Differential Effects of Vitamin D Receptor Agonists on Gene Expression in Neonatal Rat ardiomyocytes
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : J. Ruth Wu-Wong , Yung-Wu Chen , Masaki Nakane , Myles Wolf
- چاپ و سال / کشور: 2011
Description
Purpose Vitamin D receptor (VDR) activation is associated with cardiovascular benefits in chronic kidney disease patients, but whether VDR’s hormone and prehormone exhibit similar effects requires more studies. Methods Neonatal rat cardiomyocytes were treated with VDR agonists (calcitriol and/or paricalcitol) and the prehormone calcidiol in the presence of aldo (1 ىM). The expression of VDR target genes were determined by real-time PCR and Western blotting. The expression and activity of CYP27B1 (the enzyme responsible for converting calcidiol to calcitriol) was measured. Results Treating cells with aldo (1 ىM) for 24 h significantly reduced the VDR mRNA (29%) and protein levels (>90%). Calcitriol and calcidiol induced VDR expression in the presence of aldo with EC50 at 0.3 and 7,952 nM, respectively. Calcitriol, paricalcitol and calcidiol stimulated CYP24A1 (EC50 at 6.4, 4.5 and 992 nM, respectively) and suppressed NPPB expression (IC50 at 1.9, 0.1 and 210 nM, respectively) in the presence of 1 ىM aldo. Neonatal rat cardiomyocytes expressed CYP27B1 and converted calcidiol to calcitriol at a low rate (~10% in 24 h). Conclusions VDR hormone calcitriol and its analog paricalcitol exhibit more potent effects than the prehormone calcidiol in cardiomyocytes.
Cardiovasc Drugs Ther (2011) 25:215–222 Published online: 22 March 2011
