A novel role for Bcl-2 in regulation of cellular calcium extrusion.

Abstract

The antiapoptotic protein Bcl-2 plays important roles in Ca(2+) signaling by influencing inositol triphosphate receptors and regulating Ca(2+)-induced Ca(2+) release. Here we investigated whether Bcl-2 affects Ca(2+) extrusion in pancreatic acinar cells. We specifically blocked the Ca(2+) pumps in the endoplasmic reticulum and assessed the rate at which the cells reduced an elevated cytosolic Ca(2+) concentration after a period of enhanced Ca(2+) entry. Because external Ca(2+) was removed and endoplasmic reticulum Ca(2+) pumps were blocked, Ca(2+) extrusion was the only process responsible for recovery. Cells lacking Bcl-2 restored the basal cytosolic Ca(2+) level much faster than control cells. The enhanced Ca(2+) extrusion in cells from Bcl-2 knockout (Bcl-2 KO) mice was not due to increased Na(+)/Ca(2+) exchange activity, because removal of external Na(+) did not influence the Ca(2+) extrusion rate. Overexpression of Bcl-2 in the pancreatic acinar cell line AR42J decreased Ca(2+) extrusion, whereas silencing Bcl-2 expression (siRNA) had the opposite effect. Loss of Bcl-2, while increasing Ca(2+) extrusion, dramatically decreased necrosis and promoted apoptosis induced by oxidative stress, whereas specific inhibition of Ca(2+) pumps in the plasma membrane (PMCA) with caloxin 3A1 reduced Ca(2+) extrusion and increased necrosis. Bcl-2 regulates PMCA function in pancreatic acinar cells and thereby influences cell fate.

• Authors: Pawel E Ferdek, Julia V Gerasimenko, Shuang Peng, Alexei V Tepikin, Ole H Petersen, Oleg V Gerasimenko
• Journal: Current biology : CB (Curr Biol) Vol. 22 Issue 13 Pg. 1241-6 (Jul 10 2012) ISSN: 1879-0445 [Electronic] England
• PMID: 22704985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Inositol 1,4,5-Trisphosphate Receptors
• Peptides
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• caloxin 3A1
• Bcl2 protein, mouse
• Barium
• Meglumine
• Vitamin K 3
• Ca(2+) Mg(2+)-ATPase
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Calcium

Topics

• Acinar Cells (drug effects, metabolism)
• Animals
• Apoptosis (genetics)
• Barium (metabolism)
• Ca(2+) Mg(2+)-ATPase (antagonists & inhibitors)
• Calcium (metabolism)
• Calcium Signaling
• Cell Membrane (drug effects, metabolism)
• Cytosol (metabolism)
• Endoplasmic Reticulum (drug effects, metabolism)
• Inositol 1,4,5-Trisphosphate Receptors (metabolism)
• Meglumine
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Necrosis (genetics)
• Pancreas (cytology, pathology)
• Peptides (pharmacology)
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (antagonists & inhibitors, metabolism)
• Vitamin K 3 (pharmacology)