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Differential effects of overexpression of two forms of ephrin-A5 on neonatal rat cardiomyocytes

Academic Article
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Overview

authors

  • Li, Yuxing
  • Mi, Z. B.
  • Feng, Yangbo
  • McTiernan, C. F.
  • Zhou, R. P.
  • Robbins, Paul D.
  • Watkins, S. C.
  • Feldman, A. M.

publication date

  • December 2001

journal

  • American Journal of Physiology-Heart and Circulatory Physiology  Journal

abstract

  • Eph receptors constitute the largest family of receptor tyrosine kinases. Multiple transcripts of ephrin-A5, the cognate ligand of the EphA3 receptor, were found in neonatal rat cardiomyocytes. Two cDNA clones encoding the full-length ephrin-A5 (ephrin-A5 alpha) and a 27-amino acid deletion form (ephrin-A5 beta) were isolated. To examine the role of ephrin-A5 in cardiomyocytes, the cDNAs were inserted into adenoviral vectors, termed Ad.ephrin-A5 alpha and Ad.ephrin-A5 beta, respectively, and overexpressed in cardiomyocytes. The effect of ephrin-A5 on cardiomyocyte gene expression was investigated using a cDNA expression array and Western blot analysis. The results showed that both ephrin-A5 alpha and ephrin-A5 beta downregulated cyclin D2, cyclin-dependent kinase-4 proteins, and their cognate receptor EphA3, which were associated with reduced bromodeoxyuridine incorporation in cardiomyocytes. Whereas ephrin-A5 alpha and ephrin-A5 beta also induced differential gene expression, only ephrin-A5 beta significantly upregulated the transcription of brain natriuretic peptide and downregulated ras-related protein RAB2, protein kinase C inhibitor protein-1, clusterin, and insulin-like growth factor-binding protein. The results suggest that the two forms of ephrin-A5 share similar function while differ in regulating different sets of genes in cardiomyocytes.

subject areas

  • Adenoviridae
  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Base Sequence
  • Cells, Cultured
  • Cyclin D2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • Cyclins
  • DNA
  • Down-Regulation
  • Ephrin-A3
  • Ephrin-A5
  • Gene Expression Regulation, Developmental
  • Gene Transfer Techniques
  • Membrane Proteins
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal
  • Myocardium
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic
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Research

keywords

  • DNA synthesis
  • Eph receptor tyrosine kinase
  • adenoviral gene transfer
  • gene expression array
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Identity

International Standard Serial Number (ISSN)

  • 0363-6135

PubMed ID

  • 11709443
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Additional Document Info

start page

  • H2738

end page

  • H2746

volume

  • 281

issue

  • 6

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