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Acute L ‐glutamine deprivation compromises VEGF‐a upregulation in A549/8 human carcinoma cells
Author(s) -
Drogat Benjamin,
Bouchecareilh Marion,
North Sophie,
Petibois Cyril,
Déléris Gérard,
Chevet Eric,
Bikfalvi Andréas,
Moenner Michel
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21044
Subject(s) - glutamine , downregulation and upregulation , angiogenesis , hypoxia (environmental) , apoptosis , biology , glutamine synthetase , endocrinology , cancer research , medicine , chemistry , biochemistry , amino acid , organic chemistry , oxygen , gene
Tumor ischemia participates in angiogenesis and cancer progression through cellular responses to hypoxia and nutrient deprivation. However, the contribution of amino acids limitation to this process remains poorly understood. Using serum‐free cell culture conditions, we tested the impact of L ‐glutamine deprivation on metabolic and angiogenic responses in A549/8 carcinoma cells. In these cells, lowering glutamine concentration modified the cell cycle distribution and significantly induced apoptosis/necrosis. Although glutamine deprivation led to a HIF‐independent increase in VEGF‐A mRNA, the corresponding protein level remained low and correlated with the inhibition of protein synthesis and activation of the GCN2/eIF2α pathway. Limitation of glutamine availability also hampers hypoxia‐ and hypoglycemia‐induced VEGF‐A protein upregulation. Thus, glutamine deprivation may have no direct effect on VEGF‐dependent angiogenesis, compared to hypoxia or to glucose deprivation, and may instead be detrimental to cancer progression by antagonizing ischemia‐induced stresses. J. Cell. Physiol. 212: 463–472, 2007. © 2007 Wiley‐Liss, Inc.