Inhibition of neuronal cell death after retinoic acid-induced down-regulation of P2X7 nucleotide receptor expression.
Inhibition of neuronal cell death after retinoic acid-induced down-regulation of P2X7 nucleotide receptor expression.
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DOI：
10.1007/s11010-009-0288-x
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发表时间：
2010-04
影响因子：
4.3
通讯作者：
Gonzalez, Fernando A.
中科院分区：
文献类型：
--
作者：
Orellano, Elsie A.;Rivera, Omayra J.;Chevres, Migdalia;Chorna, Nataliya E.;Gonzalez, Fernando A.
关键词：
Apoptosis is a major mechanism for cell death in the nervous system during development. P2X7 nucleotide receptors are ionotropic ATP receptors that mediate cell death under pathological conditions. We developed an in vitro protocol to investigate the expression and functional responses of P2X7 nucleotide receptors during retinoic acid (RA)-induced neuronal differentiation of human SH-SY5Y neuroblastoma cells. Neuronal differentiation was examined measuring cellular growth arrest and neuritic processes elongation. We found that SH-SY5Y cells treated for 5 days with RA under low serum content exhibited a neuron-like phenotype with neurites extending more than twice the length of the cell body and cell growth arrest. Concurrently, we detected the abolishment of intracellular-free calcium mobilization and the down-regulation of P2X7 nucleotide receptor protein expression that protected differentiated cells from neuronal cell death and reduced caspase-3 cleavage-induced by P2X7 nucleotide receptor agonist. The role of P2X7 nucleotide receptors in neuronal death was established by selectively antagonizing the receptor with KN-62 prior to its activation. We assessed the involvement of protein kinases and found that p38 signaling was activated in undifferentiated after nucleotide stimulation, but abolished by the differentiating RA pretreatment. Importantly, P2X7 receptor-induced caspase-3 cleavage was blocked by the p38 protein kinase specific inhibitor PD169316. Taken together, our results suggest that RA treatment of human SH-SY5Y cells leads to decreased P2X7 nucleotide receptor protein expression thus protecting differentiated cells from extracellular nucleotide-induced neuronal death, and p38 signaling pathway is critically involved in this protection of RA-differentiated cells.
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影响因子：
4.4
作者：
Charles, I;Khalyfa, A;Agarwal, N
通讯作者：
Agarwal, N
影响因子：
4.7
作者：
Burgos, Michelle;Neary, Joseph T.;Gonzalez, Fernando A.
通讯作者：
Gonzalez, Fernando A.
影响因子：
3.3
作者：
Franke, H;Grosche, J;Illes, P
通讯作者：
Illes, P
影响因子：
4
作者：
Diaz-Hernandez, Miguel;del Puerto, Ana;Miras-Portugal, Maria Teresa
通讯作者：
Miras-Portugal, Maria Teresa
DOI：
10.1006/scel.1994.1015
发表时间：
1994-01-01
期刊：
Seminars in Cell Biology
影响因子：
--
作者：
Chambon, Pierre
通讯作者：
Chambon, Pierre