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

Bcl-2 is a gene with clear anti-apoptotic properties in neurodegenerative c onditions. One of the earliest hallmarks of degeneration in neuronal cell c ultures 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 ag ainst both taxol- and okadaic acid induced neurite retraction. Bcl-2 overex pression also significantly reduced the increased ratio of acetylated tubul in over total tubulin induced by taxol treatment. Interestingly, Bcl-2 atte nuates the decrease of the same ratio after exposure to okadaic acid, sugge sting that Bcl-2 is able to normalize the level of acetylated tubulin. In a ddition, cell death and nuclear fragmentation, induced by okadaic acid, wer e reduced in Bcl-2 overexpressing cells. This protection is either downstre am or independent of tau phosphorylation as quantitative immunocytochemistr y with AT8 showed that Bcl-2 did not modify the level of tau phosphorylatio n. The data suggest that the protective effect of Bcl-2 on the neuronal cyt oskeleton is probably linked to changes in the post-translational modificat ion of tubulin.