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Article

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

1
Institute for Melanin Chemistry, Fujita Health University, Toyoake 470-1192, Aichi, Japan
2
Department of Medical Technology, School of Health Sciences, Gifu University of Medical Science, Seki 501-3892, Gifu, Japan
3
Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Aichi, Japan
4
Department of Biology, University of Massachusetts Boston, Boston, MA 02125, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Botond Penke
Int. J. Mol. Sci. 2021, 22(21), 11751; https://doi.org/10.3390/ijms222111751
Received: 30 September 2021 / Revised: 25 October 2021 / Accepted: 27 October 2021 / Published: 29 October 2021
(This article belongs to the Special Issue Melanins and Melanogenesis 3.0: From Nature to Applications)
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. View Full-Text
Keywords: 3,4-dihydroxyphenylacetaldehyde (DOPAL); 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL); Parkinson’s disease; tyrosinase; ortho-quinone; quinone methide 3,4-dihydroxyphenylacetaldehyde (DOPAL); 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL); Parkinson’s disease; tyrosinase; ortho-quinone; quinone methide
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MDPI and ACS Style

Ito, S.; Tanaka, H.; Ojika, M.; Wakamatsu, K.; Sugumaran, M. Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity. Int. J. Mol. Sci. 2021, 22, 11751. https://doi.org/10.3390/ijms222111751

AMA Style

Ito S, Tanaka H, Ojika M, Wakamatsu K, Sugumaran M. Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity. International Journal of Molecular Sciences. 2021; 22(21):11751. https://doi.org/10.3390/ijms222111751

Chicago/Turabian Style

Ito, Shosuke, Hitomi Tanaka, Makoto Ojika, Kazumasa Wakamatsu, and Manickam Sugumaran. 2021. "Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity" International Journal of Molecular Sciences 22, no. 21: 11751. https://doi.org/10.3390/ijms222111751

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