Glutamine and heat shock protein expression

The most basic mechanism of cellular protection involves the expression of a highly conserved family of essential proteins, known as heat shock or stress proteins (HSPs). The expression of these proteins after a sublethal insult can induce stress tolerance and protect against a subsequent stress that otherwise would be lethal. Experimental data have shown that preinduction of the heat stress response can provide marked protection against many forms of cellular injury, including ischemia and reperfusion, lung injury, and shock. However, induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. Many researchers have found that glutamine (GLN), a conditionally essential amino acid, can enhance stress-induced HSP expression in vitro and improve cell survival against a variety of stressful stimuli. Further, recent data from me and my colleagues indicate that a single dose of intravenous GLN can enhance HSP expression, decrease end-organ injury, and enhance survival from septic shock in the intact rat. Thus GLN, which is beneficial in many settings of critical illness and injury, may be a clinically applicable enhancer of HSP expression. These results indicate that GLN could be used to enhance HSP expression and attenuate end-organ injury in situations when a major clinical stress is anticipated, such as before major surgical procedures (e.g., cardiac, vascular, and transplantation) or in the critically ill. (C) Elsevier Science Inc. 2002.