Unchanged capacity of urea synthesis during acute phase response in rats.
BACKGROUND
The acute phase response presents a catabolic event related to increased waste of amino-N via hepatic urea synthesis despite an increased need for amino-N incorporation into acute phase proteins. In our previous studies, tumour necrosis factor-α (TNF-α) acutely up-regulated the in vivo capacity of urea-nitrogen synthesis (CUNS) in rats before the hepatic acute phase response was established. To extend these observations, this study aimed to clarify the regulation of N elimination via urea during the later stages of the acute phase response.


METHODS
Twenty-four hours after i.v. injection of 25 μg kg(-1) TNF-α or placebo, we determined the in vivo CUNS, hepatocyte urea cycle enzyme protein levels and mRNA levels of the urea cycle enzyme genes in pair-fed rats. In addition, serum acute phase proteins and their liver mRNA levels were measured.


RESULTS
After TNF-α, CUNS and hepatocyte urea cycle enzyme protein expressions were unchanged while urea cycle enzyme mRNA levels decreased. Liver mRNA levels of α2MG, haptoglobin and α1AGP rose and their serum levels increased equally.


CONCLUSIONS
Despite a fully established 24-h acute phase response, there was no change in the in vivo capacity for disposal of amino-N by urea synthesis or in the urea cycle enzyme proteins, although the expression of the urea cycle enzyme genes was decreased. Thus, in vivo urea synthesis was not orchestrated together with acute phase protein synthesis so as to limit N waste despite genetic regulation to this effect. This may contribute towards catabolism of inflammation.
Thomsen
Karen L
KL
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus C, Denmark. karethom@rm.dk
Aagaard
Niels K
NK
Nielsen
Susanne S
SS
Grønbaek
Henning
H
Jessen
Niels
N
Frystyk
Jan
J
Vilstrup
Hendrik
H
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism*
D000209:Acute-Phase Proteins; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014508:Urea