Abstract
The objective of this study was to examine whether and how TNF-α affects glutamine-enhanced protein synthesis and the expression of the amino acid transporter ASCT2 in the small intestine at the mRNA and protein levels. A total of 30 male Sprague-Dawley rats were randomly assigned into three groups, namely the total parenteral nutrition (TPN; control), glutamine-treated (Gln), and glutamine- and tumor necrosis factor-α (TNF-α)-treated (TNF-α) groups. At 30 min prior to examination, all rats were mainlined with [L-15N]leucine. The concentration of TNF-α in plasma and of glutamine in plasma and the small intestine was measured. The fractional synthesis rate (FSR) of protein and the mRNA and protein expression levels of ASCT2 in the small intestine were assessed. The level of TNF-α was highest in the TNF-α group and the glutamine concentration was elevated to a greater extent in the TNF-α group than in the other two groups. However, the FSR of protein in the small intestine was significantly higher in the Gln group compared with that in the TNF-α group. The mRNA and protein expression levels of ASCT2 in the experimental groups were significantly higher that those in the control group, but did not differ significantly between the Gln and TNF-α groups. These results indicate that TNF-α may attenuate glutamine-stimulated protein synthesis in the small intestine in the early stage of sepsis in rats. The mechanism may be that TNF-α inhibits the function of the glutamine transporter in the uptake the glutamine into target cells for protein synthesis. This inhibition may occur at or following protein translation.
Highlights
Sepsis is the leading cause of mortality in intensive care units around the world [1]
As the aim of this study was to investigate whether tumor necrosis factor‐α (TNF‐α) inhibits the regulatory effect of glutamine on protein synthesis in the small intestine, it was first tested whether glutamine stimulated protein synthesis in the small intestine and whether this stimulation was attenuated by TNF‐α was examined
The plasma glutamine level was lowest in the total parenteral nutrition (TPN) group, and increased markedly following treatment with glutamine and TNF‐α, and was the highest in the TNF‐α group
Summary
Sepsis is the leading cause of mortality in intensive care units around the world [1]. The correct diagnosis and treatment of sepsis is complicated, but must be conducted quickly since a delayed approach increases the risk of mortality. Low plasma glutamine concentration is associated with poor clinical outcome and increased risk of mortality [5]. Studies have demonstrated that glutamine can effectively attenuate the rapid progression of sepsis that leads to multiple organ failure and eventually mortality [4,6,7,8,9,10,11]. Certain studies have disclosed that the effect of glutamine is not ideal in sepsis, especially in the early stage [12,13,14]
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