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Science 21 February 1997:
Vol. 275. no. 5303, pp. 1129 - 1132
DOI: 10.1126/science.275.5303.1129
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Reports

Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked

Jie Yang, Xuesong Liu, * Kapil Bhalla, Caryn Naekyung Kim, Ana Maria Ibrado, Jiyang Cai, Tsung-I Peng, Dean P. Jones, Xiaodong Wang *dagger

Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a variety of stimuli. Cytosolic cytochrome c is necessary for the initiation of the apoptotic program, suggesting a possible connection between Bcl-2 and cytochrome c, which is normally located in the mitochondrial intermembrane space. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria. Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria.

J. Yang, X. Liu, C. N. Kim, J. Cai, D. P. Jones, X. Wang, Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
K. Bhalla and A. Ibrado, Division of Hematology-Oncology, Department of Medicine, Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
T.-I Peng, Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
*   Present address: Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, USA.

dagger    To whom correspondence should be addressed.

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In vitro and In vivo Antitumor Effects of the Dual Insulin-Like Growth Factor-I/Insulin Receptor Inhibitor, BMS-554417.
P. Haluska, J. M. Carboni, D. A. Loegering, F. Y. Lee, M. Wittman, M. G. Saulnier, D. B. Frennesson, K. R. Kalli, C. A. Conover, R. M. Attar, et al. (2006)
Cancer Res. 66, 362-371
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Flavopiridol and Histone Deacetylase Inhibitors Promote Mitochondrial Injury and Cell Death in Human Leukemia Cells That Overexpress Bcl-2.
G. Dasmahapatra, J. A. Almenara, and S. Grant (2006)
Mol. Pharmacol. 69, 288-298
   Abstract »    Full Text »    PDF »
Gold(III) Porphyrin 1a Induced Apoptosis by Mitochondrial Death Pathways Related to Reactive Oxygen Species.
Y. Wang, Q.-Y. He, R. W.-Y. Sun, C.-M. Che, and J.-F. Chiu (2005)
Cancer Res. 65, 11553-11564
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E2 of Hepatitis C Virus Inhibits Apoptosis.
S. H. Lee, Y. K. Kim, C. S. Kim, S. K. Seol, J. Kim, S. Cho, Y. L. Song, R. Bartenschlager, and S. K. Jang (2005)
J. Immunol. 175, 8226-8235
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Reactive oxygen species production by mitochondria in endothelial cells exposed to reoxygenation after hypoxia and glucose depletion is mediated by ceramide.
S. Therade-Matharan, E. Laemmel, S. Carpentier, Y. Obata, T. Levade, J. Duranteau, and E. Vicaut (2005)
Am J Physiol Regulatory Integrative Comp Physiol 289, R1756-R1762
   Abstract »    Full Text »    PDF »
Orally Administered Green Tea Polyphenols Prevent Ultraviolet Radiation-Induced Skin Cancer in Mice through Activation of Cytotoxic T Cells and Inhibition of Angiogenesis in Tumors.
S. K. Mantena, S. M. Meeran, C. A. Elmets, and S. K. Katiyar (2005)
J. Nutr. 135, 2871-2877
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Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2.
J. Zhu, L. Xiong, B. Yu, and J. Wu (2005)
Mol. Pharmacol. 68, 1831-1838
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(R)-{alpha}-Lipoic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Damage.
L. A. Voloboueva, J. Liu, J. H. Suh, B. N. Ames, and S. S. Miller (2005)
Invest. Ophthalmol. Vis. Sci. 46, 4302-4310
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Hepatocyte Growth Factor Protects RPE Cells from Apoptosis Induced by Glutathione Depletion.
M. Jin, J. Yaung, R. Kannan, S. He, S. J. Ryan, and D. R. Hinton (2005)
Invest. Ophthalmol. Vis. Sci. 46, 4311-4319
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Loss of BCL-2 in the progression of oral cancer is not attributable to mutations.
L L Loro, A C Johannessen, and O K Vintermyr (2005)
J. Clin. Pathol. 58, 1157-1162
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pH-dependent Interaction of Cytochrome c with Mitochondrial Mimetic Membranes: THE ROLE OF AN ARRAY OF POSITIVELY CHARGED AMINO ACIDS.
C. Kawai, F. M. Prado, G. L. C. Nunes, P. Di Mascio, A. M. Carmona-Ribeiro, and I. L. Nantes (2005)
J. Biol. Chem. 280, 34709-34717
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Oxidative and nitrosative stress in brain mitochondria of diabetic rats.
R Mastrocola, F Restivo, I Vercellinatto, O Danni, E Brignardello, M Aragno, and G Boccuzzi (2005)
J. Endocrinol. 187, 37-44
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Epstein-Barr Virus-Encoded Poly(A)- RNA Confers Resistance to Apoptosis Mediated through Fas by Blocking the PKR Pathway in Human Epithelial Intestine 407 Cells.
A. Nanbo, H. Yoshiyama, and K. Takada (2005)
J. Virol. 79, 12280-12285
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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.
A. Barrier, N. Olaya, F. Chiappini, F. Roser, O. Scatton, C. Artus, B. Franc, S. Dudoit, A. Flahault, B. Debuire, et al. (2005)
FASEB J 19, 1617-1626
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Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells.
J.-C. Lee, C.-H. Lee, C.-L. Su, C.-W. Huang, H.-S. Liu, C.-N. Lin, and S.-J. Won (2005)
Carcinogenesis 26, 1716-1730
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Bcl-2 Antisense Oligonucleotide Overcomes Resistance to E1A Gene Therapy in a Low HER2-Expressing Ovarian Cancer Xenograft Model.
C. Bartholomeusz, H. Itamochi, L. X.H. Yuan, F. J. Esteva, C. G. Wood, N. Terakawa, M.-C. Hung, and N. T. Ueno (2005)
Cancer Res. 65, 8406-8413
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SOD2 Protects against Oxidation-Induced Apoptosis in Mouse Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration.
E. Kasahara, L.-R. Lin, Y.-S. Ho, and V. N. Reddy (2005)
Invest. Ophthalmol. Vis. Sci. 46, 3426-3434
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Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats.
D. K. Jagadeesha, T. E. Lindley, J. DeLeon, R. V. Sharma, F. Miller, and R. C. Bhalla (2005)
Am J Physiol Heart Circ Physiol 289, H1047-H1053
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