Neuregulin1 Attenuates H(2)O(2)-Induced Reductions in EAAC1 Protein Levels and Reduces H(2)O(2)-Induced Oxidative Stress.

Neuregulin1 Attenuates H(2)O(2)-Induced Reductions in EAAC1 Protein Levels and Reduces H(2)O(2)-Induced Oxidative Stress.
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DOI:
10.1007/s12640-018-9965-4
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发表时间:
2019-03
影响因子:
3.7
通讯作者:
Woo RS
Woo RS
中科院分区:
医学3区
文献类型:
--
作者:
Lee JH;Yoo JY;Kim HB;Yoo HI;Song DY;Min SS;Baik TK;Woo RS

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神经调节蛋白1(NRG 1)具有强大的神经保护特性。本研究旨在探讨NRG 1对H2O2诱导的原代大鼠皮层神经元氧化应激的抗氧化作用及其机制。Western blotting和免疫细胞化学法检测兴奋性氨基酸载体1(EAAC 1)蛋白的表达水平。测定乳酸脱氢酶(LDH)释放水平、活性氧(ROS)产生水平、超氧化物歧化酶(SOD)活性、GPx活性和线粒体膜电位(线粒体膜电位),以检查原代大鼠皮层神经元中的细胞死亡和NRG 1的抗氧化特性。H2O2以剂量依赖性方式降低EAAC1的表达。我们发现,NRG 1预处理减弱了H2O2诱导的EAAC 1表达减少。此外,NRG 1还能减少H2O2诱导的细胞死亡和氧化应激。此外,NRG1衰减H2O2诱导的抗氧化酶活性和抗氧化酶活性的降低。我们的数据表明NRG 1通过调节EAAC 1在保护免受氧化应激中的作用。这些观察结果可能为氧化应激过程中NRG 1活性的机制提供新的见解,并可能揭示调节与各种神经系统疾病相关的氧化应激的新的治疗靶点。
Neuregulin 1 (NRG1) exhibits potent neuroprotective properties. The aim of the present study was to investigate the antioxidative effects and underlying mechanisms of NRG1 against H2O2-induced oxidative stress in primary rat cortical neurons. The expression level of the excitatory amino acid carrier 1 (EAAC1) protein was measured by Western blotting and immunocytochemistry. The levels of lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity, GPx activity, and mitochondrial membrane potential (∆ψm) were determined to examine cell death and the antioxidant properties of NRG1 in primary rat cortical neurons. H2O2 reduced the expression of EAAC1 in a dose-dependent manner. We found that pretreatment with NRG1 attenuated the H2O2-induced reduction in EAAC1 expression. Moreover, NRG1 reduced the cell death and oxidative stress induced by H2O2. In addition, NRG1 attenuated H2O2-induced reductions in antioxidant enzyme activity and ∆ψm. Our data indicate a role for NRG1 in protecting against oxidative stress via the regulation of EAAC1. These observations may provide novel insights into the mechanisms of NRG1 activity during oxidative stress and may reveal new therapeutic targets for regulating the oxidative stress associated with various neurological diseases.
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