• Kristen D Singleton, Natalie Serkova, Anirban Banerjee, Xianzhong Meng, Fabia Gamboni-Robertson, and Paul E Wischmeyer.
• Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
• Nutrition. 2005 Feb 1; 21 (2): 214-23.

ObjectiveSeptic shock leads to derangement of cellular metabolism. Enhanced heat shock protein 70 (HSP-70) can preserve cellular metabolism after other forms of cellular stress. Glutamine (GLN) can enhance lung HSP-70 expression after lethal endotoxemia. However, it is unknown whether GLN can enhance HSP-70 expression and attenuate lung metabolic dysfunction after sublethal endotoxemia. Our aim was to determine whether GLN could upregulate HSP-70 and attenuate metabolic dysfunction in lung tissue after sublethal endotoxemia.MethodsSprague-Dawley rats were assigned to one of five groups. The first two groups were treated with Escherichia coli lipopolysaccharide (LPS; 1 mg/kg intravenously). GLN (0.75 g/kg intravenously) or balanced salt solution as a control was administered 5 min after LPS administration. The next two groups of rats were treated with quercetin (HSP-70 inhibitor; 400 mg/kg intraperitoneally) 6 h before LPS administration. The final group received no treatment. Lung tissue was harvested 24-h after LPS and analyzed with immunofluorescence and western blot for HSP-70. Tissue metabolites were quantified by 1H and 31P nuclear magnetic resonance spectroscopy.ResultsGLN compared with balanced salt solution (BSS) administration in LPS-treated animals led to significant increases in lung HSP-70. Increased HSP-70 expression was observed in lung epithelial cells and macrophages. GLN significantly improved the ratio of adenosine triphosphate to adenosine diphosphate in the lung after LPS. Quercetin inhibited a GLN-mediated increase in lung HSP-70 and blocked a beneficial effect of GLN on the ratio of adenosine triphosphate to adenosine diphosphate after LPS.ConclusionsA single dose of GLN can enhance HSP-70 in pulmonary epithelial cells and macrophages after sublethal endotoxemia. Further, GLN can attenuate endotoxin-induced lung metabolic dysfunction. GLN's beneficial effect on lung tissue after metabolic dysfunction caused by sublethal endotoxemia may be mediated in part by enhanced HSP-70.

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