Expression of the P2X7 Receptor Increases the Ca2+ Content of the Endoplasmic Reticulum, Activates NFATc1, and Protects from Apoptosis

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Feb 11

PMID 19204004

Citations 53

Authors

Elena Adinolfi

Maria Giulia Callegari

Maria Cirillo

Paolo Pinton

Carlotta Giorgi

Dario Cavagna

Rosario Rizzuto

Francesco Di Virgilio

Affiliations

Soon will be listed here.

Abstract

The P2X(7) receptor is known for the cytotoxic activity because of its ability to cause opening of non-selective pores in the plasma membrane and activate apoptotic caspases. A key factor of P2X(7)-dependent cytotoxicity is the massive intracellular Ca(2+) increase triggered by its activation. Here we show that P2X(7) transfection increased the ability of the endoplasmic reticulum to accumulate, store, and release Ca(2+). This caused a larger agonist-stimulated increase in cytosol and mitochondrial Ca(2+) in P2X(7) transfectants than in mock transfected cells. P2X(7) transfectants survived and even proliferated in serum-free conditions and were resistant to apoptosis triggered by ceramide, staurosporin, or intracellular Zn(2+) chelation. Finally, the nuclear factor of activated T cells complex 1 (NFATc1) was strongly activated in the P2X(7) transfectants. These observations support our previous finding that the P2X(7) receptor under tonic conditions of stimulation, i.e. those observed in response to basal ATP release, has an anti-apoptotic or even growth promoting rather than cytotoxic activity.

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