Rapid induction of the intrinsic apoptotic pathway by L-glutamine starvation

Authors

  • Julie C. Paquette,

    1. Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada
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  • Paul J. Guérin,

    1. Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada
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  • Eric R. Gauthier

    Corresponding author
    1. Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada
    2. Department of Biology, Laurentian University, Sudbury, Ontario, Canada
    • Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ont., Canada P3E 2C6.
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Abstract

While the amino acid L-glutamine is known to play a role in the survival of several cell types, the underlying molecular mechanisms are still poorly defined. We show in this report that L-glutamine starvation rapidly triggered apoptosis in Sp2/0-Ag14 hybridoma cells. This process involved the activation of both caspases-9 and -3, suggesting that L-glutamine deprivation initiated an intrinsic apoptotic pathway in Sp2/0-Ag14 cells. Supporting this idea, the cytosolic release of the mitochondrial proteins SMAC/DIABLO and cytochrome c (Cyt c) was observed, with an initial limited leakage occurring during the first 30 min of L-glutamine deprivation, followed by a greater release after 60 min. The latter occurred simultaneously with the translocation of the pro-apoptotic protein Bax to the mitochondria. Finally, a decline in XIAP levels and the activation of caspases-3 and -9 were observed. Thus, L-glutamine deprivation of Sp2/0-Ag14 cells rapidly triggers intracellular events, which target the mitochondria, leading to the cytosolic release of apoptogenic factors, the activation of caspases-9 and -3, and the commitment to the death program. This work introduces the Sp2/0Ag14 hybridoma as a unique model for the study of the molecular events underlying the pro-survival function of L-glutamine. © 2004 Wiley-Liss, Inc.

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