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- Title
Cytochrome P-450-catalyzed reactive oxygen species production mediates the (-)schisandrin B-induced glutathione and heat shock responses in H9c2 cardiomyocytes.
- Authors
Na Chen; Po Yee Chiu; Hoi Yan Leung; Kam Ming Ko
- Abstract
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.
- Publication
Indian Journal of Pharmacology, 2012, Vol 44, Issue 2, p204
- ISSN
0253-7613
- Publication type
Academic Journal
- DOI
10.4103/0253-7613.93849