Spontaneous Formation of Melanin from Dopamine in the Presence of Iron

David M Hedges; Jordan T Yorgason; Andrew W Perez; Nathan D Schilaty; Benjamin M Williams; Richard K Watt; Scott C Steffensen

doi:10.3390/antiox9121285

Spontaneous Formation of Melanin from Dopamine in the Presence of Iron

Antioxidants (Basel). 2020 Dec 16;9(12):1285. doi: 10.3390/antiox9121285.

Authors

David M Hedges^{1

2}, Jordan T Yorgason^{3

4}, Andrew W Perez⁴, Nathan D Schilaty^{4

5

6

7}, Benjamin M Williams⁴, Richard K Watt², Scott C Steffensen^{4

5}

Affiliations

¹ Enterprise Information Management, Billings Clinic, 2800 10th Avenue North, Billings, MT 59101, USA.
² Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, UT 84602, USA.
³ Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
⁴ Neuroscience Program, S-192 ESC, Brigham Young University, Provo, UT 84602, USA.
⁵ Department of Psychology, 1001 KMBL, Brigham Young University, Provo, UT 84602, USA.
⁶ Departments of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
⁷ Departments of Physiology & Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Abstract

Parkinson's disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, and products of DA conversion to melanin in vitro, and DA melanogenesis under varying levels of Fe³⁺, pro-oxidants, and antioxidants were examined. The rate of melanogenesis for DA was substantially greater than related catecholamines norepinephrine and epinephrine and their precursor amino acids tyrosine and l-Dopa as measured by UV-IR spectrophotometry. Dopamine melanogenesis was concentration dependent on the pro-oxidant species and Fe³⁺. Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC₅₀ = 500 μM) and decreased by the antioxidants ascorbate (IC₅₀ = 10 μM) and glutathione (GSH; IC₅₀ = 5 μM). Spectrophotometric results were corroborated by tuning a fast-scan cyclic voltammetry system to monitor DA melanogenesis. Evoked DA release in striatal brain slices resulted in NM formation that was prevented by GSH. These findings suggest that DA melanogenesis occurs spontaneously under physiologically-relevant conditions of oxidative stress and that NM may act as a marker of past exposure to oxidative stress.

Keywords: dopamine; iron; melanin; neuromelanin; oxidative stress.

Abstract

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