[Biopterin synthesis and GTP cyclohydrolase I mRNA expression in rats following endotoxic shock].
OBJECTIVE
To investigate the potential role of changes in biopterin (tetrahydrobiopterin and more oxidized species) synthesis and GTP cyclohydrolase I (GTP-CHI) mRNA expression in endotoxic shock.


METHODS
SD rats were subjected to endotoxic shock by a bolus injection of lipopolysaccharide (15 mg/kg, i.p.), biopterin and GTP-CHI mRNA levels in liver, kidney, and intestine were determined at 4, 8 hours following endotoxin challenge.


RESULTS
Tissue biopterin levels significantly elevated in liver, kidney, and intestine, with high levels sustaining for 8 hours after endotoxin challenge (P < 0.05, P < 0.01). Similarly, GTP-CHI mRNA induction in various tissues substantially increased within 4 hours compared to normal controls (P < 0.05, P < 0.01). It was also shown that hepatic and renal biopterin levels were positively correlated with glutamic pyruvic transaminase (GPT) and also blood urea nitrogen (BUN) values (both P < 0.01). In addition, treatment with recombinant bactericidal/permeability increasing protein (rBPI(21)) markedly reduced tissue biopterin and GTP-CHI mRNA levels, concomitant with significant decreases in GPT, BUN as well as D-lactate values.


CONCLUSIONS
Biopterin synthesis and release may be involved in the development of endotoxin-induced multiple organ dysfunction, and early use of rBPI(21) is effective to inhibit marked GTP-CHI mRNA expression and biopterin formation following septic shock.
Yao
Y
Y
Trauma Research Center, 304th Hospital, People's Liberation Army, Beijing 100037.
Zhao
X
X
Yu
Y
Y
Sheng
Z
Z
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001708:Biopterins / Q000096:biosynthesis*; D001798:Blood Proteins / Q000494:pharmacology; D006136:GTP Cyclohydrolase / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C021623:bactericidal permeability increasing protein; D001708:Biopterins; D006136:GTP Cyclohydrolase