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Potentiation of the store-operated calcium entry (SOCE) induces phytohemagglutinin-activated Jurkat T cell apoptosis.

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.
AuthorsAlaeddine Djillani, Isabelle Doignon, Tomas Luyten, Bouchaib Lamkhioued, Sophie C Gangloff, Jan B Parys, Oliver Nüße, Christine Chomienne, Olivier Dellis
JournalCell calcium (Cell Calcium) Vol. 58 Issue 2 Pg. 171-85 (Aug 2015) ISSN: 1532-1991 [Electronic] Netherlands
PMID25963393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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