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Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway

Melanin, a pigment synthesized by melanocytes in the skin, resists the damage caused by ultraviolet rays to cells. Citric acid, a well-known food additive, is commonly used as an antioxidant and is an important part of the tricarboxylic acid (TCA) cycle for energy production during cellular metaboli...

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Autores principales: Zhou, Siqi, Sakamoto, Kazuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746170/
https://www.ncbi.nlm.nih.gov/pubmed/33332393
http://dx.doi.org/10.1371/journal.pone.0243565
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author Zhou, Siqi
Sakamoto, Kazuichi
author_facet Zhou, Siqi
Sakamoto, Kazuichi
author_sort Zhou, Siqi
collection PubMed
description Melanin, a pigment synthesized by melanocytes in the skin, resists the damage caused by ultraviolet rays to cells. Citric acid, a well-known food additive, is commonly used as an antioxidant and is an important part of the tricarboxylic acid (TCA) cycle for energy production during cellular metabolism. Here, we aimed to investigate whether the addition of excess citric acid regulates melanin synthesis, and to delineate the underlying mechanism. First, we observed that citric acid exerts opposite redox effects on mouse and human cells. Interestingly, treatment with excess citric acid increased the melanin content in mouse cells but decreased it in human cells. Furthermore, the expression of factors important for melanin synthesis, such as microphthalmia-associated transcription factor (MITF), was also regulated by citric acid treatment—it was promoted in mouse cells and suppressed in human cells. Citric acid also impacted the upstream regulators of MITF, glycogen synthase kinase 3β (GSK3β), and β-catenin. Second, we determined the importance of GSK3β in the citric acid-mediated regulation of melanin synthesis, using a GSK3β inhibitor (BIO). To the best of our knowledge, this is the first study to show that citric acid regulates melanin synthesis via the GSK3β/β-catenin signaling pathway, and that equal amounts of exogenous citric acid exert opposing effects on mouse and human cells.
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spelling pubmed-77461702020-12-31 Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway Zhou, Siqi Sakamoto, Kazuichi PLoS One Research Article Melanin, a pigment synthesized by melanocytes in the skin, resists the damage caused by ultraviolet rays to cells. Citric acid, a well-known food additive, is commonly used as an antioxidant and is an important part of the tricarboxylic acid (TCA) cycle for energy production during cellular metabolism. Here, we aimed to investigate whether the addition of excess citric acid regulates melanin synthesis, and to delineate the underlying mechanism. First, we observed that citric acid exerts opposite redox effects on mouse and human cells. Interestingly, treatment with excess citric acid increased the melanin content in mouse cells but decreased it in human cells. Furthermore, the expression of factors important for melanin synthesis, such as microphthalmia-associated transcription factor (MITF), was also regulated by citric acid treatment—it was promoted in mouse cells and suppressed in human cells. Citric acid also impacted the upstream regulators of MITF, glycogen synthase kinase 3β (GSK3β), and β-catenin. Second, we determined the importance of GSK3β in the citric acid-mediated regulation of melanin synthesis, using a GSK3β inhibitor (BIO). To the best of our knowledge, this is the first study to show that citric acid regulates melanin synthesis via the GSK3β/β-catenin signaling pathway, and that equal amounts of exogenous citric acid exert opposing effects on mouse and human cells. Public Library of Science 2020-12-17 /pmc/articles/PMC7746170/ /pubmed/33332393 http://dx.doi.org/10.1371/journal.pone.0243565 Text en © 2020 Zhou, Sakamoto http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhou, Siqi
Sakamoto, Kazuichi
Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway
title Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway
title_full Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway
title_fullStr Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway
title_full_unstemmed Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway
title_short Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway
title_sort citric acid promoted melanin synthesis in b16f10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and hmv-ii melanoma cells via the gsk3β/β-catenin signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746170/
https://www.ncbi.nlm.nih.gov/pubmed/33332393
http://dx.doi.org/10.1371/journal.pone.0243565
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