 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, July 1, 2001, 21(13):4657-4667
Taxol Induces Apoptosis in Cortical Neurons by a Mechanism Independent of Bcl-2 Phosphorylation
Xavier A. Figueroa-Masot, Michal Hetman, Matthew J. Higgins, Niels Kokot, and Zhengui Xia Departments of Environmental Health and Pharmacology, Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, Washington 98195-7234
Bcl-2, an antiapoptotic protein, protects cells against many but not all forms of apoptosis. For example, Bcl-2 does not protect non-neuronal cells against taxol, a microtubule-stabilizing agent. The underlying mechanism for the ineffectiveness of Bcl-2 against taxol has been the subject of intense interest. Data from non-neuronal cells indicate that taxol-induced apoptosis requires activation of N-terminal c-Jun protein kinase (JNK) that phosphorylates and inactivates Bcl-2. This suggests the interesting possibility that the apoptotic activity of JNK may be caused by phosphorylation of Bcl-2 and inhibition of the antiapoptotic activity of Bcl-2. Here we report that taxol induces apoptosis in cortical neurons but by a mechanism significantly different from that in non-neuronal cells. In contrast to human embryonic kidney 293 cells, expression of wild-type Bcl-2 in cortical neurons protected against taxol-induced apoptosis, and taxol did not induce Bcl-2 phosphorylation. Furthermore, cortical neurons express high basal JNK activity, and taxol did not stimulate total JNK activity. However, taxol activated a subpool of JNK in the nucleus and stimulated c-Jun phosphorylation. JNK inhibition or expression of a dominant-negative c-Jun abrogated taxol-induced apoptosis in cortical neurons, suggesting a role for JNK and JNK-mediated transcription in taxol-stimulated apoptosis. Furthermore, taxol-induced apoptosis in cortical neurons required inhibition of phosphatidylinositol 3-kinase signaling. These data suggest that taxol induces apoptosis in neurons by a mechanism quite distinct from that of non-neuronal cell lines and emphasize the importance of elucidating apoptotic mechanisms specific for neurons in the CNS.
Key words: cortical neurons; N-terminal c-Jun kinase; SAPK; JNK; CEP-1347; KT7515; taxol; paclitaxel; Bcl-2; PI 3-kinase; Akt; ERK1/2; apoptosis
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134657-11$05.00/0
This article has been cited by other articles:
L. J. Martin, Z. Liu, J. Pipino, B. Chestnut, and M. A. Landek
Molecular Regulation of DNA Damage-Induced Apoptosis in Neurons of Cerebral Cortex
Cereb Cortex, September 26, 2008; (2008) bhn167v1.
[Abstract] [Full Text] [PDF]
T. Kabuta, R. Setsuie, T. Mitsui, A. Kinugawa, M. Sakurai, S. Aoki, K. Uchida, and K. Wada
Aberrant molecular properties shared by familial Parkinson's disease-associated mutant UCH-L1 and carbonyl-modified UCH-L1
Hum. Mol. Genet., May 15, 2008; 17(10): 1482 - 1496.
[Abstract] [Full Text] [PDF]
H. Klintworth, K. Newhouse, T. Li, W.-S. Choi, R. Faigle, and Z. Xia
Activation of c-Jun N-Terminal Protein Kinase Is a Common Mechanism Underlying Paraquat- and Rotenone-Induced Dopaminergic Cell Apoptosis
Toxicol. Sci., May 1, 2007; 97(1): 149 - 162.
[Abstract] [Full Text] [PDF]
B. Cai, S. H. Chang, E. B. E. Becker, A. Bonni, and Z. Xia
p38 MAP Kinase Mediates Apoptosis through Phosphorylation of BimEL at Ser-65
J. Biol. Chem., September 1, 2006; 281(35): 25215 - 25222.
[Abstract] [Full Text] [PDF]
B.-J. Kim, S.-W. Ryu, and B.-J. Song
JNK- and p38 Kinase-mediated Phosphorylation of Bax Leads to Its Activation and Mitochondrial Translocation and to Apoptosis of Human Hepatoma HepG2 Cells
J. Biol. Chem., July 28, 2006; 281(30): 21256 - 21265.
[Abstract] [Full Text] [PDF]
J. Jaworski, S. Spangler, D. P. Seeburg, C. C. Hoogenraad, and M. Sheng
Control of Dendritic Arborization by the Phosphoinositide-3'-Kinase-Akt-Mammalian Target of Rapamycin Pathway
J. Neurosci., December 7, 2005; 25(49): 11300 - 11312.
[Abstract] [Full Text] [PDF]
I. M. Muller, V. M. Dirsch, A. Rudy, N. Lopez-Anton, G. R. Pettit, and A. M. Vollmar
Cephalostatin 1 Inactivates Bcl-2 by Hyperphosphorylation Independent of M-Phase Arrest and DNA Damage
Mol. Pharmacol., May 1, 2005; 67(5): 1684 - 1689.
[Abstract] [Full Text] [PDF]
H. Hu, C. Jiang, C. Ip, Y. M. Rustum, and J. Lu
Methylseleninic Acid Potentiates Apoptosis Induced by Chemotherapeutic Drugs in Androgen-Independent Prostate Cancer Cells
Clin. Cancer Res., March 15, 2005; 11(6): 2379 - 2388.
[Abstract] [Full Text] [PDF]
M. L. Michaelis, S. Ansar, Y. Chen, E. R. Reiff, K. I. Seyb, R. H. Himes, K. L. Audus, and G. I. Georg
{beta}-Amyloid-Induced Neurodegeneration and Protection by Structurally Diverse Microtubule-Stabilizing Agents
J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 659 - 668.
[Abstract] [Full Text] [PDF]
K. Newhouse, S.-L. Hsuan, S. H. Chang, B. Cai, Y. Wang, and Z. Xia
Rotenone-Induced Apoptosis Is Mediated By p38 And JNK MAP Kinases In Human Dopaminergic SH-SY5Y Cells
Toxicol. Sci., May 1, 2004; 79(1): 137 - 146.
[Abstract] [Full Text] [PDF]
S. H. Chang, S. Poser, and Z. Xia
A Novel Role For Serum Response Factor in Neuronal Survival
J. Neurosci., March 3, 2004; 24(9): 2277 - 2285.
[Abstract] [Full Text] [PDF]
A. Caughlan, K. Newhouse, U. Namgung, and Z. Xia
Chlorpyrifos Induces Apoptosis in Rat Cortical Neurons that is Regulated by a Balance Between p38 and ERK/JNK MAP Kinases
Toxicol. Sci., March 1, 2004; 78(1): 125 - 134.
[Abstract] [Full Text] [PDF]
L. Liu, J. E. Cavanaugh, Y. Wang, H. Sakagami, Z. Mao, and Z. Xia
ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons
PNAS, July 8, 2003; 100(14): 8532 - 8537.
[Abstract] [Full Text] [PDF]
J. A. Chuckowree and J. C. Vickers
Cytoskeletal and Morphological Alterations Underlying Axonal Sprouting after Localized Transection of Cortical Neuron Axons In Vitro
J. Neurosci., May 1, 2003; 23(9): 3715 - 3725.
[Abstract] [Full Text] [PDF]
R. E. Brown and J. L. Boyle
Mesenchymal Chondrosarcoma: Molecular Characterization by a Proteomic Approach, with Morphogenic and Therapeutic Implications
Ann. Clin. Lab. Sci., April 1, 2003; 33(2): 131 - 141.
[Abstract] [Full Text] [PDF]
V. Waetzig and T. Herdegen
A Single c-Jun N-terminal Kinase Isoform (JNK3-p54) Is an Effector in Both Neuronal Differentiation and Cell Death
J. Biol. Chem., January 3, 2003; 278(1): 567 - 572.
[Abstract] [Full Text] [PDF]
M. Hetman, S.-L. Hsuan, A. Habas, M. J. Higgins, and Z. Xia
ERK1/2 Antagonizes Glycogen Synthase Kinase-3beta -induced Apoptosis in Cortical Neurons
J. Biol. Chem., December 13, 2002; 277(51): 49577 - 49584.
[Abstract] [Full Text] [PDF]
J. Zhou, K. Gupta, J. Yao, K. Ye, D. Panda, P. Giannakakou, and H. C. Joshi
Paclitaxel-resistant Human Ovarian Cancer Cells Undergo c-Jun NH2-terminal Kinase-mediated Apoptosis in Response to Noscapine
J. Biol. Chem., October 11, 2002; 277(42): 39777 - 39785.
[Abstract] [Full Text] [PDF]
M. H. Ghahremani, E. Keramaris, T. Shree, Z. Xia, R. J. Davis, R. Flavell, R. S. Slack, and D. S. Park
Interaction of the c-Jun/JNK Pathway and Cyclin-dependent Kinases in Death of Embryonic Cortical Neurons Evoked by DNA Damage
J. Biol. Chem., September 13, 2002; 277(38): 35586 - 35596.
[Abstract] [Full Text] [PDF]
M. Rapoport, H. N. Dawson, L. I. Binder, M. P. Vitek, and A. Ferreira
Tau is essential to beta -amyloid-induced neurotoxicity
PNAS, April 30, 2002; 99(9): 6364 - 6369.
[Abstract] [Full Text] [PDF]
M. Kruidering, T. Schouten, G. I. Evan, and E. Vreugdenhil
Caspase-mediated Cleavage of the Ca2+/Calmodulin-dependent Protein Kinase-like Kinase Facilitates Neuronal Apoptosis
J. Biol. Chem., October 12, 2001; 276(42): 38417 - 38425.
[Abstract] [Full Text] [PDF]
M. Rapoport, H. N. Dawson, L. I. Binder, M. P. Vitek, and A. Ferreira
Tau is essential to beta -amyloid-induced neurotoxicity
PNAS, April 30, 2002; 99(9): 6364 - 6369.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|