| Cytochrome P-450-catalyzed reactive oxygen species production mediates the (-)Schisandrin B-induced glutathione and heat shock responses in AML12 hepatocytes. | |
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MedLine Citation:
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PMID: 22070356 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Schisandrin B (Sch B), the most abundant dibenzocyclooctadiene lignan in Fructus Schisandrae, has been shown to induce glutathione antioxidant and heat shock responses, as well as protect against oxidant-induced injury in various tissues, including that of the liver, in rodents and in AML12 hepatocytes. (-)Sch B was found to be the most potent stereoisomer of Sch B in producing cytoprotective action in AML12 hepatocytes. To define the role of reactive oxygen species (ROS) arising from cytochrome P-450 (CYP)-catalyzed metabolism of (-)Sch B in triggering glutathione antioxidant and heat shock responses, the effects of CYP inhibitor (aminobenzotriazole, ABT) and antioxidants (dimethylthiouracil, DTMU, and Trolox, TRX) on (-)Sch B-induced ROS production and associated increases in cellular reduced glutathione (GSH) level as well as heat shock protein (Hsp) 25/70 production were investigated in AML12 hepatocytes. The results indicated that (-)Sch B caused a dose-dependent and sustained increase in ROS production over an incubation period of 6 h in AML12 hepatocytes, which was completely suppressed by pre-/co-treatment with ABT or DTMU/TRX. The incubation with (-)Sch B for 6 h caused optimal and dose-dependent increases in cellular GSH level and Hsp 25/70 production at 16 h post-drug exposure in AML12 hepatocytes. These cellular responses were associated with protection against menadione-induced apoptosis. Pre-/co-treatment with ABT or antioxidants completely abrogated the (-)Sch B-induced glutathione antioxidant and heat shock responses, as well as protection against menadione-induced apoptosis. Experimental evidence obtained so far supports the causal role of ROS arising from the CYP-catalyzed metabolism of (-)Sch B in eliciting glutathione antioxidant and heat shock responses in AML12 hepatocytes. Keywords: Schisandrin B; Cytochrome P-450; Reactive oxygen species; Glutathione; Heat shock protein; Apoptosis; AML12. |
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Authors:
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Pou Kuan Leong; Po Yee Chiu; Hoi Yan Leung; Kam Ming Ko |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-10 |
Journal Detail:
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Title: Cell biology international Volume: - ISSN: 1095-8355 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9307129 Medline TA: Cell Biol Int Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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