Copper supplementation enhances pigmentation and induces dopamine production in ARPE19.
Non-neuronal dopamine production has not been understood despite dopamine function in non-neuronal tissues. Tyrosinase is a non-neuronal enzyme which converts tyrosine to L-DOPA (l-3,4-dihydroxyphenylalanine) and L-DOPA to l-dopaquinone for further melanin production. Since L-DOPA is a dopamine prec...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0327352 |
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| author | Hironori Uehara Baila Shakaib Sangeetha Ravi Kumar Bonnie Archer Balamurali Ambati |
| author_facet | Hironori Uehara Baila Shakaib Sangeetha Ravi Kumar Bonnie Archer Balamurali Ambati |
| author_sort | Hironori Uehara |
| collection | DOAJ |
| description | Non-neuronal dopamine production has not been understood despite dopamine function in non-neuronal tissues. Tyrosinase is a non-neuronal enzyme which converts tyrosine to L-DOPA (l-3,4-dihydroxyphenylalanine) and L-DOPA to l-dopaquinone for further melanin production. Since L-DOPA is a dopamine precursor in neurons, we hypothesized that tyrosinase-derived L-DOPA could alternatively be converted to dopamine. Therefore, this study investigated whether copper supplementation enhanced pigmentation and induced dopamine production via tyrosinase activation in APRE19 cells. Copper is known as a tyrosinase cofactor. In two separate experiments, we cultured ARPE19 in 1% FBS/DMEM with/without 10 μM copper sulfate for approximately 100 days. After 40-50 days, slight pigmentation with copper treatment was confirmed in the cell pellets, while no pigmentation was observed in the non-copper control. After 90-100 days, the pigmentation in the copper treatment group was obvious, while minimal pigmentation was observed in the non-copper control. Dopamine was not detected at 40-50 days in either group, while it was detected after 90-100 days of culture only in the copper-treated group. Tyrosinase mRNA expression was confirmed in both groups at a similar level, while tyrosinase protein expression was significantly higher in the copper treatment group than in the non-copper control. Thus, we determined that copper supplementation efficiently enhances pigmentation and induces dopamine production in long-term culture ARPE19, likely due to increased tyrosinase protein expression and activity. This is the first report showing the significance of copper in non-neuronal dopamine production of RPE cells, which suggests that tyrosinase may be responsible for non-neuronal dopamine production. |
| format | Article |
| id | doaj-art-962df3c2ed194026b362eeb18d722739 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-962df3c2ed194026b362eeb18d7227392025-08-20T03:50:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032735210.1371/journal.pone.0327352Copper supplementation enhances pigmentation and induces dopamine production in ARPE19.Hironori UeharaBaila ShakaibSangeetha Ravi KumarBonnie ArcherBalamurali AmbatiNon-neuronal dopamine production has not been understood despite dopamine function in non-neuronal tissues. Tyrosinase is a non-neuronal enzyme which converts tyrosine to L-DOPA (l-3,4-dihydroxyphenylalanine) and L-DOPA to l-dopaquinone for further melanin production. Since L-DOPA is a dopamine precursor in neurons, we hypothesized that tyrosinase-derived L-DOPA could alternatively be converted to dopamine. Therefore, this study investigated whether copper supplementation enhanced pigmentation and induced dopamine production via tyrosinase activation in APRE19 cells. Copper is known as a tyrosinase cofactor. In two separate experiments, we cultured ARPE19 in 1% FBS/DMEM with/without 10 μM copper sulfate for approximately 100 days. After 40-50 days, slight pigmentation with copper treatment was confirmed in the cell pellets, while no pigmentation was observed in the non-copper control. After 90-100 days, the pigmentation in the copper treatment group was obvious, while minimal pigmentation was observed in the non-copper control. Dopamine was not detected at 40-50 days in either group, while it was detected after 90-100 days of culture only in the copper-treated group. Tyrosinase mRNA expression was confirmed in both groups at a similar level, while tyrosinase protein expression was significantly higher in the copper treatment group than in the non-copper control. Thus, we determined that copper supplementation efficiently enhances pigmentation and induces dopamine production in long-term culture ARPE19, likely due to increased tyrosinase protein expression and activity. This is the first report showing the significance of copper in non-neuronal dopamine production of RPE cells, which suggests that tyrosinase may be responsible for non-neuronal dopamine production.https://doi.org/10.1371/journal.pone.0327352 |
| spellingShingle | Hironori Uehara Baila Shakaib Sangeetha Ravi Kumar Bonnie Archer Balamurali Ambati Copper supplementation enhances pigmentation and induces dopamine production in ARPE19. PLoS ONE |
| title | Copper supplementation enhances pigmentation and induces dopamine production in ARPE19. |
| title_full | Copper supplementation enhances pigmentation and induces dopamine production in ARPE19. |
| title_fullStr | Copper supplementation enhances pigmentation and induces dopamine production in ARPE19. |
| title_full_unstemmed | Copper supplementation enhances pigmentation and induces dopamine production in ARPE19. |
| title_short | Copper supplementation enhances pigmentation and induces dopamine production in ARPE19. |
| title_sort | copper supplementation enhances pigmentation and induces dopamine production in arpe19 |
| url | https://doi.org/10.1371/journal.pone.0327352 |
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