Bcl-2 protects against apoptosis-related microtubule alterations in neuronal cells

• Published in: Apoptosis (London) 2000-02, Vol.5 (1), p.43-51
• Main Authors: Nuydens, R, Dispersyn, G, Van Den Keiboom, G, de Jong, M, Connors, R, Ramaekers, F, Borgers, M, Geerts, H
• Format: Article
• Language: English
• Subjects: Acetylation - drug effects; Animals; Apoptosis; Cell Survival; Enzyme-Linked Immunosorbent Assay; Genes, bcl-2; Microtubules - metabolism; Neurites - drug effects; Neurites - ultrastructure; Neurons - drug effects; Neurons - ultrastructure; Okadaic Acid - pharmacology; Paclitaxel - pharmacology; Phosphorylation; Phosphorylation - drug effects; Protein Processing, Post-Translational; Proteins; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Rats; tau Proteins - metabolism; Transfection
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1023/A:1009685609275

Bcl-2 is a gene with clear anti-apoptotic properties in neurodegenerative conditions. One of the earliest hallmarks of degeneration in neuronal cell cultures is the loss of neurite morphology. Therefore the effect of Bcl-2 on neuronal morphology and microtubule stability was studied in nerve growth factor differentiated PC12 cells. Microtubule dynamics were modulated using the microtubule stabilizer taxol and the microtubule destabilizer, okadaic acid, a protein phosphatase inhibitor. It was shown that Bcl-2 protects against both taxol- and okadaic acid induced neurite retraction. Bcl-2 overexpression also significantly reduced the increased ratio of acetylated tubulin over total tubulin induced by taxol treatment. Interestingly, Bcl-2 attenuates the decrease of the same ratio after exposure to okadaic acid, suggesting that Bcl-2 is able to normalize the level of acetylated tubulin. In addition, cell death and nuclear fragmentation, induced by okadaic acid, were reduced in Bcl-2 overexpressing cells. This protection is either downstream or independent of tau phosphorylation as quantitative immunocytochemistry with AT8 showed that Bcl-2 did not modify the level of tau phosphorylation. The data suggest that the protective effect of Bcl-2 on the neuronal cytoskeleton is probably linked to changes in the post-translational modification of tubulin.