期刊
NEUROTOXICITY RESEARCH
卷 15, 期 3, 页码 193-204出版社
SPRINGER
DOI: 10.1007/s12640-009-9020-6
关键词
Neuroprotection; Nucleotide receptors; Granule neurons; GSK-3; P2X(7) receptors
资金
- Spanish Ministry of Education and Science [BFU20050207079]
- Fundacion La Caixa [BM05-114-0]
- Fundacion Marcelino Botin
In this study we report the coupling of nucleotide receptors to GSK-3 signalling, a relevant survival pathway in cerebellar granule neurons. P2X(7) agonist BzATP induced a 3-4-fold increase in GSK-3 phosphorylation, which is reported to be associated with the catalytic activity inhibition. This effect was dependent on extracellular calcium and PKC, and independent of PI3-K (phosphatidyl-inositol-3-kinase)/Akt, the main survival route of neurotrophins. BzATP also prevented the apoptosis of granule neurons induced by the pharmacological inhibition of the PI3-K signalling. Both effects, BzATP-mediated GSK-3 phosphorylation and neuroprotection, were abolished by P2X(7) receptor antagonists, BBG, PPADS and A-438079. We found that BzATP prevented the progressive GSK-3 dephosphorylation and caspase-3 activation occurring under conditions of sustained PI3-K inhibition. These results reveal that P2X(7) receptor activation could provide a relevant survival route alternative to classical neurotrophic factors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据