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Modulation of late apoptotic events by ammonia in glutaminedeprived mouse hybridoma cells
Author(s) -
Gauthier Eric R.,
Abusneina Abdelmuhsen
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.793.5
Subject(s) - azaserine , apoptosis , glutamine , dna fragmentation , fragmentation (computing) , ammonium , ammonium chloride , chemistry , glutaminolysis , biochemistry , biology , programmed cell death , microbiology and biotechnology , amino acid , ecology , organic chemistry
Highly proliferating cells reprogram their metabolism in order to fulfill their requirements in biosynthetic precursors. One consequence of this metabolic adaptation is glutamine (Gln) addiction, a phenomenon whereby cells become dependent on Gln for their survival. Using Sp2/0‐Ag14 (Sp2/0) hybridoma cells, we examined the effect of ammonium ions, a product of glutaminolysis, on the viability of Gln‐deprived cells. Supplementing Gln‐deprived Sp2/0 cells with 5 mM ammonium acetate (NH 4 + acetate) or 5 mM ammonium chloride (NH 4 + chloride) resulted in a significant increase in cell viability. Both ammonium salts also protected Sp2/0 cells treated with the toxic Gln analog azaserine. Supplementing Gln‐starved Sp2/0 cells with either ammonium salt did not alter cytosolic cytochrome c release or caspase‐3 activation, indicating that the mechanisms triggering the apoptotic machinery remained intact. Interestingly, a significant reduction in the number of cells with apoptotic nuclear condensation and fragmentation was observed. However, neither NH 4 + acetate nor NH 4 + chloride interfered with DNA fragmentation and nuclear lamin A/C cleavage, two key events observed in apoptotic nuclear condensation and fragmentation. All together, these data suggest that the pro‐survival effect of ammonium salts are linked with an inhibition of late apoptotic events. Funded by NSERC‐CANADA (to ERG).