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Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae.
Biomolecules 2019; 9(10)B

Abstract

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.

Authors+Show Affiliations

Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea. hasikarunarathne@gmail.com.Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea. neelakagm2012@gmail.com.Department of Biology, Jeju National University, Jeju 63243, Korea. myungskim@jejunu.ac.kr.Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 47227, Korea. choiyh@deu.ac.kr.Department of Molecular Biology, Ariel University, Science Park, Ariel 40700, Israel. matanok@gmail.com.Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Korea. epark@knu.ac.kr.Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea. immunkim@jejunu.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31614510

Citation

Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga, et al. "Flumequine-Mediated Upregulation of P38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae." Biomolecules, vol. 9, no. 10, 2019.
Karunarathne WAHM, Molagoda IMN, Kim MS, et al. Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae. Biomolecules. 2019;9(10).
Karunarathne, W. A. H. M., Molagoda, I. M. N., Kim, M. S., Choi, Y. H., Oren, M., Park, E. K., & Kim, G. Y. (2019). Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae. Biomolecules, 9(10), doi:10.3390/biom9100596.
Karunarathne WAHM, et al. Flumequine-Mediated Upregulation of P38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae. Biomolecules. 2019 Oct 11;9(10) PubMed PMID: 31614510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae. AU - Karunarathne,Wisurumuni Arachchilage Hasitha Maduranga, AU - Molagoda,Ilandarage Menu Neelaka, AU - Kim,Myung Sook, AU - Choi,Yung Hyun, AU - Oren,Matan, AU - Park,Eui Kyun, AU - Kim,Gi-Young, Y1 - 2019/10/11/ PY - 2019/08/22/received PY - 2019/09/20/revised PY - 2019/10/10/accepted PY - 2019/10/17/entrez KW - flumequine KW - melanogenesis KW - mitogen-activated protein kinase JF - Biomolecules JO - Biomolecules VL - 9 IS - 10 N2 - 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. SN - 2218-273X UR - https://www.unboundmedicine.com/medline/citation/31614510/Flumequine-Mediated_Upregulation_of_p38_MAPK_and_JNK_Results_in_Melanogenesis_in_B16F10_Cells_and_Zebrafish_Larvae L2 - http://www.mdpi.com/resolver?pii=biom9100596 DB - PRIME DP - Unbound Medicine ER -