Alterations in arginine metabolic enzymes in trauma.
Arginine is the sole substrate for nitric oxide (NO) synthesis by NO synthases (NOS) and promotes the proliferation and maturation of human T-cells. Arginine is also metabolized by the enzyme arginase, producing urea and ornithine, the precursor for polyamine production. We sought to determine the molecular mechanisms regulating arginase and NOS in splenic immune cells after trauma. C3H/HeN mice underwent laparotomy as simulated moderate trauma or anesthesia alone (n = 24 per group). Six, 12, 24, or 48 h later, 6 animals from each group were sacrificed, and splenectomy was performed and plasma collected. Six separate animals had neither surgery nor anesthesia and were sacrificed to provide resting values (t = 0 h). Spleen arginase I and II and iNOS mRNA abundance, arginase I protein expression, and arginase activity were determined. Plasma NO metabolites (nitrite + nitrate) were also measured. Trauma increased spleen arginase I protein expression and activity (P = 0.01) within 12 and for at least 48 h after injury and coincided with up-regulated arginase I mRNA abundance at 24 h. Neither arginase II nor iNOS mRNA abundance in the spleen was significantly increased by trauma at 24 h. Plasma nitrite + nitrate was decreased in animals 48 h post-injury compared to anesthesia controls (P < 0.05). Trauma induces up-regulation of arginase I gene expression in splenic immune cells within 24 h of injury. Arginase II is not significantly up-regulated at that time point. Arginase I, rather than iNOS appears to be the dominant route for arginine metabolism in splenic immune cells 24 h after trauma.
Vascular and Trauma/Critical Care Research Program, University of Kentucky College of Medicine, Lexington 40536-0298, USA.
A C
AC
Bernard
S K
SK
Mistry
S M
SM
Morris
W E
WE
O'Brien
B J
BJ
Tsuei
M E
ME
Maley
L A
LA
Shirley
P A
PA
Kearney
B R
BR
Boulanger
J B
JB
Ochoa
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism*
D004798:Enzymes; D007527:Isoenzymes; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001119:Arginase