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Involvement of P38 MAP kinase in P2X 7 receptor‐dependent cell death
Author(s) -
DiazPimentel J. A.,
Vivas P.,
Weisman G.,
Gonzalez F. A.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.19_6.x
Subject(s) - programmed cell death , microbiology and biotechnology , microglia , receptor , depolarization , p38 mitogen activated protein kinases , mapk/erk pathway , apoptosis , biology , ion channel , mitogen activated protein kinase , kinase , chemistry , biophysics , biochemistry , inflammation , immunology
The P2X 7 nucleotide receptor is a non‐selective ligand‐gated ion channel expressed primarily in hematopoietic cells, astrocytes, microglia, parotid acinar cells, and fibroblasts. P2X 7 activation opens a channel, which triggers rapid depolarization and calcium influx. Additionally, it induces the formation of non‐selective pores able to pass molecules up to 900 Da, a phenomenon not observed in any other P2X receptors. Activation of the P2X 7 receptor can lead to apoptosis or necrosis in a variety of cells including lymphocytes and microglia, but the biochemical steps linking channel/pore formation to cell death are poorly understood. Here we described the channel/pore formation upon P2X 7 receptor activation in human promyelocitic HL‐60 and human 1321N1 astrocytoma cells. In addition we found that exposure of these cells to BzATP (10 min) was sufficient to trigger activation of p38 MAP Kinase. Our results show that BzATP activate p38 MAPK pathway and that the profile of activation is characterized by a strong and transient activation of this kinase. Pretreatment of the cells with the specific inhibitor of p38 MAPK, SB203580, inhibit BzATP‐dependent LDH liberation associated with necrotic cell death. We conclude that p38 MAPK activation is involved in the pathway conducing to the P2X 7 ‐dependent necrotic cell death, and corroborate other observations that necrosis is not a passive form of cell death.