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Ethanol and acetaldehyde exposure induces specific epigenetic modifications in the prodynorphin gene promoter in a human neuroblastoma cell line.

Abstract
Ethanol alters neural activity through interaction with multiple neurotransmitters and neuromodulators. The endogenous opioid system seems to play a key role, since the opioid receptor antagonist naltrexone (ReVia®) attenuates craving for alcohol. We recently reported that ethanol and acetaldehyde, the first product of ethanol metabolism, affect transcription of opioid system genes in human SH-SY5Y neuroblastoma cells. In the current study, potential epigenetic mechanisms were investigated to clarify these effects on prodynorphin gene expression. DNA methylation was analyzed by bisulfite pyrosequencing, and chromatin immunoprecipitation was used to assess putative specific histone modifications at the prodynorphin gene promoter. The results demonstrated a temporal relationship between selective chromatin modifications induced by ethanol and acetaldehyde and changes in prodynorphin gene expression quantitated by real-time qPCR. DNA methylation was not altered in any of the experimental conditions used. The epigenetic changes may precede gene transcription, and histone modifications might keep the prodynorphin gene in a poised state for later reactivation. A link has been observed between gene expression alterations and selective epigenetic modulation in the prodynorphin promoter region, demonstrating a specificity of the changes induced by ethanol and acetaldehyde. The latter may be mediating ethanol effects at the genomic level.
AuthorsClaudio D'Addario, Sofia Johansson, Sanzio Candeletti, Patrizia Romualdi, Sven Ove Ögren, Lars Terenius, Tomas J Ekström
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 25 Issue 3 Pg. 1069-75 (Mar 2011) ISSN: 1530-6860 [Electronic] United States
PMID21106935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Central Nervous System Depressants
  • Chromatin
  • Enkephalins
  • Protein Precursors
  • Ethanol
  • preproenkephalin
  • Acetaldehyde
Topics
  • Acetaldehyde (pharmacology)
  • Cell Line, Tumor
  • Central Nervous System Depressants (pharmacology)
  • Chromatin (genetics)
  • DNA Methylation (drug effects)
  • Enkephalins (genetics)
  • Epigenomics
  • Ethanol (pharmacology)
  • Gene Expression Regulation (drug effects)
  • Humans
  • Neuroblastoma
  • Promoter Regions, Genetic (physiology)
  • Protein Precursors (genetics)

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