Mechanism of alcohol-induced oxidative stress and neuronal injury
| Autor: | Brenda Morsey, James Haorah, Yuri Persidsky, Nicholas A. Floreani, Servio H. Ramirez, Santhi Gorantla |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Xanthine Oxidase
Transcription Genetic Cell Survival Poison control Gene Expression Acetaldehyde medicine.disease_cause Nitric Oxide Biochemistry Polymerase Chain Reaction Article Nitric oxide chemistry.chemical_compound Physiology (medical) medicine Humans RNA Messenger Xanthine oxidase Neuroinflammation Cells Cultured chemistry.chemical_classification Neurons Reactive oxygen species Aldehydes Analysis of Variance biology Ethanol Neurodegeneration Alcohol Dehydrogenase Cytochrome P-450 CYP2E1 medicine.disease Immunohistochemistry Cell biology Nitric oxide synthase Oxidative Stress chemistry biology.protein Nitric Oxide Synthase Reactive Oxygen Species Oxidative stress NADP |
| Zdroj: | Free radical biologymedicine. 45(11) |
| ISSN: | 0891-5849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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