| Danshen-Gegen decoction protects against hypoxia/reoxygenation-induced apoptosis by inhibiting mitochondrial permeability transition via the redox-sensitive ERK/Nrf2 and PKCɛ/mK(ATP) pathways in H9c2 cardiomyocytes. | |
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MedLine Citation:
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PMID: 21899994 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Danshen-Gegen (DG) Decoction, an herbal formulation containing Radix Salviae miltiorrhizae and Radix Puerariae lobatae, has been used for the treatment of coronary artery disease in Chinese medicine. In the present study, the involvement of ERK- and PKCɛ-mediated pathways in the cytoprotection against apoptosis afforded by DG pretreatment was investigated in H9c2 cardiomyocytes. Pretreatment with a methanol extract of aqueous DG decoction protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes. The cytoprotection was associated the enhancement of cellular reduced glutathione and a reduced sensitivity to Ca(2+)-induced mitochondrial permeability transition. DG extract increased the production of cytochrome P-450 (CYP)-dependent reactive oxygen species (ROS) in H9c2 cardiomyocytes, which was accompanied by the concomitant activation of ERK1/2 and PKCɛ. The DG-induced ERK1/2 activation was followed by the translocation of Nrf2 from the cytosol to the mitochondria accompanied by an increase in the expression of glutathione-related antioxidant proteins. In addition, the increased expression of hemeoxygenase-1 was associated with the activation of Akt and BAD, indicative of anti-apoptotic activity. In conclusion, DG treatment activated both ERK/Nrf2 and PKCɛ pathways, presumably by ROS arising from CYP-catalyzed processes, with resultant inhibition of hypoxia/reoxygenation-induced apoptosis immediately after DG treatment or even after an extended time interval following DG treatment. |
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Authors:
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Po Yee Chiu; Hoi Yan Leung; Pou Kuan Leong; Na Chen; Limin Zhou; Zhong Zuo; Philip Y Lam; Kam Ming Ko |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-5 |
Journal Detail:
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Title: Phytomedicine : international journal of phytotherapy and phytopharmacology Volume: - ISSN: 1618-095X ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9438794 Medline TA: Phytomedicine Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier GmbH. All rights reserved. |
Affiliation:
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Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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