TY - JOUR
T1 - Differential effects of overexpression of two forms of ephrin-A5 on neonatal rat cardiomyocytes
AU - Li, Yun You
AU - Zhibao, M. I.
AU - Feng, Yiqin
AU - Mctiernan, Charles F.
AU - Zhou, Renping
AU - Robbins, Paul D.
AU - Watkins, Simon C.
AU - Feldman, Arthur M.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Adenoviral gene transfer
KW - DNA synthesis
KW - Eph receptor tyrosine kinase
KW - Gene expression array
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U2 - 10.1152/ajpheart.2001.281.6.h2738
DO - 10.1152/ajpheart.2001.281.6.h2738
M3 - Article
C2 - 11709443
AN - SCOPUS:0035658777
SN - 0363-6135
VL - 281
SP - H2738-H2746
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 50-6
ER -