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Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin

文献类型：期刊论文

作者Zhang, Yunhai1,2; Qi, Xinming1,2; Gong, Likun1,2; Li, Yan1,2; Liu, Linlin1,2; Xue, Xiang1,2; Xiao, Ying1,2; Wu, Xiongfei1,2; Ren, Jin1
刊名TOXICOLOGY
出版日期2008-07-10
卷号249期号:1页码:62-68
关键词toosendanin primary rat hepatocytes reactive oxygen species (ROS) MAP kinases
ISSN号0300-483X
DOI10.1016/j.tox.2008.04.005
文献子类Article
英文摘要Toosendanin (Tsn), a triterpenoid extracted from Melia toosendan Sieb et Zucc, possesses different pharmacological effects in human and important values in agriculture. However, liver injury has been reported when toosendanin or Melia-family plants, which contain toosendanin are applied. The mechanism by which toosendanin induces liver injury remains largely unknown. Here we reported that toosendanin induced primary rat hepatocytes death by mitochondrial dysfunction and caspase activation. Toosendanin led to decrease of mitochondrial membrane potential, fall in intracellular ATP level, release of cytochrome c to cytoplasm, activation of caspase-8, 9, and 3 and ultimately cell death. Level of reactive oxygen species (ROS) was also increased in hepatocytes after incubation with toosendanin. Catalase, the H2O2-decomposing enzyme, can prevent the reduction in ATP level and protect hepatocytes from toosendanin-induced death. The ERK1/2 (p44/42 MAP kinases) and JNK (c-Jun N-terminal kinase) were activated, but p38 MAPK was not activated by toosendanin. Inhibition of ERK1/2 activation sensitized hepatocytes to death and increased activity of caspase-9 and 3 in response to toosendanin. Inhibition of JNK attenuated toosendanin-induced cell death. These results suggested that toosendanin causes death of primary rat hepatocytes by mitochondrial dysfunction and caspase activation. Generation of ROS and MAP kinases activation might be involved in this process. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
WOS关键词CHINESE TRADITIONAL MEDICINE ; OXIDATIVE STRESS ; CYTOCHROME-C ; CELL INJURY ; APOPTOSIS ; INHIBITION ; ACTIVATION ; INVOLVEMENT ; CASPASES
WOS研究方向Pharmacology & Pharmacy ; Toxicology
语种英语
WOS记录号WOS:000257606800009
出版者ELSEVIER IRELAND LTD
源URL[http://119.78.100.183/handle/2S10ELR8/272866]  
专题药物安全性评价中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Ren, Jin
作者单位1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Yunhai,Qi, Xinming,Gong, Likun,et al. Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin[J]. TOXICOLOGY,2008,249(1):62-68.
APA Zhang, Yunhai.,Qi, Xinming.,Gong, Likun.,Li, Yan.,Liu, Linlin.,...&Ren, Jin.(2008).Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin.TOXICOLOGY,249(1),62-68.
MLA Zhang, Yunhai,et al."Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin".TOXICOLOGY 249.1(2008):62-68.

入库方式： OAI收割

来源：上海药物研究所

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