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Inhibition Of Na+/K+‐ATPase By Ouabain Potentiates Apoptosis By Inducing Pertubations In Cell Calcium Homeostasis: A Protective Role Selective For Bcl‐2
Author(s) -
Panagiotidis Michail,
Cidlowski John A
Publication year - 2006
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.20.4.a119-b
Subject(s) - ouabain , microbiology and biotechnology , apoptosis , jurkat cells , thapsigargin , chemistry , fas ligand , calcium metabolism , calcium , programmed cell death , biology , biochemistry , intracellular , immunology , sodium , organic chemistry , immune system , t cell
Apoptosis is a well‐defined programmed process with distinctive characteristics including cellular shrinking, chromatin condensation, and formation of membrane‐bound apoptotic bodies. Cell shrinkage occurs early in apoptosis and is accompanied by changes in the activity of ion channels and plasma membrane transporters. The Na + /K + ‐ATPase couples the energy released from the hydrolysis of ATP to the transport of Na + and K + ions thus controlling cell volume and plasma membrane potential. Additionally, the Na + /K + ‐ATPase is the only known receptor for cardiac glycosides including ouabain. We hypothesize that the Na + /K + ‐ATPase is essential in modulating apoptosis and thus its inhibition with ouabain should potentiate the apoptotic process. We report that ouabain potentiated apoptosis in wild‐type Jurkat cells exposed to Fas Ligand (FasL) by increasing % of cells with degraded DNA content and increased caspase 3/7‐like activity. When cells were treated with ouabain and then exposed to other apoptotic agents (H 2 O 2 , staurosporine, TRAIL, thapsigargin) only exposure to TRAIL showed potentiation of apoptosis indicating that such potentiation is restricted to the death receptor pathway (FasL and TRAIL). In addition, we observed that ouabain induced perturbations in cell calcium homeostasis upon both FasL and TRAIL treatments. Ouabain‐induced potentiation of apoptosis was abolished in Bcl‐2 overexpressing cells by inhibiting perturbations in cell calcium homeostasis whereas Bcl‐X L overexpression had no effect. To conclude, our data indicate a novel role for calcium in modulating ouabain‐induced potentiation of apoptosis and that Bcl‐2 selectively modulates calcium homeostasis.