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© The Rockefeller University Press, 0021-9525/2000//857 $5.00
The Journal of Cell Biology, Volume 148, Number 5, , 2000 857-862

Brief Report

Reduced Loading of Intracellular Ca2+ Stores and Downregulation of Capacitative Ca2+Influx in Bcl-2–Overexpressing Cells



Paolo Pintonb, Davide Ferraria, Paulo Magalhãesb, Klaus Schulze-Osthoffc, Francesco Di Virgilioa, Tullio Pozzanb, and Rosario Rizzutoa

a Department of Experimental and Diagnostic Medicine, Section of General Pathology, 44100 Ferrara, Italy
b Department of Biomedical Sciences and Consiglio Nazionale delle Ricerche (CNR) Center for the Study of Biomembranes, University of Padova, 35121 Padova, Italy
c Eberhard-Karls University, 72076 Tübingen, Germany
Department of Experimental and Diagnostic Medicine, Section of General Pathology, Via Borsari 46, 44100 Ferrara, Italy.39 49 828 657639 49 828 6569

r.rizzuto{at}unife.it

The mechanism of action of the oncogene bcl-2, a key regulator of the apoptotic process, is still debated. We have employed organelle-targeted chimeras of the Ca2+-sensitive photoprotein, aequorin, to investigate in detail the effect of Bcl-2 overexpression on intracellular Ca2+ homeostasis. In the ER and the Golgi apparatus, Bcl-2 overexpression increases the Ca2+ leak (while leaving Ca2+ accumulation unaffected), hence reducing the steady-state [Ca2+] levels. As a direct consequence, the [Ca2+] increases caused by inositol 1,4,5 trisphosphate (IP3)-generating agonists were reduced in amplitude in both the cytosol and the mitochondria. Bcl-2 overexpression also reduced the rate of Ca2+ influx activated by Ca2+ store depletion, possibly by an adaptive downregulation of this pathway. By interfering with Ca2+-dependent events at multiple intracellular sites, these effects of Bcl-2 on intracellular Ca2+ homeostasis may contribute to the protective role of this oncogene against programed cell death.

Key Words: calcium • organelles • oncogene • aequorin • cell signaling

© 2000 The Rockefeller University Press

Abbreviations used in this paper: AEQ, aequorin; cytAEQ, cytosolic AEQ; erAEQ, AEQ chimera targeted to the ER; GFP, green fluorescent protein; GoAEQ, AEQ chimera targeted to the Golgi apparatus; IB, intracellular buffer; IP3, inositol 1,4,5 trisphosphate; KRB, Krebs-Ringer modified buffer; mtAEQ, mitochondrial AEQ; mtGFP, mitochondrially targeted GFP; SERCA, sarcoendoplasmic reticulum Ca2+ ATPases; tBuBHQ, 2,5-di-(tert-butyl)-1,4-benzohydroquinone.


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