Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Taxol induces apoptosis in cortical neurons by a mechanism independent of Bcl-2 phosphorylation.

Authors: Figueroa-Masot, X A; Hetman, M; Higgins, M J; Kokot, N; Xia, Z

Published In J Neurosci, (2001 Jul 01)

Abstract: 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.

PubMed ID: 11425893 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis*; Cell Nucleus/drug effects; Cell Nucleus/metabolism; Cell Survival/drug effects; Cells, Cultured; Cerebral Cortex/cytology; Cerebral Cortex/drug effects*; Cerebral Cortex/metabolism; Enzyme Activation/drug effects; Enzyme Inhibitors/pharmacology; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; Kidney/cytology; Kidney/drug effects; Kidney/metabolism; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors; Mitogen-Activated Protein Kinases/metabolism; Neurons/cytology; Neurons/drug effects*; Neurons/metabolism; Paclitaxel/pharmacology*; Phosphatidylinositol 3-Kinases/antagonists & inhibitors; Phosphatidylinositol 3-Kinases/metabolism; Phosphorylation/drug effects; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism*; Proto-Oncogene Proteins/metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction/drug effects; Transcription, Genetic; Transfection

Back
to Top