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Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3
Zinc-α2-glycoprotein (ZAG) is a major plasma protein whose levels increase in chronic energy-demanding diseases and thus serves as an important clinical biomarker in the diagnosis and prognosis of the development of cachexia. Current knowledge suggests that ZAG mediates progressive weight loss throu...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Royal Society
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685929/ https://www.ncbi.nlm.nih.gov/pubmed/32315567 http://dx.doi.org/10.1098/rsob.190035 |
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author | Romauch, Matthias |
author_facet | Romauch, Matthias |
author_sort | Romauch, Matthias |
collection | PubMed |
description | Zinc-α2-glycoprotein (ZAG) is a major plasma protein whose levels increase in chronic energy-demanding diseases and thus serves as an important clinical biomarker in the diagnosis and prognosis of the development of cachexia. Current knowledge suggests that ZAG mediates progressive weight loss through β-adrenergic signalling in adipocytes, resulting in the activation of lipolysis and fat mobilization. Here, through cross-linking experiments, amine oxidase copper-containing 3 (AOC3) is identified as a novel ZAG binding partner. AOC3—also known as vascular adhesion protein 1 (VAP-1) and semicarbazide sensitive amine oxidase (SSAO)—deaminates primary amines, thereby generating the corresponding aldehyde, H(2)O(2) and NH(3). It is an ectoenzyme largely expressed by adipocytes and induced in endothelial cells during inflammation. Extravasation of immune cells depends on amine oxidase activity and AOC3-derived H(2)O(2) has an insulinogenic effect. The observations described here suggest that ZAG acts as an allosteric inhibitor of AOC3 and interferes with the associated pro-inflammatory and anti-lipolytic functions. Thus, inhibition of the deamination of lipolytic hormone octopamine by AOC3 represents a novel mechanism by which ZAG might stimulate lipolysis. Furthermore, experiments involving overexpression of recombinant ZAG reveal that its glycosylation is co-regulated by oxygen availability and that the pattern of glycosylation affects its inhibitory potential. The newly identified protein interaction between AOC3 and ZAG highlights a previously unknown functional relationship, which may be relevant to inflammation, energy metabolism and the development of cachexia. |
format | Online Article Text |
id | pubmed-6685929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-66859292019-08-09 Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 Romauch, Matthias Open Biol Research Zinc-α2-glycoprotein (ZAG) is a major plasma protein whose levels increase in chronic energy-demanding diseases and thus serves as an important clinical biomarker in the diagnosis and prognosis of the development of cachexia. Current knowledge suggests that ZAG mediates progressive weight loss through β-adrenergic signalling in adipocytes, resulting in the activation of lipolysis and fat mobilization. Here, through cross-linking experiments, amine oxidase copper-containing 3 (AOC3) is identified as a novel ZAG binding partner. AOC3—also known as vascular adhesion protein 1 (VAP-1) and semicarbazide sensitive amine oxidase (SSAO)—deaminates primary amines, thereby generating the corresponding aldehyde, H(2)O(2) and NH(3). It is an ectoenzyme largely expressed by adipocytes and induced in endothelial cells during inflammation. Extravasation of immune cells depends on amine oxidase activity and AOC3-derived H(2)O(2) has an insulinogenic effect. The observations described here suggest that ZAG acts as an allosteric inhibitor of AOC3 and interferes with the associated pro-inflammatory and anti-lipolytic functions. Thus, inhibition of the deamination of lipolytic hormone octopamine by AOC3 represents a novel mechanism by which ZAG might stimulate lipolysis. Furthermore, experiments involving overexpression of recombinant ZAG reveal that its glycosylation is co-regulated by oxygen availability and that the pattern of glycosylation affects its inhibitory potential. The newly identified protein interaction between AOC3 and ZAG highlights a previously unknown functional relationship, which may be relevant to inflammation, energy metabolism and the development of cachexia. The Royal Society 2020-04-22 /pmc/articles/PMC6685929/ /pubmed/32315567 http://dx.doi.org/10.1098/rsob.190035 Text en © 2020 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Research Romauch, Matthias Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
title | Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
title_full | Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
title_fullStr | Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
title_full_unstemmed | Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
title_short | Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
title_sort | zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685929/ https://www.ncbi.nlm.nih.gov/pubmed/32315567 http://dx.doi.org/10.1098/rsob.190035 |
work_keys_str_mv | AT romauchmatthias zinca2glycoproteinasaninhibitorofamineoxidasecoppercontaining3 |