Adenovirus-Mediated Transfer of Bcl-XLProtects Neuronal Cells from Bax-Induced Apoptosis

Bax-mediated apoptosis in neurons is involved in many pathologic conditions affecting the central nervous system, including degenerative diseases, stroke, and trauma. Two molecules belonging to the Bcl-2 family, Bcl-2 and Bcl-XL, protect cells from Bax-induced apoptosis and show distinct expression patterns in adult neurons, with downregulated Bcl-2 and highly upregulated Bcl-XLexpression. To investigate the biological functions of these two molecules in Bax-mediated apoptosis in neurons, we transduced various levels of Bcl-XLor Bcl-2 via adenoviral vectors into nerve growth factor (NGF)-treated PC12 cells. Overexpression of Bax induced drastic apoptosis in NGF-treated PC12 cells. Bcl-XLexpressed at a wide range of levels conferred a high level of protection against Bax-mediated apoptosis. In contrast, Bcl-2 at various levels conferred far less protection against apoptosis. Moreover, Bcl-XLprotected PC12 cells from apoptosis induced by NGF withdrawal. These data indicate that Bcl-XL-mediated protection is the major pathway that suppresses apoptosis in NGF-treated PC12 cells and that Bcl-XLwould be a more relevant target of manipulation in future treatment strategies, including gene therapies.