Lung poly(ADP-ribose) and NAD+ concentrations during hyperoxia and niacin deficiency in the Fischer-344 rat.
Sublethal exposure to hyperoxia in vivo induces oxidative damage that leads to destruction of the pulmonary endothelium, pleural effusion, and eventual pulmonary fibrosis. DNA is a potential target for reactive oxygen species in this system; the principle types of damage to DNA during hyperoxia are single-strand breaks and oxidant damage to bases. Poly(ADP-ribosyl)ation, a posttranslational modification of nuclear proteins, is stimulated by strand breaks in DNA and is required for effective repair of many types of DNA lesions. In this study we have measured lung tissue NAD+ and poly(ADP-ribose) concentrations in response to hyperoxia and niacin deficiency in rats. Male weaning Fischer-344 rats consumed niacin-deficient (ND) or niacin-replete pair-fed (PF) diets for 7 d. Rats from each diet group (n = 6) were then housed in normobaric 85% oxygen for 5 d. Normoxic controls were maintained in air. Hyperoxia increased lung poly(ADP-ribose) concentration by 35% in PF rats, but did not significantly increase levels in ND rats. Niacin deficiency decreased lung NAD+ in normoxic rats, but surprisingly, this deficit was partially reversed by hyperoxia. Liver NAD+ levels increased by 21% during hyperoxia in both diet groups. Heart and kidney NAD+ were unaffected by hyperoxia. Blood was the only tissue measured in which NAD+ was decreased by hyperoxia. Dietary treatment did not affect the increase in the lung wt/b. wt. ratio resulting from hyperoxia. This is the first report in the literature of lung tissue poly(ADP-ribose) measurement. Results show that hyperoxia causes a marked increase in lung poly (ADP-ribose) concentration, but also suggest an adaptation of whole-animal NAD+ metabolism to hyperoxia during niacin deficiency.
Rawling
J M
JM
Department of Nutritional Sciences, College of Biological Sciences, University of Guelph, Ontario, Canada.
ApSimon
M M
MM
Kirkland
J B
JB
D000818:Animals; D001835:Body Weight; D004249:DNA Damage; D004032:Diet; D005609:Free Radicals / Q000494:pharmacology; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000097:blood / Q000378:metabolism*; D009525:Niacin / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D009929:Organ Size; D018384:Oxidative Stress; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D005609:Free Radicals; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D009525:Niacin