Induction of apoptosis in mouse liver by microcystin-LR - A combined   transcriptomic, proteomic, and simulation strategy

doi:10.1074/mcp.M400185-MCP200

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	Induction of apoptosis in mouse liver by microcystin-LR - A combined transcriptomic, proteomic, and simulation strategy
	Chen, T ; Wang, QS ; Cui, J ; Yang, W ; Shi, Q ; Hua, ZC ; Ji, JG ; Shen, PP
刊名	molecular cellular proteomics
	2005
关键词	BCL-2 FAMILY-MEMBERS INDUCED DNA-DAMAGE BLUE-GREEN-ALGAE OXIDATIVE STRESS IN-VIVO MITOCHONDRIAL PERMEABILITY CYANOBACTERIAL TOXIN IRON HOMEOSTASIS RAT HEPATOCYTES OKADAIC ACID
DOI	10.1074/mcp.M400185-MCP200
英文摘要	Microcystins (MCs) are a family of cyclic heptapeptide hepatotoxins produced by freshwater species of cyanobacteria that have been implicated in the development of liver cancer, necrosis, and even deadly intrahepatic bleeding. MC-LR, the most toxic MC variant, is also the most commonly encountered in a contaminated aquatic system. This study presents the first data in the toxicological research of MCs that combines the use of standard apoptotic assays with transcriptomics, proteomic technologies, and computer simulations. By using histochemistry, DNA fragmentation assays, and flow cytometry analysis, we determined that MC-LR causes rapid, dose-dependent apoptosis in mouse liver when BALB/c mice are treated with MC-LR for 24 h at doses of either 50, 60, or 70 mu g/kg of body weight. We then used gene expression profiling to demonstrate differential expressions (> 2-fold) of 61 apoptosis-related genes in cells treated with MC-LR. Further proteomic analysis identified a total of 383 proteins of which 35 proteins were up-regulated and 30 proteins were down-regulated more than 2.5-fold when compared with controls. Combining computer simulations with the transcriptomic and proteomic data, we found that low doses ( 50 mu g/kg) of MC-LR lead to apoptosis primarily through the BID-BAX-BCL-2 pathway, whereas high doses of MC-LR ( 70 mu g/kg) caused apoptosis via a reactive oxygen species pathway. These results indicated that MC-LR exposure can cause apoptosis in mouse liver and revealed two independent pathways playing a major regulatory role in MC-LR-induced apoptosis, thereby contributing to a better understanding of the hepatotoxicity and the tumor-promoting mechanisms of MCs.; Biochemical Research Methods; SCI(E); 0; ARTICLE; 7; 958-974; 4
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/399259]
专题	生命科学学院
推荐引用方式 GB/T 7714	Chen, T,Wang, QS,Cui, J,et al. Induction of apoptosis in mouse liver by microcystin-LR - A combined transcriptomic, proteomic, and simulation strategy[J]. molecular cellular proteomics,2005.
APA	Chen, T.,Wang, QS.,Cui, J.,Yang, W.,Shi, Q.,...&Shen, PP.(2005).Induction of apoptosis in mouse liver by microcystin-LR - A combined transcriptomic, proteomic, and simulation strategy.molecular cellular proteomics.
MLA	Chen, T,et al."Induction of apoptosis in mouse liver by microcystin-LR - A combined transcriptomic, proteomic, and simulation strategy".molecular cellular proteomics (2005).