Proceedings of The Physiological Society

University College London (2011) Proc Physiol Soc 24, C02 and PC02

Oral Communications

Calcium regulation of apoptosis in pancreatic acinar cells

O. Gerasimenko1, P. Ferdek1, J. Gerasimenko1, O. H. Petersen1

1. School of Biosciences, Cardiff University, Cardiff, United Kingdom.

We have studied calcium regulation of induction of apoptosis in pancreas. In pancreatic acinar cells, the earliest events were found to be cytosolic calcium elevations due to release of calcium from intracellular stores1. As a result of that calcium levels also increased in mitochondria aiding mitochondrial depolarisation and mPTP. High mitochondrial calcium at the time of oxidant stress was found to be the crucial factor in the cell fate2. When mitochondrial calcium was low, then apoptosis did not occur regardless of other stores’ content. We also studied Bcl-2 family members, well known regulators of apoptosis involved in regulation of intracellular calcium homeostasis3. Most interesting was a potential link between Bcl-2 family proteins and a calcium induced calcium release (CICR) from the intracellular stores. Inhibition of antiapoptotic proteins induced calcium release from the ER that lead to the formation of calcium plateau while inhibition of either IP3Rs or RyRs reduced but did not abolish calcium release. Furthermore, we have shown that loss of Bcl-2 protein significantly affected calcium extrusion as well as apoptosis/necrosis ratio in pancreatic acinar cells. In conclusion we suggest that Bcl-2 regulates vast majority of main components of calcium signalling, serving its crucial role in regulation of cell death.

Where applicable, experiments conform with Society ethical requirements