Effects of dl-praeruptorin A on cultured neonatal rat ventricular cardiomyocytes with hypertrophy induced by endothelin-1.

Abstract

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.

• Authors: X Tu, L Miao, Y Kang, H Xia, J-W Tu, Q Wang, Q Tu, J-M Wang, H Hao
• Journal: Methods and findings in experimental and clinical pharmacology (Methods Find Exp Clin Pharmacol) Vol. 31 Issue 4 Pg. 231-6 (May 2009) ISSN: 0379-0355 [Print] Spain
• PMID: 19557200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Chemical References

• Coumarins
• Drugs, Chinese Herbal
• Endothelin-1
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-jun
• bcl-2-Associated X Protein
• praeruptorin A
• Calcium

Topics

• Animals
• Calcium (antagonists & inhibitors)
• Cardiomegaly (drug therapy, metabolism)
• Cells, Cultured
• Coumarins (pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• Endothelin-1 (toxicity)
• Gene Expression Regulation (drug effects)
• Heart Ventricles (cytology)
• Myocardial Contraction (drug effects)
• Myocytes, Cardiac (drug effects, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (drug effects, genetics)
• Proto-Oncogene Proteins c-jun (drug effects, genetics)
• Rats
• Rats, Sprague-Dawley
• bcl-2-Associated X Protein (drug effects, genetics)