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HERO ID
1040037
Reference Type
Journal Article
Title
Danshen-Gegen decoction protects against hypoxia/reoxygenation-induced apoptosis by inhibiting mitochondrial permeability transition via the redox-sensitive ERK/Nrf2 and PKCε/mKATP pathways in H9c2 cardiomyocytes
Author(s)
Chiu, PY; Leung, HY; Leong, PK; Chen, N; Zhou, L; Zuo, Z; Lam, PY; Ko, KM
Year
2012
Is Peer Reviewed?
1
Journal
Phytomedicine
ISSN:
0944-7113
EISSN:
1618-095X
Volume
19
Issue
2
Page Numbers
99-110
Language
English
PMID
21899994
DOI
10.1016/j.phymed.2011.07.002
Web of Science Id
WOS:000300332800001
Abstract
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 PKCε-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 PKCε. 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 PKCε 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.
Keywords
Salviae miltiorrhizae; Puerariae lobatae; Extracellular signal-regulated protein kinase (ERK); Protein kinase C-epsilon (PKC epsilon); Mitochondrial permeability transition; Apoptosis; H9c2
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Methanol (Non-Cancer)
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