Oehler Rudolf, Pusch Erich, Dungel Peter, Zellner Maria, Eliasen Maja Munk, Brabec Marianne, Roth Erich
Surgical Research Laboratories, University of Vienna, Austria.
Br J Nutr. 2002 Jan;87 Suppl 1:S17-21. doi: 10.1079/bjn2001453.
During sepsis and major trauma the blood glutamine (Gln) level is reduced. The administration of Gln can improve the outcome of these patients. However, the mechanism of this beneficial effect of Gln is poorly understood. In the course of critical illness leucocytes are confronted with cytotoxic inflammatory mediators. To protect themselves against these factors, cells express heat shock proteins (HSP). Previous studies have shown that the expression of the major inducible HSP (HSP70) is improved by high Gln concentrations above 4 mM. In this study we investigated whether Gln depletion, such as observed during critical illness, has an effect on HSP70 expression. Human lymphocytes exposed for 2 h to 42 degrees C showed a 3-fold increase in HSP70 expression (P<0.01). A preceding Gln starvation period over 3 days had no influence on this increase. However, when Gln is reduced during the stress response, HSP70 expression is impaired. A reduction of Gln from 0.5 mM (physiological) to 0.125 mM (pathological) led to a 40% lower HSP70 level (P<0.002). In contrast, increasing Gln concentrations (up to 2 mM) had only minor stimulatory effects (about 15%). This Gln-dependency of heat mediated HSP70 expression was observed in resting as well as proliferating lymphocytes. Our data indicate that during periods of reduced plasma Gln levels the stress response of human lymphocytes is impaired. Thus, Gln may be essential to minimize the susceptibility of leucocytes to cytotoxic inflammatory mediators. This is a new aspect of the protective effect of Gln supplementation in critically ill patients.
在脓毒症和严重创伤期间，血液中的谷氨酰胺（Gln）水平会降低。给予谷氨酰胺可改善这些患者的预后。然而，谷氨酰胺这种有益作用的机制尚不清楚。在危重病过程中，白细胞会接触到具有细胞毒性的炎症介质。为了保护自身免受这些因素的影响，细胞会表达热休克蛋白（HSP）。先前的研究表明，高于4 mM的高谷氨酰胺浓度可改善主要诱导型热休克蛋白（HSP70）的表达。在本研究中，我们调查了危重病期间观察到的谷氨酰胺耗竭是否对HSP70表达有影响。人淋巴细胞在42摄氏度下暴露2小时后，HSP70表达增加了3倍（P<0.01）。提前3天的谷氨酰胺饥饿期对这种增加没有影响。然而，当在应激反应期间谷氨酰胺减少时，HSP70表达会受损。谷氨酰胺从0.5 mM（生理水平）降至0.125 mM（病理水平）会导致HSP70水平降低40%（P<0.002）。相比之下，增加谷氨酰胺浓度（高达2 mM）只有轻微的刺激作用（约15%）。在静息和增殖的淋巴细胞中均观察到热介导的HSP70表达对谷氨酰胺的这种依赖性。我们的数据表明，在血浆谷氨酰胺水平降低期间，人淋巴细胞的应激反应受损。因此，谷氨酰胺对于将白细胞对细胞毒性炎症介质的易感性降至最低可能至关重要。这是补充谷氨酰胺对危重病患者保护作用的一个新方面。
