Stressing out over survival: glutamine as an apoptotic modulator.

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Fuchs BC, Bode BP

Stressing out over survival: glutamine as an apoptotic modulator.

J Surg Res. 2006 Mar;131(1):26-40. Epub 2005 Sep 8.

PubMed ID

16154153 [ View in PubMed

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Abstract

INTRODUCTION: The amino acid glutamine (GLN) has received considerable attention as a potential therapeutic adjuvant in critical illness and in improving postoperative clinical outcomes. Most studies on the role of GLN in cellular physiology have historically focused on its anabolic roles in specific cell types and its contribution to growth in cancer cells. However, an emerging body of work that examines the consequences of GLN deprivation on cellular survival and gene expression has constructed a new paradigm for this amino acid, namely, that limited extracellular GLN supplies modulate stress and apoptotic responses. METHODS: A survey of the scientific literature was conducted on GLN in cell survival signaling and apoptosis. Work from our laboratory in liver cancer cells also was included in this review. RESULTS: Most studies on this topic have used mammalian cell lines derived from the gut, immune system (including hybridomas), and various cancers. GLN limitation, even in the presence of an adequate glucose supply, impacts stress-related gene expression, differentially modulates receptor-mediated apoptosis, and directly elicits apoptosis through signaling mechanisms and caspase cascades that are specific to cell type. To date, GLN transporters, cellular hydration, glutaminyl-tRNA synthetase, ATP levels, mRNA stability, and glutathione economy have been variably implicated in GLN-dependent survival signaling. CONCLUSION: The cell type-specific mechanisms underlying the regulatory role of GLN in cell survival continue to unfold at a steady pace through in vitro studies. These results have collectively provided testable hypotheses for further in vivo studies into their physiological relevance during GLN "nutritional pharmacology."

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
L-Glutamine	Glutamine--tRNA ligase	Protein	Humans	Unknown	Substrate	Details