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

Yun You Li, M. I. Zhibao, Yiqin Feng, Charles F. Mctiernan, Renping Zhou, Paul D. Robbins, Simon C. Watkins, Arthur M. Feldman

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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-A5α) and a 27-amino acid deletion form (ephrin-A5β) were isolated. To examine the role of ephrin-A5 in cardiomyocytes, the cDNAs were inserted into adenoviral vectors, termed Ad.ephrin-A5α and Ad.ephrin-A5Β, 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-A5α and ephrin-A5β downregulated cyclin D2, cyclin-dependent kinase-4 proteins, and their cognate receptor EphA3, which were associated with reduced bromodeoxyuridine incorporation in cardiomyocytes. Whereas ephrin-A5α and ephrin-A5β also induced differential gene expression, only ephrin-A5β 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.

Original languageEnglish (US)
Pages (from-to)H2738-H2746
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number6 50-6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Adenoviral gene transfer
  • DNA synthesis
  • Eph receptor tyrosine kinase
  • Gene expression array

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