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Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus

In order to elucidate the chemical structure of black to brown pigments, neuromelanins (NMs), in the substantia nigra (SN) and the locus coeruleus (LC) in the central nervous system of humans and other mammalian species during aging, chemical degradative methods are powerful tools. HPLC analysis aft...

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Autores principales: Wakamatsu, Kazumasa, Tabuchi, Keisuke, Ojika, Makoto, Zucca, Fabio A., Zecca, Luigi, Ito, Shosuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014224/
https://www.ncbi.nlm.nih.gov/pubmed/26156066
http://dx.doi.org/10.1111/jnc.13237
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author Wakamatsu, Kazumasa
Tabuchi, Keisuke
Ojika, Makoto
Zucca, Fabio A.
Zecca, Luigi
Ito, Shosuke
author_facet Wakamatsu, Kazumasa
Tabuchi, Keisuke
Ojika, Makoto
Zucca, Fabio A.
Zecca, Luigi
Ito, Shosuke
author_sort Wakamatsu, Kazumasa
collection PubMed
description In order to elucidate the chemical structure of black to brown pigments, neuromelanins (NMs), in the substantia nigra (SN) and the locus coeruleus (LC) in the central nervous system of humans and other mammalian species during aging, chemical degradative methods are powerful tools. HPLC analysis after hydroiodic acid hydrolysis detected aminohydroxyphenylethylamines, aminohydroxyphenylacetic acids, and aminohydroxyethylbenzenes, which confirmed that SN‐NM and LC‐NM contain melanin derived not only from dopamine and norepinephrine (NE) but also from several other catecholic metabolites, such as 3,4‐dihydroxyphenylalanine, 3,4‐dihydroxyphenylacetic acid, 3,4‐dihydroxymandelic acid, 3,4‐dihydroxyphenylethanol, and 3,4‐dihydroxyphenylethylene glycol, in addition to the corresponding Cys‐derivatives in varying degrees. However, hydroiodic acid hydrolysis showed that LC‐NM produced the same degradation products as were detected in SN‐NM. Thus, we needed to develop a new chemical detection method to validate the existence of NE in LC‐NM. In the present study, we report that HCl hydrolysis of LC‐NM in the presence of thioglycolic acid yields new products arising from substitution of the hydroxyl group by thioglycolic acid at the benzyl position of NE and cysteinyl‐NE. This is the first chemical evidence showing that NE and cysteinyl‐NE are incorporated into LC‐NM. [Image: see text] Using the chemical degradation methods for the determination of catechols in neuromelanin (NM), we have shown that dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), 3,4‐dihydroxyphenylethanol (DOPE), and 3,4‐dihydroxyphenylalanine (DOPA) are mainly responsible for the structure of NM from substantia nigra (SN), while norepinephrine (NE), 3,4‐dihydroxymandelic acid (DOMA), and 3,4‐dihydroxyphenylethylene glycol (DOPEG) are additionally responsible for the structure of NM from locus coeruleus (LC).
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spelling pubmed-50142242016-09-19 Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus Wakamatsu, Kazumasa Tabuchi, Keisuke Ojika, Makoto Zucca, Fabio A. Zecca, Luigi Ito, Shosuke J Neurochem ORIGINAL ARTICLES In order to elucidate the chemical structure of black to brown pigments, neuromelanins (NMs), in the substantia nigra (SN) and the locus coeruleus (LC) in the central nervous system of humans and other mammalian species during aging, chemical degradative methods are powerful tools. HPLC analysis after hydroiodic acid hydrolysis detected aminohydroxyphenylethylamines, aminohydroxyphenylacetic acids, and aminohydroxyethylbenzenes, which confirmed that SN‐NM and LC‐NM contain melanin derived not only from dopamine and norepinephrine (NE) but also from several other catecholic metabolites, such as 3,4‐dihydroxyphenylalanine, 3,4‐dihydroxyphenylacetic acid, 3,4‐dihydroxymandelic acid, 3,4‐dihydroxyphenylethanol, and 3,4‐dihydroxyphenylethylene glycol, in addition to the corresponding Cys‐derivatives in varying degrees. However, hydroiodic acid hydrolysis showed that LC‐NM produced the same degradation products as were detected in SN‐NM. Thus, we needed to develop a new chemical detection method to validate the existence of NE in LC‐NM. In the present study, we report that HCl hydrolysis of LC‐NM in the presence of thioglycolic acid yields new products arising from substitution of the hydroxyl group by thioglycolic acid at the benzyl position of NE and cysteinyl‐NE. This is the first chemical evidence showing that NE and cysteinyl‐NE are incorporated into LC‐NM. [Image: see text] Using the chemical degradation methods for the determination of catechols in neuromelanin (NM), we have shown that dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), 3,4‐dihydroxyphenylethanol (DOPE), and 3,4‐dihydroxyphenylalanine (DOPA) are mainly responsible for the structure of NM from substantia nigra (SN), while norepinephrine (NE), 3,4‐dihydroxymandelic acid (DOMA), and 3,4‐dihydroxyphenylethylene glycol (DOPEG) are additionally responsible for the structure of NM from locus coeruleus (LC). John Wiley and Sons Inc. 2015-09-04 2015-11 /pmc/articles/PMC5014224/ /pubmed/26156066 http://dx.doi.org/10.1111/jnc.13237 Text en © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle ORIGINAL ARTICLES
Wakamatsu, Kazumasa
Tabuchi, Keisuke
Ojika, Makoto
Zucca, Fabio A.
Zecca, Luigi
Ito, Shosuke
Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
title Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
title_full Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
title_fullStr Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
title_full_unstemmed Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
title_short Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
title_sort norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014224/
https://www.ncbi.nlm.nih.gov/pubmed/26156066
http://dx.doi.org/10.1111/jnc.13237
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