Apolipoprotein E protects against oxidative stress in mixed neuronal-glial cell cultures by reducing glutamate toxicity
Apolipoprotein E protects against oxidative stress in mixed neuronal-glial cell cultures by reducing glutamate toxicity
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DOI：
10.1016/s0197-0186(03)00112-8
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Pearlstein, RD
中科院分区：
文献类型：
--
作者：
Lee, Y;Aono, M;Pearlstein, RD
载脂蛋白E （ApoE）缺乏已被证明对短暂性脑缺血和头部创伤后的预后有不利影响。由于氧化应激有助于这些损伤，ApoE减少不可逆氧化损伤的能力在初级混合神经元-胶质细胞培养中进行了研究。将细胞（13-16 d）暴露于50 muM过氧化氢（H2O2）中30 min，暴露24 h后通过乳酸脱氢酶（LDH）的释放来测定毒性。重组人ApoE2（100,300或1000 nM）存在于培养基中，可以部分保护细胞免受氧化损伤。这种保护作用不会被受体相关蛋白预处理逆转。NMDA受体拮抗剂MK-801也对H2O2毒性提供部分保护。保护程度与ApoE处理所赋予的保护程度相似。ApoE与MK-801的保护作用不具有相加性；在暴露于H2O2之前，用MK-801处理的培养物没有观察到ApoE保护。ApoE处理对H2O2刺激的谷氨酸释放没有影响，但在H2O2处理的培养物中，通过高亲和力谷氨酸转运体增加了谷氨酸的摄取率。用ApoE预处理也对谷氨酸诱导的LDH释放具有部分保护作用。综上所述，这些发现表明ApoE通过减少继发性谷氨酸兴奋毒性来保护混合神经元-胶质细胞培养物免受H2O2的不可逆氧化损伤。2003爱思唯尔科学有限公司版权所有。
Apolipoprotein E (ApoE) deficiency has been shown to adversely affect outcome after transient cerebral ischemia and head trauma. Since oxidative stress contributes to these injuries, the ability of ApoE to reduce irreversible oxidative damage was studied in primary mixed neuronal-glial cell cultures. Cells (13-16 days in vitro) were exposed to 50 muM hydrogen peroxide (H2O2) for 30 min, and toxicity was determined by the release of lactate dehydrogenase (LDH) 24 h after exposure. The presence of recombinant human ApoE2 (100, 300, or 1000 nM) in the culture media partially protected against oxidative injury. This protection was not reversed by pre-treatment with receptor associated protein. The NMDA receptor antagonist, MK-801, also provided partial protection against H2O2 toxicity. The degree of protection was similar to that conferred by ApoE treatment. The protective effects of ApoE and MK-801 were not additive; no ApoE protection was observed in cultures treated with MK-801 prior to H2O2 exposure. ApoE treatment had no effect on H2O2 stimulated glutamate release, but did increase the rate of glutamate uptake via the high affinity glutamate transporter in H2O2 treated cultures. Pre-treatment with ApoE also conferred partial protection against glutamate-induced LDH release. Taken together, these findings suggest that ApoE protects mixed neuronal-glial cell cultures against irreversible oxidative injury from H2O2 by reducing secondary glutamate excitotoxicity. (C) 2003 Elsevier Science Ltd. All rights reserved.