Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Mol Med Rep. 2012 May;5(5):1357-61. doi: 10.3892/mmr.2012.816. Epub 2012 Feb 29.
The purinergic P2X7 receptor (P2X7R) can be activated by ATP and plays significant and complex roles in neuropathology. However, research is limited concerning the role of P2X7R in radial glia following hypoxia-ischemia (HI). In this study, radial glial clone L2.3 cells were cultured and subjected to oxygen-glucose deprivation (OGD) to generate an HI model in vitro. We found that HI decreased P2X7R expression in the L2.3 cells. Activation of P2X7R in L2.3 cells by 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) led to cell death in a dose- and time-dependent manner, while a P2X7R antagonist, oxidized ATP (oATP), alleviated the injury induced by BzATP or HI. We also found that P2X7R modulated the phosphorylation of glycogen synthase kinase-3β (GSK-3β). The present findings suggest that L2.3 cells express P2X7R, and this receptor may be involved in HI injury of radial glia by mediating phosphorylation of GSK-3β.
嘌呤能 P2X7 受体(P2X7R)可被 ATP 激活,并在神经病理学中发挥重要且复杂的作用。然而,关于 P2X7R 在缺氧缺血(HI)后放射状胶质细胞中的作用的研究有限。在这项研究中,培养了放射状胶质克隆 L2.3 细胞,并进行氧葡萄糖剥夺(OGD)以在体外产生 HI 模型。我们发现 HI 降低了 L2.3 细胞中 P2X7R 的表达。3'-O-(4-苯甲酰基苯甲酰基)腺苷 5'-三磷酸(BzATP)激活 L2.3 细胞中的 P2X7R 会导致细胞死亡,呈剂量和时间依赖性,而 P2X7R 拮抗剂氧化型 ATP(oATP)可减轻 BzATP 或 HI 引起的损伤。我们还发现 P2X7R 调节糖原合酶激酶-3β(GSK-3β)的磷酸化。本研究结果表明,L2.3 细胞表达 P2X7R,该受体可能通过介导 GSK-3β 的磷酸化参与 HI 对放射状胶质细胞的损伤。