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Signaling Mechanisms of Apoptosis Resistance in Lymphoid Cells Exposed to Hyperosmotic Stress
Author(s) -
Scoltock Alyson Bell,
Bortner Carl,
Cidlowski John
Publication year - 2012
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.26.1_supplement.798.6
Subject(s) - apoptosis , protein kinase b , microbiology and biotechnology , osmotic shock , survivin , p38 mitogen activated protein kinases , mapk/erk pathway , signal transduction , caspase , biology , osmotic concentration , programmed cell death , chemistry , biochemistry , gene
Hyperosmotic stress is well known to induce apoptosis in T‐lymphocytes. We have now generated a lymphocyte cell line (OS 4–15) that is highly resistant to hyperosmotic stress when compared to the parental, S49 mouse t‐cell lymphoma cells. These cells are also resistant to other stimuli that trigger the intrinsic apoptotic pathway but not to activators of the extrinsic pathway. To delineate the mechanism of resistance in the OS 4–15 cells we studied the expression of the apoptosis proteins Bim, Bax, Bcl‐2, Bclx‐L, and survivin as well as caspases 8, 9 and 3. Little difference in the levels of these proteins was detected when compared to the parental cells. Since the OS 4–15 cells retain the ability to undergo apoptosis, we evaluated the initial signaling pathways activated by hyperosmotic stress in these cells. Hyperosmotic treatment resulted in p38 and JNK activation to a similar extent in both cell types, with no activation of ERK. In the parental cells, AKT was rapidly inactivated by hyperosmotic stress however AKT activity remained elevated in the OS 4–15 cells. Interestingly, inhibition of AKT activation sensitized the OS 4–15 cells to osmotic stress‐induced apoptosis. These data suggest that increased activation of AKT is at least partially responsible for the resistance to intrinsically induced apoptosis observed in the OS 4–15 cells.