Recent work has shown that Bcl-2 and other anti-apoptotic proteins partially deplete the endoplasmic reticulum (ER) Ca(2+) store and that this alteration of Ca(2+) signaling reduces cellular sensitivity to apoptotic stimuli. We expressed in HeLa cells Bcl-2, Bax, and Bcl-2/Bax chimeras in which the putative pore-forming domains of the two proteins (alpha 5-alpha 6) were mutually swapped, comparing the effects on Ca(2+) signaling of the two proteins and relating them to defined molecular domains. The results showed that only Bcl-2 reduces ER Ca(2+) levels and that this effect does not depend on the alpha 5-alpha 6 helices of this oncoprotein. Soon after its expression, Bax increased ER Ca(2+) loading, with ensuing potentiation of mitochondrial Ca(2+) responses. Then the cells progressed into an apoptotic phenotype (which included drastic reductions of cytosolic and mitochondrial Ca(2+) responses and alterations of organelle morphology). These results provide a coherent scenario that high-lights a primary role of Ca(2+) signals in deciphering apoptotic stimuli.

Chami, M., Prandini, A., Campanella, M., Pinton, P., Szabadkai, G., Reed, J.c., et al. (2004). Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 279(52), 54581-54589 [10.1074/jbc.M409663200].

Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region

Campanella, Michelangelo
;
2004-12-24

Abstract

Recent work has shown that Bcl-2 and other anti-apoptotic proteins partially deplete the endoplasmic reticulum (ER) Ca(2+) store and that this alteration of Ca(2+) signaling reduces cellular sensitivity to apoptotic stimuli. We expressed in HeLa cells Bcl-2, Bax, and Bcl-2/Bax chimeras in which the putative pore-forming domains of the two proteins (alpha 5-alpha 6) were mutually swapped, comparing the effects on Ca(2+) signaling of the two proteins and relating them to defined molecular domains. The results showed that only Bcl-2 reduces ER Ca(2+) levels and that this effect does not depend on the alpha 5-alpha 6 helices of this oncoprotein. Soon after its expression, Bax increased ER Ca(2+) loading, with ensuing potentiation of mitochondrial Ca(2+) responses. Then the cells progressed into an apoptotic phenotype (which included drastic reductions of cytosolic and mitochondrial Ca(2+) responses and alterations of organelle morphology). These results provide a coherent scenario that high-lights a primary role of Ca(2+) signals in deciphering apoptotic stimuli.
24-dic-2004
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Adenosine Triphosphate
Aequorin
Apoptosis
Calcium
Cloning, Molecular
Endoplasmic Reticulum
Fluorescent Antibody Technique
HeLa Cells
Homeostasis
Humans
Mitochondria
Protein Structure, Secondary
Proto-Oncogene Proteins c-bcl-2
Recombinant Fusion Proteins
Structure-Activity Relationship
Transfection
bcl-2-Associated X Protein
Signal Transduction
Gene Expression
Chami, M., Prandini, A., Campanella, M., Pinton, P., Szabadkai, G., Reed, J.c., et al. (2004). Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 279(52), 54581-54589 [10.1074/jbc.M409663200].
Chami, M; Prandini, A; Campanella, M; Pinton, P; Szabadkai, G; Reed, Jc; Rizzuto, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/265755
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