Activation of β-adrenoceptors by dobutamine may induce a higher expression of peroxisome proliferator-activated receptors δ (PPARδ) in neonatal rat cardiomyocytes.
Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors δ (PPARδ) in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARδ in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARδ expression levels and cardiac troponin I (cTnI) phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARδ expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of β1-adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARδ using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARδ is increased by dobutamine in cardiac cells.
Department of Cardiology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan 73101, Taiwan.
Ming-Ting
MT
Chou
Shih-Hsiang
SH
Lo
Kai-Chun
KC
Cheng
Yin-Xiao
YX
Li
Li-Jen
LJ
Chen
Juei-Tang
JT
Cheng
D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D047494:PPAR delta / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D058665:Adrenergic beta-1 Receptor Agonists; D047494:PPAR delta; D004280:Dobutamine; D002118:Calcium