Neuregulin-1α and β isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro

Gregory M. Cote, Thomas A. Miller, Nathan K LeBrasseur, Yukio Kuramochi, Douglas B. Sawyer

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Neuregulins (NRGs) are a family of alternatively spliced growth factors that act through receptor tyrosine kinases of the epidermal growth factor (EGF) receptor family in diverse tissues. The NRG-erbB signaling axis is a critical mediator of cardiac development, and growing evidence supports a role for this system in the intricate cross-talk between the microvascular endothelium and myocytes in the adult heart. The purpose of this study was first to examine the expression of splice variants of the NRG1 gene in adult rat cardiac microvascular endothelial cells and second to compare the function of these variants in cardiac myocytes. We demonstrate that cardiac microvascular endothelial cells in rat culture express multiple Type I NRG1 gene products, including both α and β variants. Comparison of the activity of recombinant NRG1α and NRG1β EGF-like domain proteins in cardiac myocytes shows that the β ligand is a more potent activator of receptor phosphorylation and intracellular signaling than the α ligand, and only the β ligand stimulated glucose uptake and protein synthesis in these culture conditions. Thus, cardiac microvascular endothelial cells express multiple NRG1 isotypes, but only β-variants are biologically active on cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalExperimental Cell Research
Volume311
Issue number1
DOIs
StatePublished - Nov 15 2005
Externally publishedYes

Fingerprint

Neuregulin-1
Neuregulins
Cardiac Myocytes
Protein Isoforms
Endothelial Cells
Ligands
Epidermal Growth Factor Receptor
Muscle Cells
Genes
Endothelium
Intercellular Signaling Peptides and Proteins
Phosphorylation
Glucose
In Vitro Techniques
Proteins

Keywords

  • Cardiac microvascular endothelial cell
  • Cardiac myocyte
  • erbB2
  • Neuregulin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Neuregulin-1α and β isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro. / Cote, Gregory M.; Miller, Thomas A.; LeBrasseur, Nathan K; Kuramochi, Yukio; Sawyer, Douglas B.

In: Experimental Cell Research, Vol. 311, No. 1, 15.11.2005, p. 135-146.

Research output: Contribution to journalArticle

Cote, Gregory M. ; Miller, Thomas A. ; LeBrasseur, Nathan K ; Kuramochi, Yukio ; Sawyer, Douglas B. / Neuregulin-1α and β isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro. In: Experimental Cell Research. 2005 ; Vol. 311, No. 1. pp. 135-146.
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