Neuroprotective effects of an adenoviral vector expressing the glucose transporter: a detailed description of the mediating cellular events
Neuroprotective effects of an adenoviral vector expressing the glucose transporter: a detailed description of the mediating cellular events
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DOI：
10.1016/s0006-8993(01)02572-0
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发表时间：
2001-07-20
期刊：
影响因子：
2.9
通讯作者：
Sapolsky, RM
中科院分区：
文献类型：
--
作者：
Gupta, A;Ho, DY;Sapolsky, RM
关于坏死性损伤后介导神经元死亡的事件存在相当多的知识;受此启发，现在已经成功地尝试使用基因治疗方法来保护神经元免受这种坏死性损伤。然而，在许多此类研究中，尚不清楚是什么细胞事件序列将转基因的过表达与生存增强联系起来。我们这样做，探讨过表达的谷氨酸-1葡萄糖转运蛋白与腺病毒载体在海马文化的兴奋毒素红藻氨酸（KA）的挑战的影响。这种过度表达增强葡萄糖转运，减弱ATP浓度的下降，减少兴奋性氨基酸神经递质的释放，并降低总游离胞质钙负荷。与这些有益的效果相对应，这种基因治疗干预增强了神经元存活。因此，这种特定基因疗法的神经保护作用发生在坏死性神经元损伤机制的已知框架内。(C)2001爱思唯尔科技有限公司。保留所有权利。
Considerable knowledge exists concerning the events mediating neuron death following a necrotic insult; prompted by this, there have now been successful attempts to use gene therapy approaches to protect neurons from such necrotic injury. In many such studies, however, it is not clear what sequence of cellular events connects the overexpression of the transgene with the enhanced survival. We do so, exploring the effects of overexpressing the Glut-1 glucose transporter with an adenoviral vector in hippocampal cultures challenged with the excitotoxin kainic acid (KA). Such overexpression enhanced glucose transport, attenuated the decline in ATP concentrations, decreased the release of excitatory amino acid neurotransmitters, and decreased the total free cytosolic calcium load. Commensurate with these salutary effects, neuronal survival was enhanced with this gene therapy intervention. Thus, the neuroprotective effects of this particular gene therapy occurs within the known framework of the mechanisms of necrotic neuronal injury. (C) 2001 Elsevier Science B.V. All rights reserved.