Effects of dl-praeruptorin A on cultured neonatal rat ventricular cardiomyocytes with hypertrophy induced by endothelin-1.
The present study investigated whether dl-praeruptorin (Pd-Ia) prevents endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and the potential pathways that underlie such an effect. We assessed cardiomyocyte surface area, protein synthesis, the expression of Bax/Bcl2 and Jun genes, the expression of atrial natriuretic factor (ANF) and Ca2+/calmodulin-dependent kinase II (CaMK-II) activity in cultured neonatal rat ventricular cardiomyocytes with ET-1-induced hypertrophy. It was found that Pd-Ia decreased the surface area and protein synthesis rate in cardiomyocytes exposed to ET-1. Additionally, the expression of Bcl2 and Bax was increased in both the ET-1-exposed and Pd-Ia+ET- 1-treated groups compared with the control group, although this was not significant. In cardiomyocytes incubated with ET-1, the expression of ANF (Nppa) significantly increased relative to the control and Pd-Ia groups. The expression of Jun significantly increased in cardiomyocytes incubated with ET-1, but not in the Pd-Ia group, where Jun levels were similar to those found for the control group. Moreover, it was found that Pd-Ia inhibited the ET-1-induced increase in intracellular Ca(2+) concentration. The results showed that Pd-Ia could conceivably be an effective therapeutic drug for treating the contractile defects associated with cardiac hypertrophy and failure. This activity may be associated with its Ca2+-antagonist effect and modulation of the expression of immediate-early genes that play important roles in the mitogen-activated protein (MAP) kinase pathway.
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Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology & Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, P.R. China. whhuanghao10@yahoo.com.cn
Miao
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Kang
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Xia
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Tu
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Wang
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Tu
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Wang
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Hao
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D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D019332:Endothelin-1 / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
D003374:Coumarins; D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D051028:bcl-2-Associated X Protein; C441070:praeruptorin A; D002118:Calcium