Differential expression of 14-3-3 isoforms in human alcoholic brain

Alcohol Clin Exp Res. 2011 Jun;35(6):1041-9. doi: 10.1111/j.1530-0277.2011.01436.x. Epub 2011 Feb 17.

Abstract

Background: Neuropathological damage as a result of chronic alcohol abuse often results in the impairment of cognitive function. The damage is particularly marked in the frontal cortex. The 14-3-3 protein family consists of 7 proteins, β, γ, ε, ζ, η, θ, and σ, encoded by 7 distinct genes. They are highly conserved molecular chaperones with roles in the regulation of metabolism, signal transduction, cell-cycle control, protein trafficking, and apoptosis. They may also play an important role in neurodegeneration in chronic alcoholism.

Methods: We used real-time PCR to measure the expression of 14-3-3 mRNA transcripts in both the dorsolateral prefrontal cortex and motor cortex of human brains obtained at autopsy.

Results: We found significantly lower 14-3-3β, γ, and θ expression in both cortical areas of alcoholics, but no difference in 14-3-3η expression, and higher expression of 14-3-3σ in both areas. Levels of 14-3-3ζ and ε transcripts were significantly lower only in alcoholic motor cortex.

Conclusions: Altered 14-3-3 expression could contribute to synaptic dysfunction and altered neurotransmission in chronic alcohol misuse by human subjects.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 14-3-3 Proteins / biosynthesis*
  • 14-3-3 Proteins / genetics
  • Alcoholism / genetics
  • Alcoholism / metabolism*
  • Alcoholism / physiopathology
  • Brain / metabolism
  • Brain / physiopathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / metabolism*
  • Motor Cortex / physiopathology
  • Neural Pathways / physiopathology
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiopathology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Synaptic Transmission / genetics

Substances

  • 14-3-3 Proteins
  • Protein Isoforms