Protein Biomarkers for in Vitro Testing of Embryotoxicity
详细信息 查看全文
- 作者：Karlfried Groebe ; Katrin Hayess ; Martina Klemm-Manns ; Gerhard Schwall ; Woijciech Wozny ; Margino Steemans ; Annelieke K. Peters ; Chaturvedala Sastri ; Petra Jaeckel ; Werner Stegmann ; Helmut Zengerling ; R
- 刊名：Journal of Proteome Research
- 出版年：2010
- 出版时间：November 5, 2010
- 年：2010
- 卷：9
- 期：11
- 页码：5727-5738
- 全文大小：385K
- 年卷期：v.9,no.11(November 5, 2010)
- ISSN：1535-3907
文摘
There are new challenges for hazard and risk assessment in the chemical industry with regard to REACH legislation in Europe and related activities in the U.S. and Japan, which require the development of novel in vitro models for the molecular characterization of drug- or chemical-related effects replacing conventional animal testing. In the frame of a European FP6 project on reproductive toxicology (ct.eu" class="extLink">www.reprotect.eu), we prepared protein samples from mouse embryonic stem cells differentiated into contracting cardiomyocytes according to the validated embryonic stem cell test (EST) protocol, which had been exposed to toxic substances selected by an expert committee from different in vivo categories of embryotoxicity. Lysates were used to carry out the following investigations: (i) identify optimal dose range conditions in the EST that are suitable for (ii) performing a differential quantitative proteomic study of underlying molecular pathways, (iii) define classes of substances with similar proteomic response patterns, (iv) relate these classes to the traditional in vivo categories of embryotoxicity with (v) the final goal to identify novel surrogate protein biomarker candidates for embryo toxicity. We found two distinct classes of toxic substances (Dinoseb, Ochratoxin-A, and Nitrofen vs β-aminoproprionitril, Metoclopramide, Doxylamine succinate, and class="smallcaps">d-penicillamine) with clear pathway-related differences in their proteomic patterns. Most notably, different responses to cluster 1 and cluster 2 substances were observed for Heat shock protein β-1, Ras-GTPase-activating protein SH3-domain binding protein, Ran binding protein 5, and Calreticulin, Dihydropyrimidinase-like 2 (Ulip2 protein). On the other hand, Heat shock protein 8 and Fscn1 protein were down-regulated by all compounds from both clusters.