当前位置: X-MOL 学术J. Invest. Dermatol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Regulation of Melanogenesis by the Amino Acid Transporter SLC7A5.
Journal of Investigative Dermatology ( IF 5.7 ) Pub Date : 2020-03-30 , DOI: 10.1016/j.jid.2020.03.941
Céline Gaudel 1 , Frédéric Soysouvanh 2 , Justine Leclerc 2 , Karine Bille 2 , Chrystel Husser 2 , François Montcriol 3 , Corine Bertolotto 2 , Robert Ballotti 2
Affiliation  

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.



中文翻译:

氨基酸转运蛋白SLC7A5对黑色素生成的调节。

染色质免疫沉淀测序和微阵列数据的集成使我们能够确定先前未报告MITF -靶基因,其中所述氨基酸转运SLC7A5也包括在内。我们报道了小干扰RNA介导的SLC7A5敲低可减少B16F10细胞中的色素沉着,但既不影响形态也不影响树突。SLC7A5处理抑制剂2-氨基-2-降冰片烷羧酸(BCH)或JPH203也会降低B16F10细胞中黑色素的合成。我们的发现表明,BCH与参考型脱色剂曲酸一样有效,但通过另一种途径起作用,而不影响酪氨酸酶的活性。BCH还可以减少人MNT1黑色素瘤细胞或正常人黑色素细胞中的色素沉着。最后,我们使用重建的人表皮在更生理学的模型上测试了BCH,并证实了对色素沉着的强烈抑制作用,揭示了SLC7A5抑制的临床潜力,并将BCH定位为适合色素沉着过度的美容或皮肤病学干预的色素沉着剂。

更新日期:2020-03-30
down
wechat
bug