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Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae

Flumequine is a well-known second generation quinolone antibiotic that induces phototoxicity. However, the effect of flumequine on skin melanogenesis is unclear. Therefore, we, for the first time, investigated whether flumequine regulates melanogenesis. The present study showed that flumequine sligh...

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Autores principales: Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga, Molagoda, Ilandarage Menu Neelaka, Kim, Myung Sook, Choi, Yung Hyun, Oren, Matan, Park, Eui Kyun, Kim, Gi-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843389/
https://www.ncbi.nlm.nih.gov/pubmed/31614510
http://dx.doi.org/10.3390/biom9100596
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author Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga
Molagoda, Ilandarage Menu Neelaka
Kim, Myung Sook
Choi, Yung Hyun
Oren, Matan
Park, Eui Kyun
Kim, Gi-Young
author_facet Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga
Molagoda, Ilandarage Menu Neelaka
Kim, Myung Sook
Choi, Yung Hyun
Oren, Matan
Park, Eui Kyun
Kim, Gi-Young
author_sort Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga
collection PubMed
description Flumequine is a well-known second generation quinolone antibiotic that induces phototoxicity. However, the effect of flumequine on skin melanogenesis is unclear. Therefore, we, for the first time, investigated whether flumequine regulates melanogenesis. The present study showed that flumequine slightly inhibited in vitro mushroom tyrosinase activity but significantly increased extracellular and intracellular melanin content in B16F10 cells and promoted the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Additionally, flumequine remarkably increased melanin pigmentation in zebrafish larvae without any toxicity. We also found that flumequine stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation; inhibition of p38 MAPK and JNK resulted in significant downregulation of extracellular and intracellular melanin content in B16F10 cells and pigmentation of zebrafish larvae accompanied with suppression of MITF and tyrosinase expression, indicating that flumequine-mediated p38 and JNK promote melanogenesis in vitro and in vivo. According to the molecular docking prediction, flumequine targeted dual-specificity MAPK phosphatase 16 (DUSP16), which is a major negative regulator of p38 MAPK and JNK. Our findings demonstrate that flumequine induces an increase in melanin content in B16F10 cells and zebrafish larvae by activating p38 MAPK and JNK. These data show the potential of flumequine for use as an anti-vitiligo agent.
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spelling pubmed-68433892019-11-25 Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga Molagoda, Ilandarage Menu Neelaka Kim, Myung Sook Choi, Yung Hyun Oren, Matan Park, Eui Kyun Kim, Gi-Young Biomolecules Article Flumequine is a well-known second generation quinolone antibiotic that induces phototoxicity. However, the effect of flumequine on skin melanogenesis is unclear. Therefore, we, for the first time, investigated whether flumequine regulates melanogenesis. The present study showed that flumequine slightly inhibited in vitro mushroom tyrosinase activity but significantly increased extracellular and intracellular melanin content in B16F10 cells and promoted the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Additionally, flumequine remarkably increased melanin pigmentation in zebrafish larvae without any toxicity. We also found that flumequine stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation; inhibition of p38 MAPK and JNK resulted in significant downregulation of extracellular and intracellular melanin content in B16F10 cells and pigmentation of zebrafish larvae accompanied with suppression of MITF and tyrosinase expression, indicating that flumequine-mediated p38 and JNK promote melanogenesis in vitro and in vivo. According to the molecular docking prediction, flumequine targeted dual-specificity MAPK phosphatase 16 (DUSP16), which is a major negative regulator of p38 MAPK and JNK. Our findings demonstrate that flumequine induces an increase in melanin content in B16F10 cells and zebrafish larvae by activating p38 MAPK and JNK. These data show the potential of flumequine for use as an anti-vitiligo agent. MDPI 2019-10-11 /pmc/articles/PMC6843389/ /pubmed/31614510 http://dx.doi.org/10.3390/biom9100596 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga
Molagoda, Ilandarage Menu Neelaka
Kim, Myung Sook
Choi, Yung Hyun
Oren, Matan
Park, Eui Kyun
Kim, Gi-Young
Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae
title Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae
title_full Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae
title_fullStr Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae
title_full_unstemmed Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae
title_short Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae
title_sort flumequine-mediated upregulation of p38 mapk and jnk results in melanogenesis in b16f10 cells and zebrafish larvae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843389/
https://www.ncbi.nlm.nih.gov/pubmed/31614510
http://dx.doi.org/10.3390/biom9100596
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