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

Ferdek, Pawel, Gerasimenko, Julia Vladimirovna ORCID: https://orcid.org/0000-0002-2262-2543, Peng, Shuang, Tepikin, Alexei V., Petersen, Ole Holger ORCID: https://orcid.org/0000-0002-6998-0380 and Gerasimenko, Oleg Vsevolodovich ORCID: https://orcid.org/0000-0003-2573-8258 2012. A novel role for Bcl-2 in regulation of cellular calcium extrusion. Current Biology 22 (13) , pp. 1241-1246. 10.1016/j.cub.2012.05.002

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Abstract

The antiapoptotic protein Bcl-2 [ [1] and [2]] plays important roles in Ca2+ signaling [3] by influencing inositol triphosphate receptors and regulating Ca2+-induced Ca2+ release [ [4], [5] and [6]]. Here we investigated whether Bcl-2 affects Ca2+ extrusion in pancreatic acinar cells. We specifically blocked the Ca2+ pumps in the endoplasmic reticulum and assessed the rate at which the cells reduced an elevated cytosolic Ca2+ concentration after a period of enhanced Ca2+ entry. Because external Ca2+ was removed and endoplasmic reticulum Ca2+ pumps were blocked, Ca2+ extrusion was the only process responsible for recovery. Cells lacking Bcl-2 restored the basal cytosolic Ca2+ level much faster than control cells. The enhanced Ca2+ extrusion in cells from Bcl-2 knockout (Bcl-2 KO) mice was not due to increased Na+/Ca2+ exchange activity, because removal of external Na+ did not influence the Ca2+ extrusion rate. Overexpression of Bcl-2 in the pancreatic acinar cell line AR42J decreased Ca2+ extrusion, whereas silencing Bcl-2 expression (siRNA) had the opposite effect. Loss of Bcl-2, while increasing Ca2+ extrusion, dramatically decreased necrosis and promoted apoptosis induced by oxidative stress, whereas specific inhibition of Ca2+ pumps in the plasma membrane (PMCA) with caloxin 3A1 reduced Ca2+ extrusion and increased necrosis. Bcl-2 regulates PMCA function in pancreatic acinar cells and thereby influences cell fate.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Publisher:	Elsevier
ISSN:	0960-9822
Funders:	MRC
Last Modified:	07 Aug 2024 22:29
URI:	https://orca.cardiff.ac.uk/id/eprint/32580

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