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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...

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Autores principales: Taira, Shu, Ikeda, Akari, Sugiura, Yuki, Shikano, Hitomi, Kobayashi, Shoko, Terauchi, Tsutomu, Yokoyama, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
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.
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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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