Lysine- and cysteine-based protein adductions derived from toxic metabolites of 8-epidiosbulbin E acetate

Lin Dongju; Wang Kai; Guo Xiucai; Gao Huiyuan; Peng Ying; Zheng Jiang

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Lysine- and cysteine-based protein adductions derived from toxic metabolites of 8-epidiosbulbin E acetate

机译：赖氨酸和基于半胱氨酸的蛋白质蛋白增补衍生的8-Epidiosbulbin E醋酸盐的毒性代谢物

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Furanoid 8-epidiosbulbin E acetate (EEA) is a major constituent of herbal medicine Dioscorea bulbifera L. (DB), a traditional herbal medicine widely used in Asian nations. Our early studies demonstrated that administration of EEA caused acute hepatotoxicity in mice and the observed toxicity required P450-mediated metabolic activation. Protein modification by reactive metabolites of EEA has been suggested to be an important mechanism of EEA-induced hepatotoxicity. The objectives of the present study were to investigate the interaction of the electrophilic reactive metabolites derived from EEA with lysine and cysteine residues of proteins and to define the correlation of protein adductions of EEA and the hepatotoxicity induced by EEA. EEA-derived cis-enedial was found to modify both lysine and cysteine residues of proteins. The observed modifications increased with the increase in doses administered in the animals. The formation of protein adductions derived from the reactive metabolites of EEA were potentiated by buthionine sulfoximine, but were attenuated by ketoconazole. This work facilitated better understanding of the mechanisms of toxic action of EEA. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

机译：呋喃醇8-ePIDIOSbulbin E醋酸盐（EEA）是草药Dioscorea Bulbifera L.（DB）的主要组成部分，其一种广泛应用于亚洲国家的传统草药。我们的早期研究表明，EEA的给药导致小鼠中的急性肝毒性和观察到的毒性所需的毒性P450介导的代谢活化。已经提出了通过EEA的反应性代谢物的蛋白质改性是EEA诱导的肝毒性的重要机制。本研究的目的是研究衍生自EEA与赖氨酸和半胱氨酸残基衍生自赖氨酸和半胱氨酸残基的相互作用，并定义EEA的蛋白质增加和EEA诱导的肝毒性的相关性。发现EEA衍生的顺式enedial改变蛋白质的赖氨酸和半胱氨酸残基。观察到的修饰随着动物施用的剂量增加而增加。由甲磺酰硫醚增强衍生自EEA的反应性代谢物的蛋白质增加的形成，但通过酮康唑衰减。这项工作有助于更好地了解EEA的毒性作用的机制。（c）2016 Elsevier Ireland Ltd.保留所有权利。

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来源
《Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research》 |2016年第null期|共9页
作者
Lin Dongju; Wang Kai; Guo Xiucai; Gao Huiyuan; Peng Ying; Zheng Jiang;
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作者单位

Shenyang Pharmaceut Univ Sch Pharm POB 21 103 Wenhua Rd Shenyang 110016 Liaoning Peoples R;

Shenyang Pharmaceut Univ Sch Pharm POB 21 103 Wenhua Rd Shenyang 110016 Liaoning Peoples R;

Shenyang Pharmaceut Univ Sch Pharm POB 21 103 Wenhua Rd Shenyang 110016 Liaoning Peoples R;

Shenyang Pharmaceut Univ Sch Tradit Chinese Med Shenyang 110016 Liaoning Peoples R China;

Shenyang Pharmaceut Univ Sch Pharm POB 21 103 Wenhua Rd Shenyang 110016 Liaoning Peoples R;

Shenyang Pharmaceut Univ Key Lab Struct Based Drug Design &

Discovery Minist Educ Shenyang;

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原文格式 PDF
正文语种 eng
中图分类毒物学（毒理学）;
关键词
8-Epidiosbulbin E acetate; cis-Enedial; Protein adductions; Hepatotoxicity;

机译：θ-opabinvine醋酸盐？kid-horcholel？预先舒适？hebotoxicitis;

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专利

1. Lysine- and cysteine-based protein adductions derived from toxic metabolites of 8-epidiosbulbin E acetate [J] . Lin Dongju, Wang Kai, Guo Xiucai, Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research . 2016,第Null期

机译：赖氨酸和半胱氨酸为基础的蛋白质加合物，其衍生自乙酸8-表皮球蛋白E的有毒代谢产物
2. Cysteine-Based Protein Adduction by Epoxide-Derived Metabolite(s) of Benzbromarone [J] . Wang Hui, Feng Yukun, Wang Qian, Chemical research in toxicology . 2016,第12期

机译：苯并马洛酮的环氧化物衍生代谢产物基于半胱氨酸的蛋白质加成
3. Mass spectrometric characterization of circulating covalent protein adducts derived from a drug Acyl glucuronide metabolite: Multiple albumin adductions in diclofenac patients [J] . HammondT.G., MengX., JenkinsR.E., The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics . 2014,第2期

机译：源自药物酰基葡糖醛酸代谢物的循环共价蛋白加合物的质谱表征：双氯芬酸患者的多个白蛋白加合物
4. Metabolism and protein adduction of a cyclooxygenase-2/15-prostaglandin dehydrogenase derived product from arachidonic acid. [C] . Nathaniel W. Snyder, Alejandro A. Pacheco, Xiaojing Liu, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2013

机译：来自植物酸的环氧氧酶-2 / 15-前列腺素脱氢酶衍生产物的代谢和蛋白质。
5. Analysis of protein adduction kinetics and the effects of protein adduction on c -Jun N -terminal kinase signaling. [D] . Orton, Christopher Reed. 2006

机译：蛋白质内含动力学和蛋白质内含对c -Jun N-末端激酶信号转导的影响分析。
6. Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients [O] . Thomas G. Hammond, Xiaoli Meng, Rosalind E. Jenkins, -1

机译：从药物酰基葡萄糖醛酸化物代谢产物衍生的循环共价蛋白加合物的质谱表征：双氯芬酸患者的多个白蛋白加成
7. Cysteine-Based Protein Adduction by Epoxide-Derived Metabolite(s) of Benzbromarone [O] . -1

机译：基于半胱氨酸的蛋白质通过环氧化物衍生的苯齐突衍生的代谢物

Lysine- and cysteine-based protein adductions derived from toxic metabolites of 8-epidiosbulbin E acetate

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