO but not in WT mice. These data suggest that NAD(P)H oxidase contributes significantly in acrolein-induced oxidative stress. We also suggests that in the absence of NAD(P)H oxidase XO plays a definitive role together with reduced antioxidant ability to compound the toxic effects of acrolein. We propose that in absence of NAD(P)H oxidase a different signaling process may involve that utilizes CD36 besides NFκB.
Zivar
Z
Yousefipour
Chelsea
C
Zhang
Mahdieh
M
Monfareed
James
J
Walker
Mohammad
M
Newaz
D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000378:metabolism
D018955:CD36 Antigens; D004785:Environmental Pollutants; D016328:NF-kappa B; C075750:8-epi-prostaglandin F2alpha; D000171:Acrolein; D015237:Dinoprost; D014969:Xanthine Oxidase; D019255:NADPH Oxidases