Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity

Neurogenerative diseases, such as Parkinson’s disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by mon...

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Autores principales:	Shosuke Ito, Hitomi Tanaka, Makoto Ojika, Kazumasa Wakamatsu, Manickam Sugumaran
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	3,4-dihydroxyphenylacetaldehyde (DOPAL) 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) Parkinson’s disease tyrosinase <i>ortho</i>-quinone quinone methide Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/8a9b51fe520c49f8aa93f5c648023294
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spelling	oai:doaj.org-article:8a9b51fe520c49f8aa93f5c6480232942021-11-11T17:12:20ZOxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity10.3390/ijms2221117511422-00671661-6596https://doaj.org/article/8a9b51fe520c49f8aa93f5c6480232942021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11751https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Neurogenerative diseases, such as Parkinson’s disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by monoamine oxidase. DOPAL is well known to exhibit toxic effects on neuronal cells. Both catecholic and aldehyde groups seem to be associated with the neurotoxicity of DOPAL. However, the exact cause of toxicity caused by this compound remains unknown. Since the reactivity of DOPAL could be attributed to its immediate oxidation product, DOPAL-quinone, we examined the potential reactions of this toxic metabolite. The oxidation of DOPAL by mushroom tyrosinase at pH 5.3 produced conventional DOPAL-quinone, but oxidation at pH 7.4 produced the tautomeric quinone-methide, which gave rise to 3,4-dihydroxyphenylglycolaldehyde and 3,4-dihydroxybenzaldehyde as products through a series of reactions. When the oxidation reaction was performed in the presence of ascorbic acid, two additional products were detected, which were tentatively identified as the cyclized products, 5,6-dihydroxybenzofuran and 3,5,6-trihydroxybenzofuran. Physiological concentrations of Cu(II) ions could also cause the oxidation of DOPAL to DOPAL-quinone. DOPAL-quinone exhibited reactivity towards the cysteine residues of serum albumin. DOPAL-oligomer, the oxidation product of DOPAL, exhibited pro-oxidant activity oxidizing GSH to GSSG and producing hydrogen peroxide. These results indicate that DOPAL-quinone generates several toxic compounds that could augment the neurotoxicity of DOPAL.Shosuke ItoHitomi TanakaMakoto OjikaKazumasa WakamatsuManickam SugumaranMDPI AGarticle3,4-dihydroxyphenylacetaldehyde (DOPAL)3,4-dihydroxyphenylglycolaldehyde (DOPEGAL)Parkinson’s diseasetyrosinase<i>ortho</i>-quinonequinone methideBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11751, p 11751 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	3,4-dihydroxyphenylacetaldehyde (DOPAL) 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) Parkinson’s disease tyrosinase <i>ortho</i>-quinone quinone methide Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	3,4-dihydroxyphenylacetaldehyde (DOPAL) 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) Parkinson’s disease tyrosinase <i>ortho</i>-quinone quinone methide Biology (General) QH301-705.5 Chemistry QD1-999 Shosuke Ito Hitomi Tanaka Makoto Ojika Kazumasa Wakamatsu Manickam Sugumaran Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity
description	Neurogenerative diseases, such as Parkinson’s disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by monoamine oxidase. DOPAL is well known to exhibit toxic effects on neuronal cells. Both catecholic and aldehyde groups seem to be associated with the neurotoxicity of DOPAL. However, the exact cause of toxicity caused by this compound remains unknown. Since the reactivity of DOPAL could be attributed to its immediate oxidation product, DOPAL-quinone, we examined the potential reactions of this toxic metabolite. The oxidation of DOPAL by mushroom tyrosinase at pH 5.3 produced conventional DOPAL-quinone, but oxidation at pH 7.4 produced the tautomeric quinone-methide, which gave rise to 3,4-dihydroxyphenylglycolaldehyde and 3,4-dihydroxybenzaldehyde as products through a series of reactions. When the oxidation reaction was performed in the presence of ascorbic acid, two additional products were detected, which were tentatively identified as the cyclized products, 5,6-dihydroxybenzofuran and 3,5,6-trihydroxybenzofuran. Physiological concentrations of Cu(II) ions could also cause the oxidation of DOPAL to DOPAL-quinone. DOPAL-quinone exhibited reactivity towards the cysteine residues of serum albumin. DOPAL-oligomer, the oxidation product of DOPAL, exhibited pro-oxidant activity oxidizing GSH to GSSG and producing hydrogen peroxide. These results indicate that DOPAL-quinone generates several toxic compounds that could augment the neurotoxicity of DOPAL.
format	article
author	Shosuke Ito Hitomi Tanaka Makoto Ojika Kazumasa Wakamatsu Manickam Sugumaran
author_facet	Shosuke Ito Hitomi Tanaka Makoto Ojika Kazumasa Wakamatsu Manickam Sugumaran
author_sort	Shosuke Ito
title	Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity
title_short	Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity
title_full	Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity
title_fullStr	Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity
title_full_unstemmed	Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity
title_sort	oxidative transformations of 3,4-dihydroxyphenylacetaldehyde generate potential reactive intermediates as causative agents for its neurotoxicity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8a9b51fe520c49f8aa93f5c648023294
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_version_	1718432129796276224

Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity

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