Roles of cytoplasmic ca2& and intracellular ca2& stores in
induction and suppression of apoptosis in s49 cells.
Bian, Xiaopeng, Francis M. Hughes, Jr., Yi Huang, John A. Cidlowski,
James W. Putney, Jr.
Laboratory of Cellular and Molecular Pharmacology, National
Institute of Environmental Health Sciences, National Institutes of
Health, Research Triangle Park, North Carolina 27709
APStracts 3:0368C, 1996.
The Ca2&-ATPase inhibitors, thapsigargin and cyclopiazonic acid,
depleted intracellular Ca2& stores, induced large increases in
[Ca2&]i, and caused apoptosis in S49 cells. Removal of
extracellular Ca2& augmented apoptosis due to thapsigargin,
indicating that depletion of Ca2& from intracellular stores is
responsible for apoptosis with this agent. Overexpression of the
apoptosis suppressor, Bcl-2, inhibited apoptosis due to thapsigargin,
but did not affect thapsigargin-induced Ca2& signalling.
Dexamethasone induced apoptosis, diminished the size of the
endoplasmic reticulum Ca2& pool, and caused a small elevation of
intracellular Ca2&. However, this elevation was not due to
Ca2& influx because the increase was similar in the presence or
absence of Ca2& in the medium. Furthermore, in contrast to the
results with thapsigargin, apoptosis due to dexamethasone was
unchanged in a Ca2&-free medium. These results indicate that
depletion of Ca2& stores initiates a pathway leading to
apoptosis. Elevations in cytoplasmic Ca2& appears to play a
lesser role than previously thought in the actions of Bcl-2 and
glucocorticoids.
Received 6 June 1996; accepted in final form 19 November 1996.
APS Manuscript Number C317-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996