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| Reduced loading of intracellular Ca2+ stores and downregulation of capacitative Ca2+ influx in Bcl-2-overexpressing cells |
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| Author(s): Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di Virgilio F, Pozzan T, Rizzuto R |
| Source: JOURNAL OF CELL BIOLOGY Volume: 148 Issue: 5 Pages: 857-862 Published: MAR 6 2000 |
| Times Cited: 212 References: 33 |
| Abstract: 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+ in flux 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Rizzuto, R (reprint author), Dept Expt & Diagnost Med, Sect Gen Pathol, Via Borsari 46, I-44100 Ferrara, Italy |
Addresses:
1. Dept Expt & Diagnost Med, Sect Gen Pathol, I-44100 Ferrara, Italy
2. Univ Padua, CNR, Ctr Study Biomembranes, I-35121 Padua, Italy
3. Univ Tubingen, D-72076 Tubingen, Germany |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA |
| Subject Category: Cell Biology |
| IDS Number: 292CC |
| ISSN: 0021-9525 |
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