AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation.

Area of Science:

• Cardiology
• Molecular Biology
• Cellular Physiology

Background:

• Phenylephrine (PE) induces pathological gene expression and functional decline in adult rat ventricular myocytes (ARVMs).
• Previous studies showed dominant negative c-Fos (AFos) inhibited PE-induced pathological gene profiles in neonatal myocytes.
• The role of AFos in PE-induced changes in adult myocytes remained unclear.

Purpose of the Study:

• To investigate the effect of AFos on PE-induced changes in adult rat ventricular myocytes (ARVMs).
• To determine the relationship between gene expression, cardiac growth, and myocyte function.

Main Methods:

• Adult rat ventricular myocytes were isolated and infected with adenovirus expressing beta-galactosidase (control) or AFos.
• Cells were treated with phenylephrine (PE) to induce pathological changes.
• Evaluated protein synthesis, gene expression, calcium transients, contractility, and phospholamban (PLB) phosphorylation.

Main Results:

• PE stimulated protein synthesis, pathological gene expression, and depressed contractility/calcium transients in control ARVMs.
• AFos-expressing ARVMs showed PE-induced growth but inhibited pathological gene expression and functional decline.
• AFos prevented the PE-induced decrease in phospholamban (PLB) phosphorylation at serine-16.

Conclusions:

• AFos expression inhibits pathological gene expression and preserves contractile and calcium handling functions in PE-stimulated ARVMs.
• PE-induced cardiac growth is unaffected by AFos.
• Preserved myocyte function in AFos-expressing cells is partly due to maintained PLB phosphorylation.