title: Endoplasmic reticulum calcium release engages Bax translocation in cortical astrocytes.
abstract: Apoptosis is a highly complex form of cell death that can be triggered by alterations in Ca(2+) homeostasis. Members of the Bcl-2 family may regulate apoptosis and modulate Ca(2+) distribution within intracellular compartments. Bax, a proapoptotic member of the family, is constitutively expressed and soluble in the cytosol and, under apoptotic induction, translocates to mitochondrial membranes. However, it is not clear if the intracellular Ca(2+) stores and selective Ca(2+) releases can modulate or control Bax translocation. The aim of this study was to investigate the relation of intracellular Ca(2+) stores with Bax translocation in rat cortical astrocytes. Results show that the classical apoptotic inducer, staurosporine, caused high elevations of cytosolic Ca(2+) that precede Bax translocation. On the other hand, agents that mobilize Ca(2+) from endoplasmic reticulum such as noradrenaline or thapsigargin, induced Bax translocation, while mitochondrial Ca(2+) release evoked by carbonyl cyanide-p-(trifluoromethoxyphenyl) hydrazone was not able to cause Bax punctation. In addition, microinjection of inositol 1,4,5- trisphosphate induced Bax translocation. Taken together, our results show that in Bax overexpressing cortical astrocytes, endoplasmic reticulum-Ca(2+) release may induce Bax transactivation and specifically control apoptosis.
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), Rua Três de Maio 100, CEP 04044-020 São Paulo, SP, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Morales
authors.forename: A C P
authors.initials: AC
authors.lastname: Carvalho
authors.forename: P T
authors.initials: PT
authors.lastname: Monteforte
authors.forename: H
authors.initials: H
authors.lastname: Hirata
authors.forename: S W
authors.initials: SW
authors.lastname: Han
authors.forename: Y-T
authors.initials: YT
authors.lastname: Hsu
authors.forename: S S
authors.initials: SS
authors.lastname: Smaili
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005434:Flow Cytometry; D008845:Microinjections; D021381:Protein Transport; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051028:bcl-2-Associated X Protein; D002118:Calcium