Bcl-x(L) inhibits Bax-induced alterations in mitochondrial respiration and calcium release.
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.
Teles
A V F
AV
Departamento de Farmacologia, Universidade Federal de São Paulo (Department of Pharmacology, Federal University of São Paulo), Rua Tres de Maio-100, São Paulo 04044-020, Brazil.
Ureshino
R P
RP
Dorta
D J
DJ
Lopes
G S
GS
Hsu
Y-T
YT
Smaili
S S
SS
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure*; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000494:pharmacology*; D051020:bcl-X Protein / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007476:Ionophores; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D015759:Ionomycin; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2