Mechanism of alcohol-induced oxidative stress and neuronal injury.
Mechanism of alcohol-induced oxidative stress and neuronal injury.
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DOI：
10.1016/j.freeradbiomed.2008.08.030
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发表时间：
2008-12-01
影响因子：
7.4
通讯作者：
Persidsky, Yuri
中科院分区：
文献类型：
--
作者：
Haorah, James;Ramirez, Servio H.;Floreani, Nicholas;Gorantla, Santhi;Morsey, Brenda;Persidsky, Yuri
关键词：
酗酒者的神经认知缺陷、神经元损伤和神经退行性变已被充分证实，但其潜在机制仍不清楚。线粒体和细胞蛋白质的氧化损伤与酒精滥用引起的神经炎症和神经系统疾病的进展交织在一起。在这里，我们提出的证据表明，乙醇脱氢酶（ADH）或细胞色素P450- 2 E1（CYP 2 E1）在原代人类神经元代谢乙醇产生活性氧（ROS）和一氧化氮（NO）通过诱导NADPH/黄嘌呤氧化酶（NOX/XOX）和一氧化氮合酶（NOS）在人类神经元。乙酰丙酮酸介导的NOX、XOX或NOS活性的增加作为转录而非翻译过程被调节。脂质过氧化产物（4-羟基壬烯醛）的显着增加和活性氧产生的增加与神经元活力下降和神经元标记物（神经丝）表达减少相一致。ROS和NO检测的新的定量方法有助于剖析酒精诱导的神经退行性变的机制。揭示氧化性神经元损伤的基本机制将成为开发新疗法的基础。
Neuro-cognitive deficits, neuronal injury, and neurodegeneration are well documented in alcoholics, yet the underlying mechanisms remain elusive. Oxidative damage of mitochondria and cellular proteins intertwines with the progression of neuroinflammation and neurological disorders initiated by alcohol abuse. Here, we present the evidence that metabolism of ethanol in primary human neurons by alcohol dehydrogenase (ADH) or cytochrome P450-2E1 (CYP2E1) generates reactive oxygen species (ROS) and nitric oxide (NO) via induction of NADPH/xanthine oxidase (NOX/XOX) and nitric oxide synthase (NOS) in human neurons. The acetaldehyde-mediated increase in NOX, XOX, or NOS activity is regulated as a transcriptional rather than a translational process. Marked increase in the lipid peroxidation product (4-hydroxynonenal) and enhanced ROS generation coincides with decreased neuronal viability and diminished expression of neuronal marker (neurofilaments). Novel quantitative methods of ROS and NO detection help dissect the mechanisms of alcohol-induced neurodegeneration. Uncovering the basic mechanisms of oxidative neuronal injury will serve as the basis for development of new therapies.
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影响因子：
3.9
作者：
CLEMENS, DL;HALGARD, CM;TUMA, DJ
通讯作者：
TUMA, DJ
影响因子：
4.7
作者：
Haorah, James;Knipe, Bryan;Persidsky, Yuri
通讯作者：
Persidsky, Yuri
影响因子：
4.8
作者：
Bai, JX;Cederbaum, AI
通讯作者：
Cederbaum, AI
DOI：
10.1097/01.alc.0000189274.00479.62
发表时间：
2005-11-01
影响因子：
3.2
作者：
Kohgo, Y;Ohtake, T;Kato, J
通讯作者：
Kato, J
影响因子：
4.7
作者：
Adermark, Louise;Lovinger, David M.
通讯作者：
Lovinger, David M.