Alterations in N-acetylation of 3-methylhistidine in endotoxemic parenterally fed rats.
N-methylhistidine (3-meH) is endogenously released during muscle catabolism and serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the urine as the N-acetyl derivative. It has been reported that the percent of non-acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate these reports we randomized 39 male Sprague-Dawley rats (157-213 g) to receive parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg.kg-1.d-1 for 48 h. All animals received isocaloric and isonitrogenous PN 24 h before and throughout the study with water ad libitum. Total 3-meH excretion was significantly increased (P < 0.05) in the LPS-6 (470 +/- 136 micrograms/48 h) and LPS-12 (557 +/- 171 micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6 (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/48 h) groups (P < 0.05). Percent NA-3-meH increased significantly from 12.7 +/- 3.9% in the PN group to 19.8 +/- 8.0 and 39.9 +/- 12.8% in the LPS-6 and LPS-12 groups, respectively (P < 0.05). No significant changes in acetyl 3-meH were found between groups. These data suggest that either saturation or inhibition of acetylation pathways occurs with increasing levels of stress. Due to the disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia, only total 3-meH should be used as an indicator of protein turnover in rats.
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee 38163, USA. dkuhl@utmem1.utmem.edu
D A
DA
Kuhl
J F
JF
Mouser
J T
JT
Methvin
E B
EB
Hak
L J
LJ
Hak
R N
RN
Dickerson
D000107:Acetylation; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008762:Methylhistidines / Q000378:metabolism* / Q000652:urine; D010288:Parenteral Nutrition; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D008762:Methylhistidines; C028118:3-methylhistidine