Glutamine: the first clinically relevant pharmacological regulator of heat shock protein expression?
OBJECTIVE
It is well known that enhanced heat shock protein expression protects organisms against morbidity and mortality following experimental injury/illness. Presently, chemical/gene therapy based laboratory methods of enhancing heat shock protein expression are impractical for clinical application. Our laboratory has shown glutamine enhances heat shock protein expression following models of experimental illness/injury. The purpose of this review is to examine recent data supporting the use of glutamine as a clinically relevant enhancer of heat shock protein expression.


RESULTS
Recent studies indicate glutamine induces heat shock protein-70, HO-1 (heat shock protein-32), and heat shock protein-27 in models of illness/injury. Enhanced expression of heat shock proteins correlates with improved outcome in these models. Further, in-vitro data reveal glutamine enhances DNA binding of heat shock factor-1 (heat shock protein transcription factor) to its promoter. Finally, recently published pilot data show that glutamine enhances serum heat shock protein-70 expression in critically ill patients and this enhanced expression correlates with improved outcome.


CONCLUSIONS
Currently, extensive data support glutamine as a gene level regulator of heat shock protein expression. Glutamine depletion, following critical illness/injury, is likely to lead to a state in which organisms are unable to induce heat shock proteins appropriately. Further, pharmacologic supplementation of glutamine potentiates the heat shock protein response prior to and following a stress. Pharmacologic trials utilizing glutamine to enhance heat shock proteins in humans are indicated.
Wischmeyer
Paul E
PE
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Paul.Wischmeyer@UCHSC.edu
D000818:Animals; D016638:Critical Illness; D005786:Gene Expression Regulation; D005973:Glutamine / Q000378:metabolism* / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology
D006360:Heat-Shock Proteins; D005973:Glutamine