Premium
p38 Stress Kinase Controls Late Apoptotic Events in L‐Glutamine‐deprived Sp2/0‐Ag14 Murine Hybridoma Cells
Author(s) -
Harnett Curtis C.,
Furtak Teresa,
Guerin Paul,
Gauthier Eric R.
Publication year - 2007
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.21.6.a1042-d
Subject(s) - apoptosis , p38 mitogen activated protein kinases , programmed cell death , glutamine , microbiology and biotechnology , oxidative stress , mitochondrion , caspase 3 , kinase , biology , caspase , protein kinase a , biochemistry , amino acid
L‐Glutamine (Gln) starvation triggers apoptosis in Sp2/0‐Ag14 (Sp2/0) murine hybridoma cells within 1 hour. Here we report on the role of p38, a stress‐signalling kinase, in this phenomenon. p38 activation occurred after key events necessary for commitment to apoptosis, such as caspase‐3 activation and mitochondrial dysfunction. Furthermore, inhibition of p38 with SB203580 prior to Gln starvation did not prevent caspase activation. On the other hand, SB203580 treatment reduced both nuclear condensation and apoptotic body formation, implicating p38 in modulating late apoptotic events. Gln withdrawal‐induced caspase activation and cell death were inhibited by Bcl‐xL overexpression or by pre‐incubation with Z‐VAD‐fmk. Interestingly, p38 activity was inhibited in Bcl‐xL expressing cells, but not by Z‐VAD‐fmk treatment, indicating that p38 activation is downstream of the mitochondria but independent of caspase activation. Moreover, N‐acetyl‐cysteine prevented p38 phosphorylation, indicating that p38 activation is triggered by an oxidative stress. Altogether, our findings indicate that p38 does not contribute to the induction of cell death in Gln starved Sp2/0 cells. Rather, Gln withdrawal leads to mitochondrial dysfunction, resulting in an oxidative stress and p38 activation. Activated p38 would then promote late apoptotic events. Research supported by NSERC‐Canada.