首页> 外文OA文献 >A toxicoproteomic study on cardioprotective effects of pre-administration of docetaxel in a mouse model of adriamycin-induced cardiotoxicity.
【2h】

A toxicoproteomic study on cardioprotective effects of pre-administration of docetaxel in a mouse model of adriamycin-induced cardiotoxicity.

机译:在阿霉素诱导的心脏毒性小鼠模型中预先给予多西紫杉醇的心脏保护作用的毒性蛋白质组学研究。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Studies suggest that pre-administration of docetaxel (DOC) in adriamycin (ADR)-DOC combination anticancer therapy results in stronger antitumor effects and fewer ADR-induced cardiotoxic deaths in mouse model, yet no mechanism explaining this effect has been established. The aim of this study was to identify cellular processes in mouse heart tissue affected by different ADR/DOC dosing protocols using a toxicoproteomic approach. We applied fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) - which consists of fluorogenic derivatization, separation and fluorescence detection by LC, and identification by LC-tandem mass spectrometry - to the proteomic analysis of heart tissue from control, intermittent-dosing (DOC-ADR), and simultaneous-dosing (ADR&DOC) groups. In DOC-ADR group, ADR was administered 12h after DOC injection; in ADR&DOC group, both drugs were administered simultaneously; in control group, saline was administered at the same timing as ADR injection of other groups. Heart samples were isolated from all mice 1 week after the treatment. The highly reproducible and sensitive method (FD-LC-MS/MS) identified nine proteins that were differentially expressed in heart tissue of control and the two treatment groups; seven of these nine proteins participate in cellular energy production pathways, including glycolysis, the tricarboxylic acid cycle, and the mitochondrial electron transport chain. Significantly higher expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was observed in the DOC-ADR group, the group with the fewer cardiotoxic deaths, than in the ADR&DOC group. Therefore, GAPDH may have potential as a drug target for protective intervention and a biomarker for evaluation of the cardioprotective effects in pre-clinical studies.
机译:研究表明,多西他赛(DOC)在阿霉素(DOC)-DOC联合抗癌治疗中的预先给药可在小鼠模型中产生更强的抗肿瘤作用,并减少ADR引起的心脏毒性死亡,但尚未建立解释这种作用的机制。这项研究的目的是使用毒理学方法确定受不同ADR / DOC给药方案影响的小鼠心脏组织中的细胞过程。我们将荧光衍生化-液相色谱-串联质谱(FD-LC-MS / MS)-包括荧光衍生化,LC分离和荧光检测以及LC串联质谱鉴定-用于心脏组织的蛋白质组学分析来自控制,间歇给药(DOC-ADR)和同时给药(ADR&DOC)组。 DOC-ADR组在DOC注射后12h给予ADR。在ADR&DOC组中,两种药物同时给药。在对照组中,与其他组注射ADR的时间相同。处理1周后从所有小鼠中分离出心脏样品。高度可重复且灵敏的方法(FD-LC-MS / MS)鉴定了九种在对照组和两个治疗组的心脏组织中差异表达的蛋白质。这九种蛋白质中的七种参与细胞能量产生途径,包括糖酵解,三羧酸循环和线粒体电子传输链。与ADR&DOC组相比,心脏毒性死亡较少的DOC-ADR组中观察到了3-磷酸甘油醛脱氢酶(GAPDH)的高表达。因此,在临床前研究中,GAPDH可能具有作为保护性干预药物靶点和评估心脏保护作用的生物标志物的潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号