Reduced Loading of Intracellular Ca2+ Stores and Downregulation of Capacitative Ca2+ Influx In Bcl-2-Overexpressing Cells (original) (raw)

2000, The Journal of Cell Biology

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 Ca 2 ϩ -sensitive photoprotein, aequorin, to investigate in detail the effect of Bcl-2 overexpression on intracellular Ca 2 ϩ homeostasis. In the ER and the Golgi apparatus, Bcl-2 overexpression increases the Ca 2 ϩ leak (while leaving Ca 2 ϩ accumulation unaffected), hence reducing the steady-state [Ca 2 ϩ ] levels. As a direct consequence, the [Ca 2 ϩ ] 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 Ca 2 ϩ influx activated by Ca 2 ϩ store depletion, possibly by an adaptive downregulation of this pathway. By interfering with Ca 2 ϩ -dependent events at multiple intracellular sites, these effects of Bcl-2 on intracellular Ca 2 ϩ homeostasis may contribute to the protective role of this oncogene against programed cell death.

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