| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
The First Department of Surgery [S. S., W. K., J. H., K. Y., H. M.], Department of Medical Genetics, Biomedical Research Center [S. S., Y. E., Y. T.], Osaka University Medical Schook, 2-2 Yamadaoka, Suita 565, Japan, and Department of Anatomy and Biology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki 569, Japan [Y. I., Y. O.]
The molecular mechanism of cell death due to hypoxia has not been elucidated. Our recent observations that overexpression of the anti-apoptotic proto-oncogene bcl-2 and a bcl-2-related gene, bcl-x, prevents hypoxic cell death suggest that hypoxia induces apoptosis. Using electron microscopy and confocal and nonconfocal fluorescence microscopy, we show here that hypoxia does, in fact, induce both necrosis and apoptosis, and that the proportion of these two modes is highly dependent on the cell type. Overexpression of Bcl-2 or Bcl-XL blocks hypoxia-induced apoptosis in a dose-dependent manner.
1 This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, of Japan.
2 To whom requests for reprints should be addressed. Phone: 81-6-879-3153; Fax: 81-6-879-3159.
Received 12/ 7/95. Accepted 3/ 4/96.
This article has been cited by other articles:
|
|
 |
|
  K. J. Svensson, J. E. Welch, P. Kucharzewska, P. Bengtson, M. Bjurberg, S. Pahlman, G. B. Ten Dam, L. Persson, and M. Belting Hypoxia-Mediated Induction of the Polyamine System Provides Opportunities for Tumor Growth Inhibition by Combined Targeting of Vascular Endothelial Growth Factor and Ornithine Decarboxylase Cancer Res., November 15, 2008; 68(22): 9291 - 9301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Priego, F. Feddi, P. Ferrer, S. Mena, M. Benlloch, A. Ortega, J. Carretero, E. Obrador, M. Asensi, and J. M. Estrela Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2- and superoxide dismutase 2-dependent mechanism Mol. Cancer Ther., October 1, 2008; 7(10): 3330 - 3342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sato, T. Machida, S. Takahashi, K. Murase, Y. Kawano, T. Hayashi, S. Iyama, K. Takada, K. Kuribayashi, Y. Sato, et al. Apoptosis Supercedes Necrosis in Mitochondrial DNA-Depleted Jurkat Cells by Cleavage of Receptor-Interacting Protein and Inhibition of Lysosomal Cathepsin J. Immunol., July 1, 2008; 181(1): 197 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nishimura, J. Komiyama, Y. Tasaki, T. J. Acosta, and K. Okuda Hypoxia Promotes Luteal Cell Death in Bovine Corpus Luteum Biol Reprod, March 1, 2008; 78(3): 529 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Zhang, J. J. Peairs, P. Yang, J. Tyrrell, J. Roberts, R. Kole, and G. J. Jaffe The Importance of Bcl-xL in the Survival of Human RPE Cells Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3846 - 3853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Kouvaris, V. E. Kouloulias, and L. J. Vlahos Amifostine: The First Selective-Target and Broad-Spectrum Radioprotector Oncologist, June 1, 2007; 12(6): 738 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Degrossoli and S. Giorgio Functional Alterations in Macrophages After Hypoxia Selection Experimental Biology and Medicine, January 1, 2007; 232(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chiarugi "Simple but not simpler": toward a unified picture of energy requirements in cell death FASEB J, November 1, 2005; 19(13): 1783 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yao, S. Shida, M. Selvakumaran, R. Zimmerman, E. Simon, J. Schick, N. B. Haas, M. Balke, H. Ross, S. W. Johnson, et al. Macrophage Migration Inhibitory Factor Is a Determinant of Hypoxia-Induced Apoptosis in Colon Cancer Cell Lines Clin. Cancer Res., October 15, 2005; 11(20): 7264 - 7272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Fink and B. T. Cookson Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells Infect. Immun., April 1, 2005; 73(4): 1907 - 1916. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gozal, L. R. Sachleben Jr., M. J. Rane, C. Vega, and D. Gozal Mild sustained and intermittent hypoxia induce apoptosis in PC-12 cells via different mechanisms Am J Physiol Cell Physiol, March 1, 2005; 288(3): C535 - C542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kida, M. Yoshida, S. Hoshino, K. Inoue, Y. Yano, M. Yanagita, T. Kumagai, T. Osaki, I. Tachibana, Y. Saeki, et al. Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L342 - L349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, X. Zhang, D. P. Sejas, G. C. Bagby, and Q. Pang Hypoxia-induced Nucleophosmin Protects Cell Death through Inhibition of p53 J. Biol. Chem., October 1, 2004; 279(40): 41275 - 41279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Ziegler and P. Groscurth Morphological Features of Cell Death Physiology, June 1, 2004; 19(3): 124 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Yermolaieva, R. Xu, C. Schinstock, N. Brot, H. Weissbach, S. H. Heinemann, and T. Hoshi Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation PNAS, February 3, 2004; 101(5): 1159 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shinzawa and Y. Tsujimoto PLA2 activity is required for nuclear shrinkage in caspase-independent cell death J. Cell Biol., December 22, 2003; 163(6): 1219 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Edwards, D. E. B. Swinson, J. L. Jones, S. Muller, D. A. Waller, and K. J. O'Byrne Tumor Necrosis Correlates With Angiogenesis and Is a Predictor of Poor Prognosis in Malignant Mesothelioma Chest, November 1, 2003; 124(5): 1916 - 1923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Naranjo-Suarez, M. C. Castellanos, M. Alvarez-Tejado, A. Vara, M. O. Landazuri, and L. del Peso Down-regulation of Hypoxia-inducible Factor-2 in PC12 Cells by Nerve Growth Factor Stimulation J. Biol. Chem., August 22, 2003; 278(34): 31895 - 31901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Nicotera Molecular Switches Deciding the Death of Injured Neurons Toxicol. Sci., July 1, 2003; 74(1): 4 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. PAXIAN, I. BAUER, H. RENSING, H. JAESCHKE, A. E. M. MAUTES, S. A. KOLB, B. WOLF, A. STOCKHAUSEN, S. JEBLICK, and M. BAUER Recovery of hepatocellular ATP and "pericentral apoptosis" after hemorrhage and resuscitation FASEB J, June 1, 2003; 17(9): 993 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nakagami, R. Morishita, K. Yamamoto, Y. Taniyama, M. Aoki, K. Yamasaki, K. Matsumoto, T. Nakamura, Y. Kaneda, and T. Ogihara Hepatocyte Growth Factor Prevents Endothelial Cell Death Through Inhibition of bax Translocation From Cytosol to Mitochondrial Membrane Diabetes, August 1, 2002; 51(8): 2604 - 2611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Esco, Z. Wang, M. L. McDermott, and M. Kurpakus-Wheater Potential role for laminin 5 in hypoxia-mediated apoptosis of human corneal epithelial cells J. Cell Sci., March 13, 2002; 114(22): 4033 - 4040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Xiao, L. Wei, S. Xia, S. Rothman, and S. P. Yu Ionic Mechanism of Ouabain-Induced Concurrent Apoptosis and Necrosis in Individual Cultured Cortical Neurons J. Neurosci., February 15, 2002; 22(4): 1350 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shiraishi, T. Tatsumi, N. Keira, K. Akashi, A. Mano, S. Yamanaka, S. Matoba, J. Asayama, T. Yaoi, S. Fushiki, et al. Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1637 - H1647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Sowter, P. J. Ratcliffe, P. Watson, A. H. Greenberg, and A. L. Harris HIF-1-dependent Regulation of Hypoxic Induction of the Cell Death Factors BNIP3 and NIX in Human Tumors Cancer Res., September 1, 2001; 61(18): 6669 - 6673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nakagami, R. Morishita, K. Yamamoto, S.-i. Yoshimura, Y. Taniyama, M. Aoki, H. Matsubara, S. Kim, Y. Kaneda, and T. Ogihara Phosphorylation of p38 Mitogen-Activated Protein Kinase Downstream of Bax-Caspase-3 Pathway Leads to Cell Death Induced by High D-Glucose in Human Endothelial Cells Diabetes, June 1, 2001; 50(6): 1472 - 1481. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Fernandez, T. Udagawa, C. Schwesinger, W.-D. Beecken, E. Achilles-Gerte, T. J. McDonnell, and R. J. D'Amato Angiogenic Potential of Prostate Carcinoma Cells Overexpressing bcl-2 J Natl Cancer Inst, February 7, 2001; 93(3): 208 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Martin, J. R. Bertino, and J. A. Koutcher ATP Depletion + Pyrimidine Depletion Can Markedly Enhance Cancer Therapy: Fresh Insight for a New Approach Cancer Res., December 1, 2000; 60(24): 6776 - 6783. [Full Text]
|
|
|
|
 |
|
 M. I. Koukourakis, G. Kyrias, S. Kakolyris, C. Kouroussis, C. Frangiadaki, A. Giatromanolaki, G. Retalis, and V. Georgoulias Subcutaneous Administration of Amifostine During Fractionated Radiotherapy: A Randomized Phase II Study J. Clin. Oncol., June 11, 2000; 18(11): 2226 - 2233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ogiso, A. Tomida, S. Lei, S. Oura, and T. Tsuruo Proteasome Inhibition Circumvents Solid Tumor Resistance to Topoisomerase II-directed Drugs Cancer Res., May 1, 2000; 60(9): 2429 - 2434. [Abstract] [Full Text]
|
|
|
|
|
|
J. Kim, J Won, S Sohn, and C. Joe DNA-binding activity of the N-terminal cleavage product of poly(ADP-ribose) polymerase is required for UV mediated apoptosis J. Cell Sci., January 3, 2000; 113(6): 955 - 961. [Abstract] [PDF]
|
|
|
|
 |
|
 H Strik, M Deininger, J Streffer, E Grote, J Wickboldt, J Dichgans, M Weller, and R Meyermann BCL-2 Family protein expression in initial and recurrent glioblastomas: modulation by radiochemotherapy J. Neurol. Neurosurg. Psychiatry, December 1, 1999; 67(6): 763 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nomura, S. Shimizu, T. Ito, M. Narita, H. Matsuda, and Y. Tsujimoto Apoptotic Cytosol Facilitates Bax Translocation to Mitochondria That Involves Cytosolic Factor Regulated by Bcl-2 Cancer Res., November 1, 1999; 59(21): 5542 - 5548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-J. Dai, A. Funk, T. Herdegen, T. Unger, J. Culman, and W. M. Armstead Blockade of Central Angiotensin AT1 Receptors Improves Neurological Outcome and Reduces Expression of AP-1 Transcription Factors After Focal Brain Ischemia in Rats • Editorial Comment Stroke, November 1, 1999; 30 (11): 2391 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bilbao, J. L. Contreras, H.-G. Zhang, M. J. Pike, K. Overturf, G. Mikheeva, V. Krasnykh, and D. T. Curiel Adenovirus-Mediated Gene Expression In Vivo Is Enhanced by the Antiapoptotic Bcl-2 Gene J. Virol., August 1, 1999; 73(8): 6992 - 7000. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Eguchi, A. Srinivasan, K. J. Tomaselli, S. Shimizu, and Y. Tsujimoto ATP-dependent Steps in Apoptotic Signal Transduction Cancer Res., May 1, 1999; 59(9): 2174 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Coopersmith, D. O'Donnell, and J. I. Gordon Bcl-2 inhibits ischemia-reperfusion-induced apoptosis in the intestinal epithelium of transgenic mice Am J Physiol Gastrointest Liver Physiol, March 1, 1999; 276(3): G677 - G686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Wassberg, F. Hedborg, E. Skoldenberg, M. Stridsberg, and R. Christofferson Inhibition of Angiogenesis Induces Chromaffin Differentiation and Apoptosis in Neuroblastoma Am. J. Pathol., February 1, 1999; 154(2): 395 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Okuno, S. Shimizu, T. Ito, M. Nomura, E. Hamada, Y. Tsujimoto, and H. Matsuda Bcl-2 Prevents Caspase-independent Cell Death J. Biol. Chem., December 18, 1998; 273(51): 34272 - 34277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Green and John C. Reed Mitochondria and Apoptosis Science, August 28, 1998; 281(5381): 1309 - 1312. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. J. Tuft and P. Luthert Acute Microcystic Corneal Epitheliopathy After Daily Soft Contact Lens Wear Arch Ophthalmol, June 1, 1998; 116(6): 810 - 812. [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Yoshimura, Y. Banno, S. Nakashima, K. Takenaka, H. Sakai, Y. Nishimura, N. Sakai, S. Shimizu, Y. Eguchi, Y. Tsujimoto, et al. Ceramide Formation Leads to Caspase-3 Activation during Hypoxic PC12 Cell Death. INHIBITORY EFFECTS OF Bcl-2 ON CERAMIDE FORMATION AND CASPASE-3 ACTIVATION J. Biol. Chem., March 20, 1998; 273(12): 6921 - 6927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Moallem and B. Hales The role of p53 and cell death by apoptosis and necrosis in 4-hydroperoxycyclophosphamide-induced limb malformations Development, January 8, 1998; 125(16): 3225 - 3234. [Abstract] [PDF]
|
|
|
|
|
|
J. K. Yun, T. S. McCormick, C. Villabona, R. R. Judware, M. B. Espinosa, and E. G. Lapetina Inflammatory mediators are perpetuated in macrophages resistant to apoptosis induced by hypoxia PNAS, December 9, 1997; 94(25): 13903 - 13908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Haddad, Y.-a. Sun, R. J. Wyman, and T. Xu Genetic basis of tolerance to O2 deprivation in Drosophila melanogaster PNAS, September 30, 1997; 94(20): 10809 - 10812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Leist, B. Single, A. F. Castoldi, S. Kuhnle, and P. Nicotera Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis J. Exp. Med., April 21, 1997; 185(8): 1481 - 1486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Suk, I. Chang, Y.-H. Kim, S. Kim, J. Y. Kim, H. Kim, and M.-S. Lee Interferon gamma (IFNgamma ) and Tumor Necrosis Factor alpha Synergism in ME-180 Cervical Cancer Cell Apoptosis and Necrosis. IFNgamma INHIBITS CYTOPROTECTIVE NF-kappa B THROUGH STAT1/IRF-1 PATHWAYS J. Biol. Chem., April 13, 2001; 276(16): 13153 - 13159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Hale, R. D. Braun, W. M. Gwinn, P. K. Greer, and M. W. Dewhirst Hypoxia in the thymus: role of oxygen tension in thymocyte survival Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1467 - H1477. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
