Bcl-XL inhibits Bax-induced alterations in mitochondrial respiration and calcium release

被引：20

作者：

Teles, A. V. F. ^{[1
]}

Ureshino, R. P. ^{[1
]}

Dorta, D. J. ^{[1
]}

Lopes, G. S. ^{[1
]}

Hsu, Y. -T. ^{[2
]}

Smaili, S. S. ^{[1
]}

机构：

[1] Univ Fed Sao Paulo, Dept Farmacol, BR-04044020 Sao Paulo, Brazil

[2] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA

来源：

NEUROSCIENCE LETTERS | 2008年 / 442卷 / 02期

基金：

巴西圣保罗研究基金会;

关键词：

Bcl-X-L; Bax; calcium; apoptosis; mitochondria; respiratory chain; ATP; ADP; cell death;

D O I：

10.1016/j.neulet.2008.06.073

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Apoptosis is a natural cell elimination process involved in a number of physiological and pathological events. This process can be regulated by members of the Bcl-2 family. Bax, a pro-apoptotic member of this family, accelerates cell death, while the pro-survival member, Bcl-X-L, can antagonize the pro-apoptotic function of Bax to promote cell survival. In the present study, we have evaluated the effect of Bcl-X-L on Bax-induced alterations in mitochondrial. respiration and calcium release. We found that in primary cultured astrocytes, recombinant Bcl-X-L is able to antagonize Bax-induced decrease in mitochondrial respiration and increase in mitochondrial. calcium release. In addition, we found that Bcl-X-L can lower the calcium store in the endoplasmic reticulum, thus limiting potential calcium flux induced by apoptosis. This regulation of calcium flux by Bcl-X-L may represent an important mechanism by which this protein promotes cell survival. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：96 / 99

页数：4

共 29 条

[1]

Bax-type apoptotic proteins porate pure lipid bilayers through a mechanism sensitive to intrinsic monolayer curvature [J].

Basañez, G ;

Sharpe, JC ;

Galanis, J ;

Brandt, TB ;

Hardwick, JM ;

Zimmerberg, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (51) :49360-49365

[2]

Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis [J].

Boehning, D ;

Patterson, RL ;

Sedaghat, L ;

Glebova, NO ;

Kurosaki, T ;

Snyder, SH .

NATURE CELL BIOLOGY, 2003, 5 (12) :1051-1061

[3]

Bax affects intracellular Ca2+ stores and induces Ca2+ wave propagation [J].

Carvalho, ACP ;

Sharpe, J ;

Rosenstock, TR ;

Teles, AFV ;

Youle, RJ ;

Smaili, SS .

CELL DEATH AND DIFFERENTIATION, 2004, 11 (12) :1265-1276

[4]

BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis [J].

Cheng, EHYA ;

Wei, MC ;

Weiler, S ;

Flavell, RA ;

Mak, TW ;

Lindsten, T ;

Korsmeyer, SJ .

MOLECULAR CELL, 2001, 8 (03) :705-711

[5]

Apoptosis - the calcium connection [J].

Demaurex, N ;

Distelhorst, C .

SCIENCE, 2003, 300 (5616) :65-67

[6]

Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL [J].

Finucane, DM ;

Bossy-Wetzel, E ;

Waterhouse, NJ ;

Cotter, TG ;

Green, DR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (04) :2225-2233

[7]

Bcl-XL and calyculin A prevent translocation of Bax to mitochondria during apoptosis [J].

Ganju, N ;

Eastman, A .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 291 (05) :1258-1264

[8]

The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant [J].

Goldstein, JC ;

Waterhouse, NJ ;

Juin, P ;

Evan, GI ;

Green, DR .

NATURE CELL BIOLOGY, 2000, 2 (03) :156-162

[9]

GONZALEZGARCIA M, 1994, DEVELOPMENT, V120, P3033

[10]

Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis [J].

Gross, A ;

Jockel, J ;

Wei, MC ;

Korsmeyer, SJ .

EMBO JOURNAL, 1998, 17 (14) :3878-3885

← 1 2 3 →