cMyBP-C was decreased via KLHL3-mediated proteasomal degradation in congenital heart diseases.

Cardiac myosin binding protein C (cMyBP-C) is a cardiac structural and regulatory protein; mutations of cMyBP-C are frequently associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Cardiac special transcription factors may regulate the expression of cMyBP-C. However, the role of cMyBP-C in congenital heart diseases (CHD) remains poorly understood. ...
In the current study, western blotting and the MRM approach showed that cMyBP-C expression was significantly reduced in fetuses with CHD compared to those without. Furthermore, we found that cMyBP-C interacted with KLHL3 by immunoprecipitation and immunofluorescence, and the degradation of cMyBP-C was caused by KLHL3-mediated ubiquitination. In addition, homocysteine (Hcy, a risk factor of CHD) treatment caused a decrease in cMyBP-C and an increase in KLHL3 expression, and the proteasome inhibitor MG132 reversed the Hcy-induced reduction of cMyBP-C expression. Finally, we verified that reduced cMyBP-C by Hcy promoted apoptosis in cardiomyocytes. These results demonstrate that Hcy decreases the expression of cMyBP-C through a KLHL3-mediated ubiquitin-proteasome pathway, and thereby influences heart development.
Mesh Terms:
Animals, Carrier Proteins, Cells, Cultured, Female, Heart Defects, Congenital, Homocysteine, Humans, Pregnancy, Proteasome Endopeptidase Complex, Rats
Exp. Cell Res.
Date: Dec. 01, 2016
Download Curated Data For This Publication
207416
Switch View:
  • Interactions 2