Document Detail

Glutamine-mediated attenuation of cellular metabolic dysfunction and cell death after injury is dependent on heat shock factor-1 expression.
MedLine Citation:
PMID:  16931604     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cellular metabolic dysfunction is associated with occurrence of multiple-organ failure after critical illness. Glutamine (GLN) attenuates cellular metabolic dysfunction in critical illness models. The mechanism of this protection is unclear. We previously demonstrated that GLN's benefit in critical illness might be due to enhanced heat shock protein (HSP) expression. We hypothesize that GLN's attenuation of cellular metabolic dysfunction is dependent on presence of heat shock factor-1 (HSF-1). METHODS: HSF-1 wild-type and knockout mouse embryonic fibroblasts (HSF-1+/+ and HSF-1-/-) were used in all experiments. Cells were not treated, or were treated with 8 mmol/L GLN and immediately exposed to heat stress injury (45 degrees C for 45 minutes). Cells were harvested for metabolic analysis by nuclear magnetic resonance (NMR) at 24 hours postinjury. Cell survival was assessed using the MTS assay. RESULTS: GLN treatment in HSF-1+/+ cells led to significant attenuation of decreases in adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratio, phosphomonoester/phosphodiester (PME/PDE) ratio, and cell survival observed in non-GLN-treated HSF-1+/+ cells. In HSF-1-/- cells, the beneficial effect of GLN on preservation of ATP/ADP ratio, PME/PDE proliferation, and cell survival was lost. GLN-treated HSF-1-/- cells had a significant increase in extracellular lactate concentrations vs GLN-treated HSF+/+ cells. CONCLUSIONS: GLN treatment attenuated cellular metabolic dysfunction and improved cell membrane recovery only in HSF-1+/+ cells. Cellular injury, as measured by lactate release and cell survival assay, was improved by GLN treatment in HSF-1+/+ cells alone. Thus, GLN's beneficial effect on cellular metabolic dysfunction and cell survival appears to be dependent on HSF-1 expression.
Zhi Yong Peng; Natalie J Serkova; Douglas J Kominsky; Jaimi L Brown; Paul E Wischmeyer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  JPEN. Journal of parenteral and enteral nutrition     Volume:  30     ISSN:  0148-6071     ISO Abbreviation:  JPEN J Parenter Enteral Nutr     Publication Date:    2006 Sep-Oct
Date Detail:
Created Date:  2006-08-25     Completed Date:  2006-12-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7804134     Medline TA:  JPEN J Parenter Enteral Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  373-8; discussion 379     Citation Subset:  IM    
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, 80262, USA.
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MeSH Terms
Apoptosis / drug effects*
Cell Survival / drug effects,  physiology
Cells, Cultured
Critical Illness / therapy
DNA-Binding Proteins
Dose-Response Relationship, Drug
Fibroblasts / drug effects*,  metabolism
Gene Expression
Gene Expression Regulation
Glutamine / pharmacology*
Heat-Shock Proteins / metabolism*
Heat-Shock Response / drug effects,  physiology*
Hot Temperature* / adverse effects
Magnetic Resonance Spectroscopy
Mice, Knockout
Random Allocation
Transcription Factors
Grant Support
K23 RR01379-01/RR/NCRR NIH HHS
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Heat-Shock Proteins; 0/Hsf1 protein, mouse; 0/Transcription Factors; 56-85-9/Glutamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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