title: 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.
authors.affiliation: Univ Paris-Sud, Orsay, France; UMR-S 757 INSERM, Orsay, France.
authors.forename: Alaeddine
authors.initials: A
authors.lastname: Djillani
authors.affiliation: UMR-S 757 INSERM, Orsay, France; Univ Paris-Sud, Orsay, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Doignon
authors.affiliation: KU Leuven, Lab. Mol. Cell. Signaling, Leuven, Belgium.
authors.forename: Tomas
authors.initials: T
authors.lastname: Luyten
authors.affiliation: EA 4691, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: Bouchaib
authors.initials: B
authors.lastname: Lamkhioued
authors.affiliation: EA 4691, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Gangloff
authors.affiliation: KU Leuven, Lab. Mol. Cell. Signaling, Leuven, Belgium.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Parys
authors.affiliation: Univ Paris-Sud, Orsay, France; UMR-S 757 INSERM, Orsay, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Nüße
authors.affiliation: UMR-S 1131 INSERM, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
authors.affiliation: Univ Paris-Sud, Orsay, France; UMR-S 757 INSERM, Orsay, France. Electronic address: olivier.dellis@u-psud.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dellis
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein; D018408:Patch-Clamp Techniques; D010835:Phytohemagglutinins / Q000633:toxicity*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: C538758:2-aminoethyl diphenylborinate; D001896:Boron Compounds; D015220:Calcium Channels; D007376:Interleukin-2; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D010835:Phytohemagglutinins; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
keywords: Apoptosis; Calcium influx; Potentiation; Store-operated calcium entry; T-cell