| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, May 9, 1996, and in revised form, November 7, 1996)
From the We have investigated cell metabolism during
apoptosis in the murine interleukin-3 (IL-3)-dependent cell
line Bo and two derivative clones (B14 and B15) overexpressing human
bcl-2a. On removal of IL-3, Bo cells underwent apoptosis
within 8 h, whereas B14 and B15 cells were resistant for at least
24 h. Metabolically, Bo, B14, and B15 cells were indistinguishable
from each other. All were insensitive to mitochondrial poisons, derived
ATP entirely by glycolysis, and maintained similar mitochondrial
membrane potentials measured by rhodamine-123 fluorescence with or
without IL-3. All virtually ceased glycolysis and production of lactic
acid on IL-3 withdrawal but maintained intracellular [ATP] until in
Bo cultures the cells began to apoptose. B14 and B15 cells became
glycolytically arrested but maintained stable ATP levels during
protection from apoptosis. Depletion of intracellular ATP by uncoupling
the mitochondrial ATPase with 2,4-dinitrophenol or carbonyl cyanide
p-trifluoromethoxyphenylhydrazone induced apoptosis in Bo
cells with or without IL-3, but not in B14 or B15 cells.
bcl-2-overexpressing cells were recoverable with high
plating efficiency even after prolonged exposure to 2,4-dinitrophenol.
We conclude that IL-3 withdrawal leads to arrest of energy metabolism
in which ATP levels are maintained. In Bo cells this is followed by
apoptosis, whereas in bcl-2-overexpressing cells this state
is stably prolonged. ATP depletion is a strong apoptotic signal which
overrides IL-3 signaling in normal cells but is ineffective in
bcl-2-overexpressing cells. Prolonged metabolic arrest and
resistance to ATP depletion facilitated by bcl-2 are both
reversible. Persistent reversible metabolic dormancy would provide
cells with a survival advantage in nonsustainable environments (e.g. hypoxia or substrate lack) and suggests a mechanism
for the survival advantage displayed by cells overexpressing
bcl-2.
Volume 272, Number 8,
Issue of February 21, 1997
pp. 4680-4688
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
bcl-2 PROMOTES SURVIVAL IN HEMATOPOIETIC CELLS
INDUCED TO APOPTOSE BY GROWTH FACTOR WITHDRAWAL BY STABILIZING A FORM
OF METABOLIC ARREST
and
Exeter University Clinical Science
Institute,
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  F. J. Dufort, B. F. Bleiman, M. R. Gumina, D. Blair, D. J. Wagner, M. F. Roberts, Y. Abu-Amer, and T. C. Chiles Cutting Edge: IL-4-Mediated Protection of Primary B Lymphocytes from Apoptosis via Stat6-Dependent Regulation of Glycolytic Metabolism J. Immunol., October 15, 2007; 179(8): 4953 - 4957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vendrame, M. Segni, D. Grassetti, V. Tellone, G. Augello, V. Trischitta, M. Torlontano, and F. Dotta Impaired Caspase-3 Expression by Peripheral T Cells in Chronic Autoimmune Thyroiditis and in Autoimmune Polyendocrine Syndrome-2 J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5064 - 5068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Barrier, N. Olaya, F. Chiappini, F. Roser, O. Scatton, C. Artus, B. Franc, S. Dudoit, A. Flahault, B. Debuire, et al. Ischemic preconditioning modulates the expression of several genes, leading to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion FASEB J, October 1, 2005; 19(12): 1617 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Grazette, W. Boecker, T. Matsui, M. Semigran, T. L. Force, R. J. Hajjar, and A. Rosenzweig Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes: Implications for herceptin-induced cardiomyopathy J. Am. Coll. Cardiol., December 7, 2004; 44(11): 2231 - 2238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.L. Taylor, S.L. Weng, P. Fox, E.H. Duran, M.S. Morshedi, S. Oehninger, and S.J. Beebe Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality Mol. Hum. Reprod., November 1, 2004; 10(11): 825 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Imahashi, M. D. Schneider, C. Steenbergen, and E. Murphy Transgenic Expression of Bcl-2 Modulates Energy Metabolism, Prevents Cytosolic Acidification During Ischemia, and Reduces Ischemia/Reperfusion Injury Circ. Res., October 1, 2004; 95(7): 734 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tatsumi, J. Shiraishi, N. Keira, K. Akashi, A. Mano, S. Yamanaka, S. Matoba, S. Fushiki, H. Fliss, and M. Nakagawa Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes Cardiovasc Res, August 1, 2003; 59(2): 428 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Edinger and C. B. Thompson Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake Mol. Biol. Cell, July 1, 2002; 13(7): 2276 - 2288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Peralta, J. C. Perales, R. Bartrons, C. Mitchell, H. Gilgenkrantz, C. Xaus, N. Prats, L. Fernandez, E. Gelpi, J. Panes, et al. The Combination of Ischemic Preconditioning and Liver Bcl-2 Overexpression Is a Suitable Strategy to Prevent Liver and Lung Damage after Hepatic Ischemia-Reperfusion Am. J. Pathol., June 1, 2002; 160(6): 2111 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-W. Wang, J. B. Klein, and Y. J. Kang Metallothionein Inhibits Doxorubicin-Induced Mitochondrial Cytochrome c Release and Caspase-3 Activation in Cardiomyocytes J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 461 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gottlob, N. Majewski, S. Kennedy, E. Kandel, R. B. Robey, and N. Hay Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase Genes & Dev., June 1, 2001; 15(11): 1406 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chylicki, M. Ehinger, H. Svedberg, and U. Gullberg Characterization of the Molecular Mechanisms for p53-mediated Differentiation Cell Growth Differ., November 1, 2000; 11(11): 561 - 571. [Abstract] [Full Text]
|
|
|
|
|
|
C. Depre and H. Taegtmeyer Metabolic aspects of programmed cell survival and cell death in the heart Cardiovasc Res, February 1, 2000; 45(3): 538 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Aito, T. K. Aalto, and K. O. Raivio Correlation of oxidant-induced acute ATP depletion with delayed cell death in human neuroblastoma cells Am J Physiol Cell Physiol, November 1, 1999; 277(5): C878 - C883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Esposti, I. Hatzinisiriou, H. McLennan, and S. Ralph Bcl-2 and Mitochondrial Oxygen Radicals. NEW APPROACHES WITH REACTIVE OXYGEN SPECIES-SENSITIVE PROBES J. Biol. Chem., October 15, 1999; 274(42): 29831 - 29837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bialik, V. L. Cryns, A. Drincic, S. Miyata, A. L. Wollowick, A. Srinivasan, and R. N. Kitsis The Mitochondrial Apoptotic Pathway Is Activated by Serum and Glucose Deprivation in Cardiac Myocytes Circ. Res., September 3, 1999; 85(5): 403 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamada, T. Oligino, M. Mata, J. R. Goss, J. C. Glorioso, and D. J. Fink Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo PNAS, March 30, 1999; 96(7): 4078 - 4083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Chen, N. Takeyama, G. Brady, A. J.M. Watson, and C. Dive Blood Cells With Reduced Mitochondrial Membrane Potential and Cytosolic Cytochrome C Can Survive and Maintain Clonogenicity Given Appropriate Signals to Suppress Apoptosis Blood, December 15, 1998; 92(12): 4545 - 4553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yang, R. T. Matthews, J. B. Schulz, T. Klockgether, A. W. Liao, J.-C. Martinou, J. B. Penney Jr., B. T. Hyman, and M. F. Beal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride Neurotoxicity Is Attenuated in Mice Overexpressing Bcl-2 J. Neurosci., October 15, 1998; 18(20): 8145 - 8152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Garland and C. Rudin Cytochrome c Induces Caspase-Dependent Apoptosis in Intact Hematopoietic Cells and Overrides Apoptosis Suppression Mediated by bcl-2, Growth Factor Signaling, MAP-Kinase-Kinase, and Malignant Change Blood, August 15, 1998; 92(4): 1235 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-L. Mathieu, S. Gonin, Y. Leverrier, B. Blanquier, J. Thomas, C. Dantin, G. Martin, G. Baverel, and J. Marvel Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Protects against Interleukin-3 Starvation but Not DNA Damage-induced Apoptosis J. Biol. Chem., March 30, 2001; 276(14): 10935 - 10942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Vander Heiden, N. S. Chandel, X. X. Li, P. T. Schumacker, M. Colombini, and C. B. Thompson Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival PNAS, April 25, 2000; 97(9): 4666 - 4671. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
