Abstract |
Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) entry pathway of non-excitable cells. In the past decade, the activation of this entry has been unveiled, with STIM1, a protein of the endoplasmic reticulum able to sense the intraluminal Ca(2+) content, and Orai1, the pore-forming unit of the Ca(2+) release activated Ca(2+) ( CRAC) channels. When Ca(2+) ions are released from the endoplasmic reticulum, STIM1 proteins oligomerize and directly interact with Orai1 proteins, allowing the opening of the CRAC channels and a massive Ca(2+) ion influx known as SOCE. As Ca(2+) is involved in various cellular processes, the discovery of new drugs acting on the SOCE should be of interest to control the cell activity. By testing analogs of 2-aminoethyl diphenylborinate (2-APB), a well known, though not so selective effector of the SOCE, we identified methoxy diethylborinate (MDEB), a molecule able to potentiate the SOCE in three leukocyte and two breast cancer cell lines by increasing the Ca(2+) influx amplitude. Unlike 2-APB, MDEB does not affect the Ca(2+) pumps or the Ca(2+) release from the endoplasmic reticulum. MDEB could therefore represent the first member of a new group of molecules, specifically able to potentiate SOCE. Although not toxic for non-activated Jurkat T cells, it could induce the apoptosis of phytohemagglutinin-stimulated cells.
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Authors | Alaeddine Djillani, Isabelle Doignon, Tomas Luyten, Bouchaib Lamkhioued, Sophie C Gangloff, Jan B Parys, Oliver Nüße, Christine Chomienne, Olivier Dellis |
Journal | Cell calcium
(Cell Calcium)
Vol. 58
Issue 2
Pg. 171-85
(Aug 2015)
ISSN: 1532-1991 [Electronic] Netherlands |
PMID | 25963393
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- 2-aminoethyl diphenylborinate
- Boron Compounds
- Calcium Channels
- Interleukin-2
- Membrane Proteins
- Neoplasm Proteins
- ORAI1 Protein
- ORAI1 protein, human
- Phytohemagglutinins
- RNA, Small Interfering
- STIM1 protein, human
- Stromal Interaction Molecule 1
- Calcium
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Topics |
- Apoptosis
(drug effects)
- Boron Compounds
(pharmacology)
- Calcium
(metabolism)
- Calcium Channels
(chemistry, genetics, metabolism)
- Cell Line, Tumor
- Down-Regulation
(drug effects)
- Endoplasmic Reticulum
(drug effects, metabolism)
- Humans
- Interleukin-2
(metabolism)
- Jurkat Cells
- Membrane Proteins
(metabolism)
- Neoplasm Proteins
(metabolism)
- ORAI1 Protein
- Patch-Clamp Techniques
- Phytohemagglutinins
(toxicity)
- RNA Interference
- RNA, Small Interfering
(metabolism)
- Stromal Interaction Molecule 1
- T-Lymphocytes
(cytology, drug effects, metabolism)
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