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Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide
Paired box gene 3 (Pax3) and cAMP responsive element-binding protein (CREB) directly interact with the cis-acting elements on the promoter of microphthalmia-associated transcription factor isoform M (MITF-M) for transcriptional activation in the melanogenic process. Tyrosinase (Tyro) is a target gen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766340/ https://www.ncbi.nlm.nih.gov/pubmed/33348800 http://dx.doi.org/10.3390/ijms21249631 |
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author | Choi, Yong-Pyo Kim, Ga Hyun Kim, Song-Hee Maeng, Jongseo Lee, Heesoon Han, Sang-Bae Kim, Ki Ho Kim, Youngsoo |
author_facet | Choi, Yong-Pyo Kim, Ga Hyun Kim, Song-Hee Maeng, Jongseo Lee, Heesoon Han, Sang-Bae Kim, Ki Ho Kim, Youngsoo |
author_sort | Choi, Yong-Pyo |
collection | PubMed |
description | Paired box gene 3 (Pax3) and cAMP responsive element-binding protein (CREB) directly interact with the cis-acting elements on the promoter of microphthalmia-associated transcription factor isoform M (MITF-M) for transcriptional activation in the melanogenic process. Tyrosinase (Tyro) is a target gene of MITF-M, and functions as a key enzyme in melanin biosynthesis. Tetrahydroquinoline carboxamide (THQC) was previously screened as an antimelanogenic candidate. In the current study, we evaluated the antimelanogenic activity of THQC in vivo and elucidated a possible mechanism. Topical treatment with THQC mitigated ultraviolet B (UVB)-induced skin pigmentation in guinea pig with decreased messenger RNA (mRNA) and protein levels of melanogenic genes such as MITF-M and Tyro. Moreover, THQC inhibited cAMP-induced melanin production in α-melanocyte-stimulating hormone (α-MSH)- or histamine-activated B16-F0 cells, in which it suppressed the expression of the MITF-M gene at the promoter level. As a mechanism, THQC normalized the protein levels of Pax3, a transcriptional activator of the MITF-M gene, in UVB-exposed and pigmented skin, as well as in α-MSH-activated B16-F0 culture. However, THQC did not affect UVB- or α-MSH-induced phosphorylation (activation) of CREB. The results suggest that suppression of the Pax3–MITF-M axis might be a potential strategy in the treatment of skin pigmentary disorders that are at high risk under UVB radiation. |
format | Online Article Text |
id | pubmed-7766340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77663402020-12-28 Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide Choi, Yong-Pyo Kim, Ga Hyun Kim, Song-Hee Maeng, Jongseo Lee, Heesoon Han, Sang-Bae Kim, Ki Ho Kim, Youngsoo Int J Mol Sci Article Paired box gene 3 (Pax3) and cAMP responsive element-binding protein (CREB) directly interact with the cis-acting elements on the promoter of microphthalmia-associated transcription factor isoform M (MITF-M) for transcriptional activation in the melanogenic process. Tyrosinase (Tyro) is a target gene of MITF-M, and functions as a key enzyme in melanin biosynthesis. Tetrahydroquinoline carboxamide (THQC) was previously screened as an antimelanogenic candidate. In the current study, we evaluated the antimelanogenic activity of THQC in vivo and elucidated a possible mechanism. Topical treatment with THQC mitigated ultraviolet B (UVB)-induced skin pigmentation in guinea pig with decreased messenger RNA (mRNA) and protein levels of melanogenic genes such as MITF-M and Tyro. Moreover, THQC inhibited cAMP-induced melanin production in α-melanocyte-stimulating hormone (α-MSH)- or histamine-activated B16-F0 cells, in which it suppressed the expression of the MITF-M gene at the promoter level. As a mechanism, THQC normalized the protein levels of Pax3, a transcriptional activator of the MITF-M gene, in UVB-exposed and pigmented skin, as well as in α-MSH-activated B16-F0 culture. However, THQC did not affect UVB- or α-MSH-induced phosphorylation (activation) of CREB. The results suggest that suppression of the Pax3–MITF-M axis might be a potential strategy in the treatment of skin pigmentary disorders that are at high risk under UVB radiation. MDPI 2020-12-17 /pmc/articles/PMC7766340/ /pubmed/33348800 http://dx.doi.org/10.3390/ijms21249631 Text en © 2020 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 Choi, Yong-Pyo Kim, Ga Hyun Kim, Song-Hee Maeng, Jongseo Lee, Heesoon Han, Sang-Bae Kim, Ki Ho Kim, Youngsoo Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide |
title | Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide |
title_full | Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide |
title_fullStr | Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide |
title_full_unstemmed | Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide |
title_short | Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide |
title_sort | suppression of pax3–mitf-m axis protects from uvb-induced skin pigmentation by tetrahydroquinoline carboxamide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766340/ https://www.ncbi.nlm.nih.gov/pubmed/33348800 http://dx.doi.org/10.3390/ijms21249631 |
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