Photodynamic therapy leads to death of C6 glioma cells partly through AMPAR
Photodynamic therapy leads to death of C6 glioma cells partly through AMPAR
复制标题
光动力疗法部分通过 AMPAR 导致 C6 神经胶质瘤细胞死亡
DOI：
10.1016/j.brainres.2011.11.048
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发表时间：
2012-01-18
期刊：
影响因子：
2.9
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Du, Peng;Hu, ShengLi;Feng, Hua
胶质瘤细胞在生长过程中释放谷氨酸，谷氨酸促进其自身的增殖和迁移，并通过谷氨酸受体引起Ca 2+内流对周围神经元产生兴奋性毒性。然而，谷氨酸及其受体在光动力学疗法（PDT）治疗胶质瘤细胞中的作用尚不清楚。在此，我们在PDT之前对C6胶质瘤细胞施用α-氨基-3-羟基-5-甲基-4-异恶唑丙酸谷氨酸受体（AMPAR）拮抗剂。观察PDT后C6细胞谷氨酸释放、AMPAR表达、细胞凋亡及细胞内游离钙（[Ca 2 +] i）的变化。结果发现，PDT诱导C6细胞外谷氨酸含量增加，AMPAR亚基GluR 1和GluR 2表达增加，可能是导致C6细胞内钙内流和凋亡的重要原因。加入AMPAR拮抗剂后，C6细胞内游离钙减少，凋亡率降低。结果提示PDT可能通过谷氨酸及其受体AMPAR诱导C6胶质瘤细胞内钙内流进而诱导细胞凋亡而导致细胞死亡。本研究为进一步了解光动力治疗对胶质瘤的作用及其分子机制奠定了基础。(C)2011爱思唯尔有限公司版权所有。
Glioma cells release glutamate during growth, which promotes proliferation and migration of itself and causes excitotoxicity to the surrounding neurons by Ca2+ influx through glutamate receptors. However, the role of glutamate and its receptors in the photodynamic therapy (PDT) on glioma cells is still unclear. Here we administered alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor (AMPAR) antagonist prior to PDT on C6 glioma cells. The changes of glutamate release, expression of AMPAR, apoptosis of C6 cells, and intracellular free calcium ([Ca2+](i)) were examined after PDT. We found that PDT increased extracellular glutamate and expression of AMPAR subunit GluR1 and GluR2, which might result in Ca2+ influx and apoptosis of C6 cells. When AMPAR antagonist was added, intracellular free calcium reduced and apoptosis rate of C6 cells decreased. These results indicate that PDT may lead to death of C6 glioma cells partly through glutamate and its receptors AMPAR, which induces Ca2+ influx and then cells apoptosis. This study allows us to further understand the effects and molecular mechanism of PDT on glioma. (C) 2011 Elsevier B.V. All rights reserved.