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

Cell Calcium. 2015 Aug;58(2):171-85. doi: 10.1016/j.ceca.2015.04.005. Epub 2015 Apr 24.

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.

Keywords: Apoptosis; Calcium influx; Potentiation; Store-operated calcium entry; T-cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Boron Compounds / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / chemistry
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / 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
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • 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