Gerasimenko, Julia Vladimirovna  ORCID: https://orcid.org/0000-0002-2262-2543, Ferdek, Pawel, Fischer, Lars, Gukovskaya, Anna and Pandol, Stephen
2010.
Inhibitors of Bcl-2 protein family deplete ER Ca2+ stores in pancreatic acinar cells.
Pflugers Archiv-European Journal of Physiology
460
(5)
, pp. 891-900.
10.1007/s00424-010-0859-4
|
Abstract
Physiological stimulation of pancreatic acinar cells by cholecystokinin and acetylcholine activate a spatial-temporal pattern of cytosolic [Ca+2] changes that are regulated by a coordinated response of inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs) and calcium-induced calcium release (CICR). For the present study, we designed experiments to determine the potential role of Bcl-2 proteins in these patterns of cytosolic [Ca+2] responses. We used small molecule inhibitors that disrupt the interactions between prosurvival Bcl-2 proteins (i.e. Bcl-2 and Bcl-xl) and proapoptotic Bcl-2 proteins (i.e. Bax) and fluorescence microfluorimetry techniques to measure both cytosolic [Ca+2] and endoplasmic reticulum [Ca+2]. We found that the inhibitors of Bcl-2 protein interactions caused a slow and complete release of intracellular agonist-sensitive stores of calcium. The release was attenuated by inhibitors of IP3Rs and RyRs and substantially reduced by strong [Ca2+] buffering. Inhibition of IP3Rs and RyRs also dramatically reduced activation of apoptosis by BH3I-2′. CICR induced by different doses of BH3I-2′ in Bcl-2 overexpressing cells was markedly decreased compared with control. The results suggest that Bcl-2 proteins regulate calcium release from the intracellular stores and suggest that the spatial-temporal patterns of agonist-stimulated cytosolic [Ca+2] changes are regulated by differential cellular distribution of interacting pairs of prosurvival and proapoptotic Bcl-2 proteins.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences |
| Subjects: | Q Science > Q Science (General) Q Science > QP Physiology |
| Uncontrolled Keywords: | pancreas; pancreatic acinar cell; acetylcholine; transport; signal transduction; cell death |
| Publisher: | Springer |
| ISSN: | 0031-6768 |
| Last Modified: | 19 Oct 2022 08:40 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/18655 |
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