Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum
| Autor: | Karl-Heinz Krause, Reyhaneh Foyouzi-Youssefi, Serge Arnaudeau, Christoph Borner, Daniel Pablo Lew, Nicolas Demaurex, William L. Kelley, Jürg Tschopp |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Intracellular Fluid
Calcium/ metabolism Thapsigargin Fura-2 Recombinant Fusion Proteins Apoptosis Calcium Signaling/physiology Biology Mitochondrion Endoplasmic Reticulum Transfection Permeability Cell Line chemistry.chemical_compound Mice Tumor Cells Cultured Animals Humans Calcium Signaling Intracellular Fluid/metabolism Ion channel Calcium signaling ddc:616 Multidisciplinary Recombinant Fusion Proteins/physiology Endoplasmic reticulum Proto-Oncogene Proteins c-bcl-2/ physiology Fura-2/analogs & derivatives/metabolism Apoptosis/physiology Cameleon (protein) Biological Sciences Endoplasmic Reticulum/ metabolism Cell biology Genes bcl-2 chemistry Proto-Oncogene Proteins c-bcl-2 biology.protein Calcium Intracellular |
| Zdroj: | Proceedings of the National Academy of Sciences, Vol. 97, No 11 (2000) pp. 5723-5728 |
| ISSN: | 0027-8424 |
| Popis: | The antiapoptotic protein Bcl-2 localizes not only to mitochondria but also to the endoplasmic reticulum (ER). However, the function of Bcl-2 at the level of the ER is poorly understood. In this study, we have investigated the effects of Bcl-2 expression on Ca 2+ storage and release by the ER. The expression of Bcl-2 decreased the amount of Ca 2+ that could be released from intracellular stores, regardless of the mode of store depletion, the cell type, or the species from which Bcl-2 was derived. Bcl-2 also decreased cellular Ca 2+ store content in the presence of mitochondrial inhibitors, suggesting that its effects were not mediated through mitochondrial Ca 2+ uptake. Direct measurements with ER-targeted Ca 2+ -sensitive fluorescent “cameleon” proteins revealed that Bcl-2 decreased the free Ca 2+ concentration within the lumen of the ER, [Ca 2+ ] ER . Analysis of the kinetics of Ca 2+ store depletion in response to the Ca 2+ -ATPase inhibitor thapsigargin revealed that Bcl-2 increased the permeability of the ER membrane. These results suggest that Bcl-2 decreases the free Ca 2+ concentration within the ER lumen by increasing the Ca 2+ permeability of the ER membrane. The increased ER Ca 2+ permeability conferred by Bcl-2 would be compatible with an ion channel function of Bcl-2 at the level of the ER membrane. |
| Databáze: | OpenAIRE |
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