Changes of plasma glutamine concentration and hepatocyte membrane system N transporters expression in early endotoxemia.

BACKGROUND:Glutamine plays important roles in health and critical illness. During endotoxemia, glutamine metabolism, including its plasma level and transport, changes markedly. Previous studies have demonstrated that system N transporters in hepatocytes play a major role in hepatic glutamine transport. However, little is known about the changes of mRNA and protein expression of system N transporters in hepatocyte plasma membrane. Furthermore, the alteration of plasma glutamine concentration during endotoxemia is still controversial. In this study, we investigated the changes in early endotoxemic rats by intraperitoneal injection of lipopolysaccharide (LPS). MATERIALS AND METHODS:Three, 6, 12 mg/kg body weight doses of LPS were injected intraperitoneally to establish the endotoxemic rat model; equal volume of 0.9% saline was used as the control. Before and 2, 4, 6, 12, 24h after injections, plasma glutamine concentration, mRNA, and protein expression of SNAT3 and SNAT5 transporters in hepatocyte plasma membrane were detected by high performance liquid chromatography, real-time PCR, and Western blot, respectively. RESULTS:LPS injection resulted in a marked increase of the plasma glutamine concentration from 4 to 12h (3mg/kg) and 2 to 6h (6 mg/kg, 12 mg/kg) after the injection compared with its physiologic level, and a significant decrease in 6, 12 mg/kg groups at 24h. Both the mRNA and protein expression of SNAT3 and SNAT5 were enhanced by LPS in a time- and dose-dependent manner. CONCLUSIONS:The plasma glutamine concentration in endotoxemic rat increased transiently during early endotoxemia but subsequently decreased over time. The effect of LPS on system N expression occurs not only at the protein level, but also at the mRNA level. It is reasonable to supplement glutamine for patients with sepsis or endotoxemia begin at 6 to 12h after the development of disease.

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