Journal article
A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage
Biological psychiatry (1969), Vol.67(9), pp.855-863
2010
DOI: 10.1016/j.biopsych.2009.10.032
PMID: 20022592
Abstract
Alcoholism is a major psychiatric condition at least partly associated with ethanol (EtOH)-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage.
Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of EtOH. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an EtOH diet. Coimmunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNA interference and pharmacological intervention were used, and cell damage was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) and hydrogen peroxide measurements.
Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-β-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to EtOH. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (deprenyl) and rasagiline (Azilect) can block this cascade.
Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which might play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies.
Details
- Title: Subtitle
- A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage
- Creators
- Xiao-Ming Ou - University of MississippiCraig A Stockmeier - University of MississippiHerbert Y Meltzer - Vanderbilt UniversityJames C Overholser - Case Western Reserve UniversityGeorge J Jurjus - Case Western Reserve UniversityLesa Dieter - Case Western Reserve UniversityKevin Chen - University of Southern CaliforniaDeyin Lu - University of MississippiChandra Johnson - University of MississippiMoussa B.H Youdim - Family Research InstituteMark C Austin - University of MississippiJia Luo - University of KentuckyAkira Sawa - Johns Hopkins UniversityWarren May - University of MississippiJean C Shih - University of Southern California
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.67(9), pp.855-863
- DOI
- 10.1016/j.biopsych.2009.10.032
- PMID
- 20022592
- NLM abbreviation
- Biol Psychiatry
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2010
- Academic Unit
- Pathology
- Record Identifier
- 9984186504002771
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