Mechanism of alcohol-induced oxidative stress and neuronal injury

James Haorah, Servio H. Ramirez, Nicholas Floreani, Santhi Gorantla, Brenda Morsey, Yuri Persidsky

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1542-1550
Number of pages9
JournalFree Radical Biology and Medicine
Volume45
Issue number11
DOIs
StatePublished - Dec 1 2008

Fingerprint

Oxidative stress
Reactive Oxygen Species
Oxidative Stress
Alcohols
Nitric Oxide Synthase
Neurons
Wounds and Injuries
Nitric Oxide
Cytochrome P-450 CYP2E1
Mitochondria
Intermediate Filaments
Acetaldehyde
Xanthine Oxidase
Alcohol Dehydrogenase
NADPH Oxidase
Alcoholics
Nervous System Diseases
Metabolism
Lipid Peroxidation
Alcoholism

Keywords

  • Alcohol dehydrogenase
  • Cytochrome P450-2E1
  • Free radicals
  • Human neurons
  • NADPH/xanthine oxidase
  • Neuronal nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Mechanism of alcohol-induced oxidative stress and neuronal injury. / Haorah, James; Ramirez, Servio H.; Floreani, Nicholas; Gorantla, Santhi; Morsey, Brenda; Persidsky, Yuri.

In: Free Radical Biology and Medicine, Vol. 45, No. 11, 01.12.2008, p. 1542-1550.

Research output: Contribution to journalArticle

Haorah, James ; Ramirez, Servio H. ; Floreani, Nicholas ; Gorantla, Santhi ; Morsey, Brenda ; Persidsky, Yuri. / Mechanism of alcohol-induced oxidative stress and neuronal injury. In: Free Radical Biology and Medicine. 2008 ; Vol. 45, No. 11. pp. 1542-1550.
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