Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems

Molecules

Dominika Mániková⁴  Lucia Medvecová Letavayová⁴  Danuᘚ Vlasáková⁴  Pavol Košík³  Ethiene Castellucci Estevam²  Muhammad Jawad Nasim²  Martin Gruhlke¹  Alan Slusarenko¹  Torsten Burkholz²  Claus Jacob² 

[1] Department of Plant Physiology (BioIII), RWTH Aachen University, D-52056 Aachen, Germany; E-Mails:;Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B 2.1, D-66123 Saarbruecken, Germany; E-Mails:;Department of Oncology, Cancer Research Institute, Vlárska 7, 833 91 Bratislava, Slovakia; E-Mail:;Department of Genetics, Cancer Research Institute, Vlárska 7, 833 91 Bratislava, Slovakia; E-Mails:

关键词: chemogenomic screening;    intracellular thiolstat;    intracellular diagnostics;    redox modulation;    nematodes;    Saccharomyces cerevisiae;    thiolstat;   

DOI  :  10.3390/molecules190812258

来源: mdpi

【 摘 要 】

Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-)chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the “redox link” which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.