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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...

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Autores principales: Choi, Yong-Pyo, Kim, Ga Hyun, Kim, Song-Hee, Maeng, Jongseo, Lee, Heesoon, Han, Sang-Bae, Kim, Ki Ho, Kim, Youngsoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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