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J. Cell Biol. 150 (4): 887-894

Copyright © 2000 by the Rockefeller University Press.

Report

Cross-Talk between Two Cysteine Protease Families

Activation of Caspase-12 by Calpain in Apoptosis

Toshiyuki Nakagawaa, and Junying Yuana

a Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115.(617) 432-4177(617) 432-4170

jyuan{at}hms.harvard.edu

Abstract: Calpains and caspases are two cysteine protease families that play important roles in regulating pathological cell death. Here, we report that m-calpain may be responsible for cleaving procaspase-12, a caspase localized in the ER, to generate active caspase-12. In addition, calpain may be responsible for cleaving the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into a proapoptotic molecule. We propose that disturbance to intracellular calcium storage as a result of ischemic injury or amyloid β peptide cytotoxicity may induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL inactivation. These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families.

Key Words: calcium • Alzheimer's disease • Bcl-xL • endoplasmic reticulum • ER stress

Abbreviations used in this paper: Aβ, amyloid β; IP3R, inositol 1,4,5-trisphosphate receptor; OD, oxygen deprivation; OGD, oxygen and glucose deprivation; t-caspase-12, T159-N419 caspase-12.

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AMP-Activated Protein Kinase Protects Cardiomyocytes against Hypoxic Injury through Attenuation of Endoplasmic Reticulum Stress.
K. Terai, Y. Hiramoto, M. Masaki, S. Sugiyama, T. Kuroda, M. Hori, I. Kawase, and H. Hirota (2005)
Mol. Cell. Biol. 25, 9554-9575
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress Signal Mediators Are Targets of Selenium Action.
Y. Wu, H. Zhang, Y. Dong, Y.-M. Park, and C. Ip (2005)
Cancer Res. 65, 9073-9079
   Abstract »    Full Text »    PDF »
Involvement of Intracellular Ca2+ Levels in Nonsteroidal Anti-inflammatory Drug-induced Apoptosis.
K.-i. Tanaka, W. Tomisato, T. Hoshino, T. Ishihara, T. Namba, M. Aburaya, T. Katsu, K. Suzuki, S. Tsutsumi, and T. Mizushima (2005)
J. Biol. Chem. 280, 31059-31067
   Abstract »    Full Text »    PDF »
Caspase-12 and Caspase-4 Are Not Required for Caspase-dependent Endoplasmic Reticulum Stress-induced Apoptosis.
E. A. Obeng and L. H. Boise (2005)
J. Biol. Chem. 280, 29578-29587
   Abstract »    Full Text »    PDF »
Regulation of N-Methyl-D-aspartate Receptors by Calpain in Cortical Neurons.
H.-Y. Wu, E. Y. Yuen, Y.-F. Lu, M. Matsushita, H. Matsui, Z. Yan, and K. Tomizawa (2005)
J. Biol. Chem. 280, 21588-21593
   Abstract »    Full Text »    PDF »
Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors.
R. S. Maag, M. Mancini, A. Rosen, and C. E. Machamer (2005)
Mol. Biol. Cell 16, 3019-3027
   Abstract »    Full Text »    PDF »
Mitochondrial-Mediated Disregulation of Ca2+ Is a Critical Determinant of Velcade (PS-341/Bortezomib) Cytotoxicity in Myeloma Cell Lines.
T. H. Landowski, C. J. Megli, K. D. Nullmeyer, R. M. Lynch, and R. T. Dorr (2005)
Cancer Res. 65, 3828-3836
   Abstract »    Full Text »    PDF »
Distinct Mechanistic Roles of Calpain and Caspase Activation in Neurodegeneration as Revealed in Mice Overexpressing Their Specific Inhibitors.
M. Higuchi, M. Tomioka, J. Takano, K. Shirotani, N. Iwata, H. Masumoto, M. Maki, S. Itohara, and T. C. Saido (2005)
J. Biol. Chem. 280, 15229-15237
   Abstract »    Full Text »    PDF »
Molecular cloning and characterization of murine caspase-12 gene promoter.
H. Oubrahim, J. Wang, E. R. Stadtman, and P. B. Chock (2005)
PNAS 102, 2322-2327
   Abstract »    Full Text »    PDF »
Cleavage of Nonmuscle Myosin Heavy Chain-A during Apoptosis in Human Jurkat T Cells.
M. Kato, H. Fukuda, T. Nonaka, and S. Imajoh-Ohmi (2005)
J. Biochem. 137, 157-166
   Abstract »    Full Text »    PDF »
Camptothecin- and etoposide-induced apoptosis in human leukemia cells is independent of cell death receptor-3 and -4 aggregation but accelerates tumor necrosis factor-related apoptosis-inducing ligand-mediated cell death.
S. Bergeron, M. Beauchemin, and R. Bertrand (2004)
Mol. Cancer Ther. 3, 1659-1669
   Abstract »    Full Text »    PDF »
Translocation of Bim to the Endoplasmic Reticulum (ER) Mediates ER Stress Signaling for Activation of Caspase-12 during ER Stress-induced Apoptosis.
N. Morishima, K. Nakanishi, K. Tsuchiya, T. Shibata, and E. Seiwa (2004)
J. Biol. Chem. 279, 50375-50381
   Abstract »    Full Text »    PDF »
The Mitochondrial Death Pathway and Cardiac Myocyte Apoptosis.
M. T. Crow, K. Mani, Y.-J. Nam, and R. N. Kitsis (2004)
Circ. Res. 95, 957-970
   Abstract »    Full Text »    PDF »
Calcium-Dependent Calpain Proteases Are Implicated in Processing of the Hepatitis C Virus NS5A Protein.
M. Kalamvoki and P. Mavromara (2004)
J. Virol. 78, 11865-11878
   Abstract »    Full Text »    PDF »
Edaravone Protects against Hypoxia/Ischemia-Induced Endoplasmic Reticulum Dysfunction.
X. Qi, Y. Okuma, T. Hosoi, and Y. Nomura (2004)
J. Pharmacol. Exp. Ther. 311, 388-393
   Abstract »    Full Text »    PDF »
Oxidative Stress-induced Apoptosis in Retinal Photoreceptor Cells Is Mediated by Calpains and Caspases and Blocked by the Oxygen Radical Scavenger CR-6.
N. Sanvicens, V. Gomez-Vicente, I. Masip, A. Messeguer, and T. G. Cotter (2004)
J. Biol. Chem. 279, 39268-39278
   Abstract »    Full Text »    PDF »
Proapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals.
E. A. Jonas, J. A. Hickman, M. Chachar, B. M. Polster, T. A. Brandt, Y. Fannjiang, I. Ivanovska, G. Basanez, K. W. Kinnally, J. Zimmerberg, et al. (2004)
PNAS 101, 13590-13595
   Abstract »    Full Text »    PDF »
Cleavage of Calnexin Caused by Apoptotic Stimuli: Implication for the Regulation of Apoptosis.
T. Takizawa, C. Tatematsu, K. Watanabe, K. Kato, and Y. Nakanishi (2004)
J. Biochem. 136, 399-405
   Abstract »    Full Text »    PDF »

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