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
Animals, Carrier Proteins, Cells, Cultured, Female, Heart Defects, Congenital, Homocysteine, Humans, Pregnancy, Proteasome Endopeptidase Complex, Rats
Exp. Cell Res.
Date: Dec. 01, 2016
PubMed ID: 28315668
View in: Pubmed Google Scholar
Download Curated Data For This Publication
207416
Switch View:
- Interactions 2
