Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 284, Issue 15, Pages 10120-10128Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M805805200
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Funding
- National Institutes of Health [1P01AG025532-01A1]
- Italian Association for Cancer Research
- Italian Space Agency
- Italian Ministry of University and Scientific Research
- Commission of European Communities 7th Framework Program [HEALTH-F2-2007-202231]
- PRRIITT program of the Emilia Romagna Region
- United Mitochondrial Disease Foundation
- University of Ferrara
- Telethon of Italy
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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 Ca2+ increase triggered by its activation. Here we show that P2X(7) transfection increased the ability of the endoplasmic reticulum to accumulate, store, and release Ca2+. This caused a larger agonist-stimulated increase in cytosol and mitochondrial Ca2+ 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 Zn2+ 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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