Adenovirus-mediated transfer of Bcl-X(L) protects neuronal cells from Bax-induced apoptosis.

Abstract:

: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-X(L), protect cells from Bax-induced apoptosis and show distinct expression patterns in adult neurons, with downregulated Bcl-2 and highly upregulated Bcl-X(L) expression. To investigate the biological functions of these two molecules in Bax-mediated apoptosis in neurons, we transduced various levels of Bcl-X(L) or 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-X(L) expressed 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-X(L) protected PC12 cells from apoptosis induced by NGF withdrawal. These data indicate that Bcl-X(L)-mediated protection is the major pathway that suppresses apoptosis in NGF-treated PC12 cells and that Bcl-X(L) would be a more relevant target of manipulation in future treatment strategies, including gene therapies.

journal_name

Exp Cell Res

authors

Shinoura N,Satou R,Yoshida Y,Asai A,Kirino T,Hamada H

doi

10.1006/excr.1999.4751

keywords:

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

221-31

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(99)94751-1

journal_volume

254

pub_type

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