Bax affects intracellular Ca2+ stores and induces Ca2+ wave propagation

• DOI: 10.1038/sj.cdd.4401508
• Publication Date: 2004-10-22T09:07:23Z
• Authors: A C P Carvalho; J Sharpe; T R Rosenstock; A F V Teles; A J Kowaltowski; R J Youle; S S Smaili
• Keywords: Intracellular Fluid; 0303 health sciences; Cell Respiration; Cytochromes c; Apoptosis; Intracellular Membranes; Ruthenium Red; Membrane Potentials; Mitochondria; Rats; 03 medical and health sciences; Animals, Newborn; Proto-Oncogene Proteins c-bcl-2; Astrocytes; Cyclosporine; Animals; Calcium; Calcium Signaling; Cells, Cultured; bcl-2-Associated X Protein

In the present study, we evaluated proapoptotic protein Bax on mitochondria and Ca2+ homeostasis in primary cultured astrocytes. We found that recombinant Bax (rBax, 10 and 100 ng/ml) induces a loss in mitochondrial membrane potential (Delta Psi m). This effect might be related to the inhibition of respiratory rates and a partial release of cytochrome c, which may change mitochondrial morphology. The loss of Delta Psi m and a selective permeabilization of mitochondrial membranes contribute to the release of Ca2+ from the mitochondria. This was inhibited by cyclosporin A (5 microM) and Ruthenium Red (1 microg/ml), indicating the involvement of mitochondrial Ca2+ transport mechanisms. Bax-induced mitochondrial Ca2+ release evokes Ca2+ waves and wave propagation between cells. Our results show that Bax induces mitochondrial alteration that affects Ca2+ homeostasis and signaling. These changes show that Ca2+ signals might be correlated with the proapoptotic activities of Bax.