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Prodynorphin transcripts and proteins differentially expressed and regulated in the adult human brain

Academic Article
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Overview

authors

  • Nikoshkov, A.
  • Hurd, Y. L.
  • Yakovleva, T.
  • Bazov, I.
  • Marinova, Z.
  • Cebers, G.
  • Pasikova, N.
  • Gharibyan, A.
  • Terenius, Lars
  • Bakalkin, G.

publication date

  • 2005

journal

  • FASEB Journal  Journal

abstract

  • Transcription from multiple promoters along with alternative mRNA splicing constitutes the basis for cell-specific gene expression and mRNA and protein diversity. The prodynorphin gene (PDYN) gives rise to prodynorphin (PDYN), precursor to dynorphin opioid peptides that regulate diverse physiological functions and are implicated in various neuropsychiatric disorders. Here, we characterized PDYN transcripts and proteins in the adult human brain and studied PDYN processing and intracellular localization in model cell lines. Seven PDYN mRNAs were identified in the human brain; two of the transcripts, FL1 and FL2, encode the full-length PDYN. The dominant, FL1 transcript shows high expression in limbic-related structures such as the nucleus accumbens and amygdala. The second, FL2 transcript is only expressed in few brain structures such as the claustrum and hypothalamus. FL-PDYN was identified for the first time in the brain as the dominant PDYN protein product. Three novel PDYNs expressed from spliced or truncated PDYN transcripts either lack a central segment but are still processed into dynorphins, or are translated into N-terminally truncated proteins. One truncated PDYN is located in the cell nucleus, suggesting a novel nonopioid function for this protein. The complexity of PDYN expression and diversity of its protein products may be relevant for diverse levels of plasticity in adaptive responses for the dynorphin system.

subject areas

  • Adult
  • Animals
  • Brain
  • Cells, Cultured
  • Enkephalins
  • Exons
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Promoter Regions, Genetic
  • Protein Biosynthesis
  • Protein Precursors
  • Protein Processing, Post-Translational
  • RNA, Messenger
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Research

keywords

  • alternative transcripts
  • kappa-opioid receptor
  • opioid peptides
  • preprodynorphin
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Identity

International Standard Serial Number (ISSN)

  • 0892-6638

Digital Object Identifier (DOI)

  • 10.1096/fj.05-3743fje

PubMed ID

  • 16014400
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Additional Document Info

start page

  • 1543

end page

  • 5

volume

  • 19

issue

  • 9

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