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Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation

The degradation of target proteins by small molecules utilizing the cellular proteolytic system is featured as a treatment strategy of several diseases. We found that S-1-propenylcysteine (S1PC) among several cysteine derivatives in aged garlic extract inhibited TLR-mediated IL-6 production by induc...

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Autores principales: Suzuki, Jun-ichiro, Kodera, Yukihiro, Miki, Satomi, Ushijima, Mitsuyasu, Takashima, Miyuki, Matsutomo, Toshiaki, Morihara, Naoaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148218/
https://www.ncbi.nlm.nih.gov/pubmed/30237533
http://dx.doi.org/10.1038/s41598-018-32431-0
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author Suzuki, Jun-ichiro
Kodera, Yukihiro
Miki, Satomi
Ushijima, Mitsuyasu
Takashima, Miyuki
Matsutomo, Toshiaki
Morihara, Naoaki
author_facet Suzuki, Jun-ichiro
Kodera, Yukihiro
Miki, Satomi
Ushijima, Mitsuyasu
Takashima, Miyuki
Matsutomo, Toshiaki
Morihara, Naoaki
author_sort Suzuki, Jun-ichiro
collection PubMed
description The degradation of target proteins by small molecules utilizing the cellular proteolytic system is featured as a treatment strategy of several diseases. We found that S-1-propenylcysteine (S1PC) among several cysteine derivatives in aged garlic extract inhibited TLR-mediated IL-6 production by inducing the degradation of adaptor protein MyD88. We showed that S1PC directly denatured MyD88 and induced the formation of protein aggregates. Consequently, MyD88 was degraded by aggresome-autophagy pathway. On the other hand, S-allylcysteine, a structural analog of S1PC, failed to induce the degradation of MyD88 because of its inability to denature MyD88 although it also activated autophagy. Our findings suggest that S1PC induces MyD88 degradation through the denaturation of MyD88 and the activation of autophagy. Thus, S1PC may serve as the base to develop a therapeutic means for immune diseases associated with aberrant TLR signaling pathways.
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spelling pubmed-61482182019-02-12 Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation Suzuki, Jun-ichiro Kodera, Yukihiro Miki, Satomi Ushijima, Mitsuyasu Takashima, Miyuki Matsutomo, Toshiaki Morihara, Naoaki Sci Rep Article The degradation of target proteins by small molecules utilizing the cellular proteolytic system is featured as a treatment strategy of several diseases. We found that S-1-propenylcysteine (S1PC) among several cysteine derivatives in aged garlic extract inhibited TLR-mediated IL-6 production by inducing the degradation of adaptor protein MyD88. We showed that S1PC directly denatured MyD88 and induced the formation of protein aggregates. Consequently, MyD88 was degraded by aggresome-autophagy pathway. On the other hand, S-allylcysteine, a structural analog of S1PC, failed to induce the degradation of MyD88 because of its inability to denature MyD88 although it also activated autophagy. Our findings suggest that S1PC induces MyD88 degradation through the denaturation of MyD88 and the activation of autophagy. Thus, S1PC may serve as the base to develop a therapeutic means for immune diseases associated with aberrant TLR signaling pathways. Nature Publishing Group UK 2018-09-20 /pmc/articles/PMC6148218/ /pubmed/30237533 http://dx.doi.org/10.1038/s41598-018-32431-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Suzuki, Jun-ichiro
Kodera, Yukihiro
Miki, Satomi
Ushijima, Mitsuyasu
Takashima, Miyuki
Matsutomo, Toshiaki
Morihara, Naoaki
Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation
title Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation
title_full Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation
title_fullStr Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation
title_full_unstemmed Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation
title_short Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing MyD88 degradation
title_sort anti-inflammatory action of cysteine derivative s-1-propenylcysteine by inducing myd88 degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148218/
https://www.ncbi.nlm.nih.gov/pubmed/30237533
http://dx.doi.org/10.1038/s41598-018-32431-0
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