| RESEARCH ARTICLE |
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| Year : 2012 | Volume
: 44
| Issue : 2 | Page : 204-209 |
Cytochrome P-450-catalyzed reactive oxygen species production mediates the (-)schisandrin B-induced glutathione and heat shock responses in H9c2 cardiomyocytes
Na Chen, Po Yee Chiu, Hoi Yan Leung, Kam Ming Ko
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China
Correspondence Address:
Kam Ming Ko
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.93849
Objective: Schisandrin B (Sch B) is the most abundant, active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis (Turcz) Baillon (Schisandraceae). (-)Sch B was found to be the most potent stereoisomer of Sch B in producing cytoprotective action in H9c2 cardiomyocytes. The elucidation of biochemical mechanism underlying the cytoprotection of (-)Sch B has attracted much interest in the area of preventive medicine. Here, we examined whether the (-)Sch B-induced enhancement of glutathione antioxidant and heat shock responses and the associated cytoprotection against hypoxia/reoxygenation-induced apoptosis are mediated by reactive oxygen species (ROS) arising from cytochrome P-450 (CYP)-catalyzed metabolism of (-)Sch B in H9c2 cardiomyocytes.
Materials and Methods: The effects of CYP inhibitor (1-aminobenzotriazole, ABT) and antioxidant (dimethylthiouracil, DMTU) 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 H9c2 cardiomyocytes. The (-)Sch B-induced ROS generation was monitored with or without ABT/DMTU for 6 h in situ, while (-)Sch B-induced cellular GSH level and Hsp 25/70 production, as well as cytoprotection were measured at 16 h post-(-)Sch B exposure.
Results: The results indicated that (-)Sch B caused a dose-dependent increase in ROS production in H9c2 cardiomyocytes, which was completely suppressed by pre- and co-treatment with ABT or DTMU. The incubation with (-)Sch B for 6 h caused dose-dependent increases in cellular GSH level and Hsp 25/70 production, as well as protection against hypoxia/reoxygenation-induced apoptosis at 16-h post-drug exposure in H9c2 cardiomyocytes. All these cellular responses were abrogated by treatment with ABT or DMTU.
Conclusion: The results suggest that ROS arising from the CYP-catalyzed metabolism of (-)Sch B elicit glutathione antioxidant and heat shock responses, thereby protecting against oxidant-induced apoptosis in H9c2 cardiomyocytes.
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