{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:28:37Z","timestamp":1787855317762,"version":"build-2784847793"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T00:00:00Z","timestamp":1569628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01ES025750"],"award-info":[{"award-number":["R01ES025750"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grace M. 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The goal of this study was to elucidate mechanisms of HAA-induced neurotoxicity through examining a translational biochemical weakness of common PD models. Neuromelanin is a pigmented byproduct of dopamine metabolism that has been debated as being both neurotoxic and neuroprotective in PD. Importantly, neuromelanin is known to bind and potentially release dopaminergic neurotoxicants, including HAAs (eg, \u03b2-carbolines such as harmane). Binding of other HAA subclasses (ie, aminoimidazoaazarenes) to neuromelanin has not been investigated, nor has a specific role for neuromelanin in mediating HAA-induced neurotoxicity been examined. Thus, we investigated the role of neuromelanin in modulating HAA-induced neurotoxicity. We characterized melanin from Sepia officinalis and synthetic dopamine melanin, proposed neuromelanin analogs with similar biophysical properties. Using a cell-free assay, we demonstrated strong binding of harmane and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to neuromelanin analogs. To increase cellular neuromelanin, we transfected SH-SY5Y neuroblastoma cells with tyrosinase. Relative to controls, tyrosinase-expressing cells exhibited increased neuromelanin levels, cellular HAA uptake, cell toxicity, and oxidative damage. Given that typical cellular and rodent PD models form far lower neuromelanin levels than humans, there is a critical translational weakness in assessing HAA-neurotoxicity. The primary impacts of these results are identification of a potential mechanism by which HAAs accumulate in catecholaminergic neurons and support for the need to conduct neurotoxicity studies in systems forming neuromelanin.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz210","type":"journal-article","created":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T07:28:02Z","timestamp":1569482882000},"page":"171-188","source":"Crossref","is-referenced-by-count":35,"title":["Neuromelanin Modulates Heterocyclic Aromatic Amine-Induced Dopaminergic Neurotoxicity"],"prefix":"10.1093","volume":"173","author":[{"given":"Vivek","family":"Lawana","sequence":"first","affiliation":[{"name":"School of Health Sciences"},{"name":"Purdue Institute for Integrative Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Young","family":"Um","sequence":"additional","affiliation":[{"name":"College of Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Rochet","sequence":"additional","affiliation":[{"name":"Purdue Institute for Integrative Neuroscience"},{"name":"Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-9903","authenticated-orcid":false,"given":"Robert J","family":"Turesky","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H","family":"Shannahan","sequence":"additional","affiliation":[{"name":"School of Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R","family":"Cannon","sequence":"additional","affiliation":[{"name":"School of Health Sciences"},{"name":"Purdue Institute for Integrative Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,28]]},"reference":[{"key":"2020010609480409500_kfz210-B1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tiv.2018.05.003","article-title":"Experimental challenges regarding the in vitro investigation of the nanoparticle-biocorona in disease states","volume":"51","author":"Adamson","year":"2018","journal-title":"Toxicol. 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Ultrastructural comparison of neuromelanin with other melanins","volume":"142","author":"Kemali","year":"1985","journal-title":"J. Anat."},{"key":"2020010609480409500_kfz210-B50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1471-4159.2005.03342.x","article-title":"Immobilization stress causes increases in tetrahydrobiopterin, dopamine, and neuromelanin and oxidative damage in the nigrostriatal system","volume":"95","author":"Kim","year":"2005","journal-title":"J. Neurochem"},{"key":"2020010609480409500_kfz210-B51","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0197-0186(90)90122-A","article-title":"3-Amino-1-methyl-5h-pyrido[4,3-B]indole (Trp-P-2) and other heterocyclic amines as inhibitors of mitochondrial monoamine oxidases Separated from human brain synaptosomes","volume":"16","author":"Kojima","year":"1990","journal-title":"Neurochem. 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