Integrated Proteomics, Biological Functional Assessments, and Metabolomics Reveal Toosendanin-Induced Hepatic Energy Metabolic Disorders
文献类型：期刊论文
| 作者 | Yan, Xiaojing1,2; Zhuo, Yue1; Bian, Xiqing1; Li, Jianmin1; Zhang, Yida1; Ma, Lidong1; Lu, Guanghua3; Guo, Ming-Quan4; Wu, Jian-Lin1; Li, Na1 |
| 刊名 | CHEMICAL RESEARCH IN TOXICOLOGY
 |
| 出版日期 | 2019-04-01 |
| 卷号 | 32期号:4页码:668-680 |
| ISSN号 | 0893-228X |
| DOI | 10.1021/acs.chemrestox.8b00350 |
| 英文摘要 | Toosendanin (TSN), a compound from Melia toosendan, exhibits severe hepatotoxicity, which restricts its clinical application. However, the mechanism is not clear. Our previous research found that covalent modification of TSN for proteins might be a possible reason using human liver microsomes, and the glycolytic enzymes, triosephosphate isomerase 1 (TPIS) and alpha-enolase (ENOA), were responsible for the hepatotoxicity. In this study, we tried to prove these findings in cell and animal models by integration of proteomics, metabolomics, and biological methods. Proteomics analysis in rats showed that TPIS and ENOA were covalently modified by TSN reactive metabolites. The biological functional assessments revealed that the modifications inhibited the activity of TPIS and induced the activity of ENOA, in vitro and in vivo, followed by an increase in the level of cellular methylglyoxal, advanced glycation end products, and reactive oxygen species/superoxide, and the induction of mitochondrial dysfunction, which further inhibited oxidative phosphorylation and stimulated glycolysis. Furthermore, metabolomics demonstrated the decrease in the level of metabolites in the tricarboxylic acid cycle, fatty acid beta-oxidation, and amino acid metabolism; i.e., TSN induced hepatocyte energy metabolism disorder. In conclusion, these data suggest novel mechanistic insights into TSN-induced liver injury on the upstream level and provide valuable proteins and energy metabolic targets for diagnosis and therapy in the clinic. |
| 资助项目 | Macao Science and Technology Development Fund[003/2016/A1] ; National Natural Science Foundation of China[81603296] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000465190200016 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7222]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Wu, Jian-Lin; Li, Na |
| 作者单位 | 1.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Ave Wai Long, Taipa, Macao, Peoples R China 2.Nanjing Univ Chinese Med, Changzhou Affiliated Hosp, 25 Heping North Rd, Changzhou 213003, Peoples R China 3.Chengdu Univ Tradit Med, Sch Ethn Med, Chengdu 611137, Sichuan, Peoples R China 4.Chinese Acad Sci, Sino Africa Joint Res Ctr, Wuhan Bot Garden, Key Lab Plant Germplasm Enhancement & Specialty A, Wuhan 430074, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yan, Xiaojing,Zhuo, Yue,Bian, Xiqing,et al. Integrated Proteomics, Biological Functional Assessments, and Metabolomics Reveal Toosendanin-Induced Hepatic Energy Metabolic Disorders[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2019,32(4):668-680. |
| APA | Yan, Xiaojing.,Zhuo, Yue.,Bian, Xiqing.,Li, Jianmin.,Zhang, Yida.,...&Li, Na.(2019).Integrated Proteomics, Biological Functional Assessments, and Metabolomics Reveal Toosendanin-Induced Hepatic Energy Metabolic Disorders.CHEMICAL RESEARCH IN TOXICOLOGY,32(4),668-680. |
| MLA | Yan, Xiaojing,et al."Integrated Proteomics, Biological Functional Assessments, and Metabolomics Reveal Toosendanin-Induced Hepatic Energy Metabolic Disorders".CHEMICAL RESEARCH IN TOXICOLOGY 32.4(2019):668-680. |
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来源：武汉植物园
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