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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...

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Autores principales: Zingale, Gabriele Antonio, Bellia, Francesco, Ahmed, Ikhlas Mohamed Mohamud, Mielczarek, Przemyslaw, Silberring, Jerzy, Grasso, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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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.
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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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