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Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method

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-...

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Autores principales: Bui, Thi Bao Chau, Nosaki, Shohei, Kokawa, Mito, Xu, Yuqun, Kitamura, Yutaka, Tanokura, Masaru, Hachimura, Satoshi, Miyakawa, Takuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493444/
https://www.ncbi.nlm.nih.gov/pubmed/33950219
http://dx.doi.org/10.1042/BSR20210491
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author Bui, Thi Bao Chau
Nosaki, Shohei
Kokawa, Mito
Xu, Yuqun
Kitamura, Yutaka
Tanokura, Masaru
Hachimura, Satoshi
Miyakawa, Takuya
author_facet Bui, Thi Bao Chau
Nosaki, Shohei
Kokawa, Mito
Xu, Yuqun
Kitamura, Yutaka
Tanokura, Masaru
Hachimura, Satoshi
Miyakawa, Takuya
author_sort Bui, Thi Bao Chau
collection PubMed
description 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.
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spelling pubmed-84934442021-10-08 Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method Bui, Thi Bao Chau Nosaki, Shohei Kokawa, Mito Xu, Yuqun Kitamura, Yutaka Tanokura, Masaru Hachimura, Satoshi Miyakawa, Takuya Biosci Rep Biochemical Techniques & Resources 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. Portland Press Ltd. 2021-05-20 /pmc/articles/PMC8493444/ /pubmed/33950219 http://dx.doi.org/10.1042/BSR20210491 Text en © 2021 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biochemical Techniques & Resources
Bui, Thi Bao Chau
Nosaki, Shohei
Kokawa, Mito
Xu, Yuqun
Kitamura, Yutaka
Tanokura, Masaru
Hachimura, Satoshi
Miyakawa, Takuya
Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
title Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
title_full Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
title_fullStr Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
title_full_unstemmed Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
title_short Evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
title_sort evaluation of spice and herb as phyto-derived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method
topic Biochemical Techniques & Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493444/
https://www.ncbi.nlm.nih.gov/pubmed/33950219
http://dx.doi.org/10.1042/BSR20210491
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