Bcl-2 protects against apoptosis-related microtubule alterations in neuronal cells.
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.
Department of Cell Physiology, Janssen Research Foundation, Beerse, Belgium.
R
R
Nuydens
G
G
Dispersyn
G
G
Van Den Keiboom
M
M
de Jong
R
R
Connors
F
F
Ramaekers
M
M
Borgers
H
H
Geerts
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D019254:Genes, bcl-2; D008870:Microtubules / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D019319:Okadaic Acid / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D016875:tau Proteins; D019319:Okadaic Acid; D017239:Paclitaxel