Hyperoxia increases hepatic arginase expression and ornithine production in mice.
Hyperoxic exposure affects the levels and activities of some hepatic proteins. We tested the hypothesis that hyperoxic exposure would result in greater hepatic .NO concentrations. C3H/HeN mice were exposed to >95% O(2) for 72 or 96 h and compared to room air-breathing controls. In contrast to our working hypothesis, exposure to >95% O(2) for 96 h decreased hepatic nitrite/nitrate NO(X) concentrations (10.9 +/- 2.2 nmol/g liver versus 19.3 +/- 2.4 nmol/g liver in room air, P < 0.05). The hepatic levels of endothelial NO synthase (eNOS) and inducible NOS (iNOS) proteins were not different among the groups. The arginases, which convert L-arginine to urea and L-ornithine, may affect hepatic NOS activities by decreasing L-arginine bioavailability. Hepatic ornithine concentrations were greater in hyperoxic animals than in controls (318 +/- 18 nmol/g liver in room air, and 539 +/- 64, and 475 +/- 40 at 72 and 96 h of hyperoxia, respectively, P < 0.01). Hepatic arginase I protein levels were greater in hyperoxic animals than in controls. Hepatic carbamoyl phosphate synthetase (CPS) protein levels and activities were not different among groups. These results indicate that increases in hepatic levels of arginase I in mice exposed to hyperoxia may diminish .NO production, as reflected by lower liver levels of NO(X). The resultant greater hepatic ornithine concentrations may represent a mechanism to facilitate tissue repair, by favoring the production of polyamines and/or proline.
Center for Developmental Pharmacology and Toxicology, Columbus Children's Research Institute, Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA.
Daniel T
DT
Malleske
Lynette K
LK
Rogers
Sean M
SM
Velluci
Tamara L
TL
Young
Min S
MS
Park
Donald W
DW
Long
Stephen E
SE
Welty
Charles V
CV
Smith
Leif D
LD
Nelin
D000818:Animals; D001119:Arginase / Q000378:metabolism*; D002956:Citrulline / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase; D018496:Hyperoxia / Q000201:enzymology*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009952:Ornithine / Q000096:biosynthesis*
D002956:Citrulline; D009952:Ornithine; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D005980:Glutathione Reductase; D001119:Arginase; D005978:Glutathione; D019803:Glutathione Disulfide