Spontaneous Formation of Melanin from Dopamine in the Presence of Iron.

Autor: Hedges DM; Enterprise Information Management, Billings Clinic, 2800 10th Avenue North, Billings, MT 59101, USA.; Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, UT 84602, USA., Yorgason JT; Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.; Neuroscience Program, S-192 ESC, Brigham Young University, Provo, UT 84602, USA., Perez AW; Neuroscience Program, S-192 ESC, Brigham Young University, Provo, UT 84602, USA., Schilaty ND; Neuroscience Program, S-192 ESC, Brigham Young University, Provo, UT 84602, USA.; Department of Psychology, 1001 KMBL, Brigham Young University, Provo, UT 84602, USA.; Departments of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.; Departments of Physiology & Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA., Williams BM; Neuroscience Program, S-192 ESC, Brigham Young University, Provo, UT 84602, USA., Watt RK; Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, UT 84602, USA., Steffensen SC; Neuroscience Program, S-192 ESC, Brigham Young University, Provo, UT 84602, USA.; Department of Psychology, 1001 KMBL, Brigham Young University, Provo, UT 84602, USA.
Jazyk: angličtina
Zdroj: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2020 Dec 16; Vol. 9 (12). Date of Electronic Publication: 2020 Dec 16.
DOI: 10.3390/antiox9121285
Abstrakt: 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 Fe 3+ , 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 Fe 3+ . Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC 50 = 500 μM) and decreased by the antioxidants ascorbate (IC 50 = 10 μM) and glutathione (GSH; IC 50 = 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.
Databáze: MEDLINE
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