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Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA
Simultaneous imaging of l-dihydroxyphenylalanine (l-DOPA), dopamine (DA) and norepinephrine (NE) in the catecholamine metabolic pathway is particularly useful because l-DOPA is a neurophysiologically important metabolic intermediate. In this study, we found that 2,4,6-trimethylpyrillium tetrafluorob...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345479/ https://www.ncbi.nlm.nih.gov/pubmed/35917331 http://dx.doi.org/10.1371/journal.pone.0271697 |
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author | Taira, Shu Ikeda, Akari Sugiura, Yuki Shikano, Hitomi Kobayashi, Shoko Terauchi, Tsutomu Yokoyama, Jun |
author_facet | Taira, Shu Ikeda, Akari Sugiura, Yuki Shikano, Hitomi Kobayashi, Shoko Terauchi, Tsutomu Yokoyama, Jun |
author_sort | Taira, Shu |
collection | PubMed |
description | Simultaneous imaging of l-dihydroxyphenylalanine (l-DOPA), dopamine (DA) and norepinephrine (NE) in the catecholamine metabolic pathway is particularly useful because l-DOPA is a neurophysiologically important metabolic intermediate. In this study, we found that 2,4,6-trimethylpyrillium tetrafluoroborate (TMPy) can selectively and efficiently react with target catecholamine molecules. Specifically, simultaneous visualization of DA and NE as metabolites of l-DOPA with high steric hinderance was achieved by derivatized-imaging mass spectrometry (IMS). Interestingly, l-DOPA showed strong localization in the brainstem, in contrast to the pattern of DA and NE, which co-localized with tyrosine hydroxylase (TH). In addition, to identify whether the detected molecules were endogenous or exogenous l-DOPA, mice were injected with l-DOPA deuterated in three positions (D(3)-l-DOPA), which was identifiable by a mass shift of 3Da. TMPy-labeled l-DOPA, DA and NE were detected at m/z 302.1, 258.1 and 274.1, while their D(3) versions were detected at 305.0, 261.1 and 277.1 in mouse brain, respectively. l-DOPA and D(3)-l-DOPA were localized in the BS. DA and NE, and D(3)-DA and D(3)-NE, all of which are metabolites of L-DOPA and D(3)-l-DOPA, were localized in the striatum (STR) and locus coeruleus (LC). These findings suggest a mechanism in the brainstem that allows l-DOPA to accumulate without being metabolized to monoamines downstream of the metabolic pathway. |
format | Online Article Text |
id | pubmed-9345479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-93454792022-08-03 Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA Taira, Shu Ikeda, Akari Sugiura, Yuki Shikano, Hitomi Kobayashi, Shoko Terauchi, Tsutomu Yokoyama, Jun PLoS One Research Article Simultaneous imaging of l-dihydroxyphenylalanine (l-DOPA), dopamine (DA) and norepinephrine (NE) in the catecholamine metabolic pathway is particularly useful because l-DOPA is a neurophysiologically important metabolic intermediate. In this study, we found that 2,4,6-trimethylpyrillium tetrafluoroborate (TMPy) can selectively and efficiently react with target catecholamine molecules. Specifically, simultaneous visualization of DA and NE as metabolites of l-DOPA with high steric hinderance was achieved by derivatized-imaging mass spectrometry (IMS). Interestingly, l-DOPA showed strong localization in the brainstem, in contrast to the pattern of DA and NE, which co-localized with tyrosine hydroxylase (TH). In addition, to identify whether the detected molecules were endogenous or exogenous l-DOPA, mice were injected with l-DOPA deuterated in three positions (D(3)-l-DOPA), which was identifiable by a mass shift of 3Da. TMPy-labeled l-DOPA, DA and NE were detected at m/z 302.1, 258.1 and 274.1, while their D(3) versions were detected at 305.0, 261.1 and 277.1 in mouse brain, respectively. l-DOPA and D(3)-l-DOPA were localized in the BS. DA and NE, and D(3)-DA and D(3)-NE, all of which are metabolites of L-DOPA and D(3)-l-DOPA, were localized in the striatum (STR) and locus coeruleus (LC). These findings suggest a mechanism in the brainstem that allows l-DOPA to accumulate without being metabolized to monoamines downstream of the metabolic pathway. Public Library of Science 2022-08-02 /pmc/articles/PMC9345479/ /pubmed/35917331 http://dx.doi.org/10.1371/journal.pone.0271697 Text en © 2022 Taira et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Taira, Shu Ikeda, Akari Sugiura, Yuki Shikano, Hitomi Kobayashi, Shoko Terauchi, Tsutomu Yokoyama, Jun Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA |
title | Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA |
title_full | Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA |
title_fullStr | Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA |
title_full_unstemmed | Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA |
title_short | Pyrylium based derivatization imaging mass spectrometer revealed the localization of L-DOPA |
title_sort | pyrylium based derivatization imaging mass spectrometer revealed the localization of l-dopa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345479/ https://www.ncbi.nlm.nih.gov/pubmed/35917331 http://dx.doi.org/10.1371/journal.pone.0271697 |
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