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PMID:15897806

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Citation

Struck, J, Uhlein, M, Morgenthaler, NG, Fürst, W, Höflich, C, Bahrami, S, Bergmann, A, Volk, HD and Redl, H (2005) Release of the mitochondrial enzyme carbamoyl phosphate synthase under septic conditions. Shock 23:533-8

Abstract

To identify sepsis-related dysregulations of protein expression in the liver, we used a baboon model of acute endotoxemia and performed comparative proteome analysis. Treatment with lipopolysaccharide (LPS) was followed by an early but long-lasting (5-48 h) generation of N-terminal fragments of carbamoyl phosphate synthase-1 (CPS-1), an abundant enzyme of the hepatic urea cycle, which is normally located in the mitochondrial matrix. In addition, we developed a new sandwich immunoassay to determine circulating CPS-1 in human and baboons. We found CPS-1 to be induced by LPS and to be released into the circulation of healthy humans and baboons as early as 4 to 5 h after stimulation. Similarly, CPS-1 levels increased after injection of gram-positive bacteria in another baboon model. Enhanced CPS-1 levels were also detected in serum of patients with sepsis. Our data demonstrate fragmentation of CPS-1 in the liver and early increase in circulating CPS-1 levels under septic conditions. We suggest that circulating CPS-1 might serve as a novel serum marker indicating mitochondrial impairment of the liver and/or the small intestine in critically ill patients.

Links

PubMed

Keywords

Animals; Arginine/metabolism; Bilirubin/metabolism; Blotting, Western; Carbamoyl-Phosphate Synthase (Ammonia)/chemistry; Carbamoyl-Phosphate Synthase (Ammonia)/metabolism; Electrophoresis, Gel, Two-Dimensional; Endotoxins/metabolism; Humans; Immunoassay; Intestine, Small/pathology; Kinetics; Lipopolysaccharides/metabolism; Liver/metabolism; Liver/pathology; Mass Spectrometry; Mitochondria/enzymology; Mitochondria/metabolism; Mitochondria/pathology; Papio; Peptides/chemistry; Protein Structure, Tertiary; Proteomics; Sepsis/enzymology; Sepsis/metabolism; Subcellular Fractions/metabolism; Submitochondrial Particles/metabolism; Time Factors; Urea/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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