Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum
AUTOR(ES)
Foyouzi-Youssefi, Reyhaneh
FONTE
The National Academy of Sciences
RESUMO
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 Ca2+ storage and release by the ER. The expression of Bcl-2 decreased the amount of Ca2+ 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 Ca2+ store content in the presence of mitochondrial inhibitors, suggesting that its effects were not mediated through mitochondrial Ca2+ uptake. Direct measurements with ER-targeted Ca2+-sensitive fluorescent “cameleon” proteins revealed that Bcl-2 decreased the free Ca2+ concentration within the lumen of the ER, [Ca2+]ER. Analysis of the kinetics of Ca2+ store depletion in response to the Ca2+-ATPase inhibitor thapsigargin revealed that Bcl-2 increased the permeability of the ER membrane. These results suggest that Bcl-2 decreases the free Ca2+ concentration within the ER lumen by increasing the Ca2+ permeability of the ER membrane. The increased ER Ca2+ permeability conferred by Bcl-2 would be compatible with an ion channel function of Bcl-2 at the level of the ER membrane.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18500Documentos Relacionados
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