Regulation of Melanogenesis by the Amino Acid Transporter SLC7A5.
Animals
Carboxylic Acids
/ pharmacology
Cell Line, Tumor
Humans
Large Neutral Amino Acid-Transporter 1
/ genetics
Melanins
/ analysis
Mice
Microphthalmia-Associated Transcription Factor
/ genetics
Norbornanes
/ pharmacology
Pigmentation
/ drug effects
Pyrones
/ pharmacology
RNA, Small Interfering
/ genetics
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
06
12
2019
revised:
26
02
2020
accepted:
09
03
2020
pubmed:
3
4
2020
medline:
7
4
2021
entrez:
3
4
2020
Statut:
ppublish
Résumé
Integration of chromatin immunoprecipitation-sequencing and microarray data enabled us to identify previously unreported MITF-target genes, among which the amino acid transporter SLC7A5 is also included. We reported that small interfering RNA-mediated SLC7A5 knockdown decreased pigmentation in B16F10 cells but neither affected morphology nor dendricity. Treatment with the SLC7A5 inhibitors 2-amino-2-norbornanecarboxylic acid (BCH) or JPH203 also decreased melanin synthesis in B16F10 cells. Our findings indicated that BCH was as potent as reference depigmenting agent, kojic acid, but acted through a different pathway not affecting tyrosinase activity. BCH also decreased pigmentation in human MNT1 melanoma cells or normal human melanocytes. Finally, we tested BCH on a more physiological model, using reconstructed human epidermis and confirmed a strong inhibition of pigmentation, revealing the clinical potential of SLC7A5 inhibition and positioning BCH as a depigmenting agent suitable for cosmetic or dermatological intervention in hyperpigmentation diseases.
Identifiants
pubmed: 32240722
pii: S0022-202X(20)31209-4
doi: 10.1016/j.jid.2020.03.941
pii:
doi:
Substances chimiques
2-amino-2-norbornanecarboxylic acid
0
Carboxylic Acids
0
Large Neutral Amino Acid-Transporter 1
0
Melanins
0
Microphthalmia-Associated Transcription Factor
0
Norbornanes
0
Pyrones
0
RNA, Small Interfering
0
kojic acid
6K23F1TT52
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2253-2259.e4Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.