Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/34689

Schisandrin B elicits a glutathione antioxidant response and protects against apoptosis via the redox-sensitive ERK/Nrf2 pathway in AML12 hepatocytes

Authors Leong, Pou Kuan HKUST affiliated (currently or previously)
Chiu, Po Yee HKUST affiliated (currently or previously)
Chen, Na HKUST affiliated (currently or previously).
Leung, Hoiyan HKUST affiliated (currently or previously)
Ko, Kam Ming View this author's profile
Issue Date 2011
Source Free radical research , v. 45, (4), 2011, p. 483-495
Summary This study examined the effects of (-)schisandrin B [(-)Sch B] on MAPK and Nrf2 activation and the subsequent induction of glutathione antioxidant response and cytoprotection against apoptosis in AML12 hepatocytes. Pharmacological tools, such as cytochrome P-450 (CYP) inhibitor, antioxidant, MAPK inhibitors and Nrf2 RNAi, were used to delineate the signalling pathway. (-)Sch B caused a time-dependent activation of MAPK in AML12 cells, particularly the ERK1/2. The MAPK activation was followed by an enhancement in Nrf2 nuclear translocation and the eliciting of a glutathione antioxidant response. Reactive oxygen species arising from a CYP-catalysed reaction with (-)Sch B seemed to be causally related to the activation of MAPK and Nrf2. ERK inhibition by U0126 or Nrf2 suppression by Nrf2 RNAi transfection almost completely abrogated the cytoprotection against menadione-induced apoptosis in (-)Sch B-pre-treated cells. (-)Sch B pre-treatment potentiated the menadione-induced ERK activation, whereas both p38 and JNK activations were suppressed. Under the condition of ERK inhibition, Sch B treatment did not protect against carbon tetrachloride- hepatotoxicity in an in vivo mouse model. In conclusion, (-)Sch B triggers a redox-sensitive ERK/Nrf2 signalling, which then elicits a cellular glutathione antioxidant response and protects against oxidant-induced apoptosis in AML12 cells. © 2011 Informa UK, Ltd.
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ISSN 1071-5762
Language English
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