Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
| Autor: | Yuqun Xu, Satoshi Hachimura, Thi Bao Chau Bui, Shohei Nosaki, Takuya Miyakawa, Yutaka Kitamura, Masaru Tanokura, Mito Kokawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Protein preparation
Biophysics Retinoic acid Aldehyde dehydrogenase Acetaldehyde Protein Engineering Biochemistry chemistry.chemical_compound Biochemical Techniques & Resources Chemical Biology Retinal Humans Spices Molecular Biology Magnesium ion Selective modulator Research Articles ALDH2 Cancer chemistry.chemical_classification biology Aldehyde Dehydrogenase Mitochondrial Retinal Dehydrogenase Cell Biology Aldehyde Dehydrogenase Retinaldehyde dehydrogenase Fluorescence activity assay Enzyme chemistry Retinaldehyde biology.protein Enzymology Signal transduction |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | Selective modulation of retinaldehyde dehydrogenases (RALDHs)—the main aldehyde dehydrogenase (ALDH) enzymes converting retinal into retinoic acid (RA), is very important not only in the RA signaling pathway but also for the potential regulatory effects on RALDH isozyme-specific processes and RALDH-related cancers. However, very few selective modulators for RALDHs have been identified, partly due to variable overexpression protocols of RALDHs and insensitive activity assay that needs to be addressed. In the present study, deletion of the N-terminal disordered regions is found to enable simple preparation of all RALDHs and their closest paralog ALDH2 using a single protocol. Fluorescence-based activity assay was employed for enzymatic activity investigation and screening for RALDH-specific modulators from extracts of various spices and herbs that are well-known for containing many phyto-derived anti-cancer constituents. Under the established conditions, spice and herb extracts exhibited differential regulatory effects on RALDHs/ALDH2 with several extracts showing potential selective inhibition of the activity of RALDHs. In addition, the presence of magnesium ions was shown to significantly increase the activity for the natural substrate retinal of RALDH3 but not the others, while His-tag cleavage considerably increased the activity of ALDH2 for the non-specific substrate retinal. Altogether we propose a readily reproducible workflow to find selective modulators for RALDHs and suggest potential sources of selective modulators from spices and herbs. |
| Databáze: | OpenAIRE |
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