Opposing effects of P2X(7) and P2Y purine/pyrimidine-preferring receptors on proliferation of astrocytes induced by fibroblast growth factor-2: implications for CNS development, injury, and repair.
Opposing effects of P2X(7) and P2Y purine/pyrimidine-preferring receptors on proliferation of astrocytes induced by fibroblast growth factor-2: implications for CNS development, injury, and repair.
复制标题
DOI：
10.1002/jnr.21765
复制
发表时间：
2008-11-01
影响因子：
4.2
通讯作者：
Tran, Minh D.
中科院分区：
文献类型：
--
作者：
Neary, Joseph T.;Shi, You-Fang;Kang, Yuan;Tran, Minh D.
Extracellular nucleotides play important trophic roles in development and CNS injury but functions of distinct purinergic receptors and related signaling pathways have not been fully elucidated. Here we have identified opposing effects of P2X and P2Y receptors on the ability of FGF2 to induce proliferation in primary cultures of rat cortical astrocytes. Low concentrations of ATP enhanced DNA synthesis induced by FGF2 whereas high concentrations inhibited FGF2-induced proliferation. Comparison of concentration-response experiments with ATP and 2’,3’-O-(4-benzoyl)-benzoyl-ATP (BzATP) indicated that the inhibitory effect was mediated by P2X7 receptors. Interestingly, activation of P2X7 receptors led to a state of reversible growth arrest, rather than cell death. Selectivity studies showed that proliferation evoked by epidermal growth factor and platelet-derived growth factor was also inhibited by P2X7 receptors, but P2X1 or P2X3 receptors did not inhibit proliferation induced by FGF2. A marker of mitosis, phosphohistone-3, was reduced by BzATP and increased by UTP, suggesting the enhancing effect of ATP on FGF2-induced proliferation was mediated by P2 purine/pyrimidine receptors. Phosphorylation of growth arrest-related protein kinases p38/MAPK and SAPK/JNK was strongly increased by BzATP but only weakly affected by UTP. We conclude that P2Y purine/pyrimidine receptors enhance proliferation induced by FGF2 in astrocytes whereas stimulation of P2X7 receptors inhibits proliferation by shifting cells to a state of reversible growth arrest which may be mediated by protein kinase signaling. These trophic actions of P2X7 and P2Y purine/pyrimidine receptors may contribute to the regulation of CNS development, adult neurogenesis and the response of astrocytes to injury.
登录
查看更多内容
影响因子：
4.7
作者：
Ahmed, SM;Rzigalinski, BA;Ellis, EF
通讯作者：
Ellis, EF
影响因子：
7.3
作者：
Franke, H;Krügel, U;Illes, P
通讯作者：
Illes, P
影响因子：
3.3
作者：
ABBRACCHIO, MP;SAFFREY, MJ;BURNSTOCK, G
通讯作者：
BURNSTOCK, G
影响因子：
7.3
作者：
King, BF;Liu, M;Burnstock, G
通讯作者：
Burnstock, G
影响因子：
2.5
作者：
Cheung, KK;Burnstock, G
通讯作者：
Burnstock, G