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IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism
Insulin-degrading enzyme (IDE) was applied to catalyze hydrolysis of Nociceptin/Orphanin 1-16 (OFQ/N) to show the involvement of the enzyme in degradation of neuropeptides engaged in pain transmission. Moreover, IDE degradative action towards insulin (Ins) was inhibited by the OFQ/N fragments, sugge...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770469/ https://www.ncbi.nlm.nih.gov/pubmed/31509943 http://dx.doi.org/10.3390/ijms20184447 |
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author | Zingale, Gabriele Antonio Bellia, Francesco Ahmed, Ikhlas Mohamed Mohamud Mielczarek, Przemyslaw Silberring, Jerzy Grasso, Giuseppe |
author_facet | Zingale, Gabriele Antonio Bellia, Francesco Ahmed, Ikhlas Mohamed Mohamud Mielczarek, Przemyslaw Silberring, Jerzy Grasso, Giuseppe |
author_sort | Zingale, Gabriele Antonio |
collection | PubMed |
description | Insulin-degrading enzyme (IDE) was applied to catalyze hydrolysis of Nociceptin/Orphanin 1-16 (OFQ/N) to show the involvement of the enzyme in degradation of neuropeptides engaged in pain transmission. Moreover, IDE degradative action towards insulin (Ins) was inhibited by the OFQ/N fragments, suggesting a possible regulatory mechanism in the central nervous system. It has been found that OFQ/N and Ins affect each other degradation by IDE, although in a different manner. Indeed, while the digestion of OFQ/N is significantly affected by the presence of Ins, the kinetic profile of the Ins hydrolysis is not affected by the presence of OFQ/N. However, the main hydrolytic fragments of OFQ/N produced by IDE exert inhibitory activity towards the IDE-mediated Ins degradation. Here, we present the results indicating that, besides Ins, IDE cleaves neuropeptides and their released fragments act as inhibitors of IDE activity toward Ins. Having in mind that IDE is present in the brain, which also contains Ins receptors, it cannot be excluded that this enzyme indirectly participates in neural communication of pain signals and that neuropeptides involved in pain transmission may contribute to the regulation of IDE activity. Finally, preliminary results on the metabolism of OFQ/N, carried out in the rat spinal cord homogenate in the presence of various inhibitors specific for different classes of proteases, show that OFQ/N proteolysis in rat spinal cord could be due, besides IDE, also to a cysteine protease not yet identified. |
format | Online Article Text |
id | pubmed-6770469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67704692019-10-30 IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism Zingale, Gabriele Antonio Bellia, Francesco Ahmed, Ikhlas Mohamed Mohamud Mielczarek, Przemyslaw Silberring, Jerzy Grasso, Giuseppe Int J Mol Sci Article Insulin-degrading enzyme (IDE) was applied to catalyze hydrolysis of Nociceptin/Orphanin 1-16 (OFQ/N) to show the involvement of the enzyme in degradation of neuropeptides engaged in pain transmission. Moreover, IDE degradative action towards insulin (Ins) was inhibited by the OFQ/N fragments, suggesting a possible regulatory mechanism in the central nervous system. It has been found that OFQ/N and Ins affect each other degradation by IDE, although in a different manner. Indeed, while the digestion of OFQ/N is significantly affected by the presence of Ins, the kinetic profile of the Ins hydrolysis is not affected by the presence of OFQ/N. However, the main hydrolytic fragments of OFQ/N produced by IDE exert inhibitory activity towards the IDE-mediated Ins degradation. Here, we present the results indicating that, besides Ins, IDE cleaves neuropeptides and their released fragments act as inhibitors of IDE activity toward Ins. Having in mind that IDE is present in the brain, which also contains Ins receptors, it cannot be excluded that this enzyme indirectly participates in neural communication of pain signals and that neuropeptides involved in pain transmission may contribute to the regulation of IDE activity. Finally, preliminary results on the metabolism of OFQ/N, carried out in the rat spinal cord homogenate in the presence of various inhibitors specific for different classes of proteases, show that OFQ/N proteolysis in rat spinal cord could be due, besides IDE, also to a cysteine protease not yet identified. MDPI 2019-09-10 /pmc/articles/PMC6770469/ /pubmed/31509943 http://dx.doi.org/10.3390/ijms20184447 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zingale, Gabriele Antonio Bellia, Francesco Ahmed, Ikhlas Mohamed Mohamud Mielczarek, Przemyslaw Silberring, Jerzy Grasso, Giuseppe IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism |
title | IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism |
title_full | IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism |
title_fullStr | IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism |
title_full_unstemmed | IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism |
title_short | IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism |
title_sort | ide degrades nociceptin/orphanin fq through an insulin regulated mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770469/ https://www.ncbi.nlm.nih.gov/pubmed/31509943 http://dx.doi.org/10.3390/ijms20184447 |
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