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https://hdl.handle.net/10495/41091| Título : | NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism |
| Autor : | Bedoya Berrío, Gabriel de Jesús Ruíz Linares, Andrés Rachmin, Inbal Adhikari, Kaustubh Pardo, Luba M. Lee, Ju Hee McConnell, Alicia M. Kato, Shinichiro Fan, Shaohua Kawakami, Akinori Suita, Yusuke Wakamatsu, Kazumasa Igras, Vivien Zhang, Jianming Navarro, Paula P Makhlouta Lugo, Camila R Noonan, Haley Christie, Kathleen A. Itin, Kaspar Mujahid, Nisma Lo, Jennifer V. Hyun Won, Chong Evans, Conor L. Yu Weng, Qing Wang, Hequn Osseiran, Sam Lovas, Alyssa Németh, István Cozzio, Antonio Navarini, Alexander A. Hsiao, Jennifer J. Nguyen, Nhu Kemény, Lajos V. Iliopoulos, Othon Berking, Carola Ruzicka, Thomas Gonzalez-José, Rolando Bortolini, Maria Cátira Canizales Quinteros, Samuel Acuna Alonso, Víctor Gallo, Carla Poletti, Giovanni Rothhammer, Francisco Ito, Shosuke Schiaffino, Maria Vittoria Chao, Luke H. Kleinstiver, Benjamin P. Tishkoff, Sarah Zon, Leonard I. Nijsten, Tamar Allouche, Jennifer Fisher, David E Roider, Elisabeth |
| metadata.dc.subject.*: | Cell Line Línea Celular Cohort Studies Estudios de Cohortes Cyclic AMP AMP Cíclico DNA Damage Daño del ADN Enzyme Inhibitors Inhibidores Enzimáticos Genetic Predisposition to Disease Predisposición Genética a la Enfermedad Melanocytes Melanocitos Melanosomes Melanosomas Mice, Inbred C57BL Ratones Endogámicos C57BL Microphthalmia-Associated Transcription Factor Factor de Transcripción Asociado a Microftalmía Mitochondria Mitocondria Monophenol Monooxygenase Monofenol Monooxigenasa NADP Transhydrogenases NADP Transhidrogenasas Oxidation-Reduction Oxidación-Reducción Polymorphism, Single Nucleotide Polimorfismo de Nucleótido Simple Proteasome Endopeptidase Complex Complejo de la Endopetidasa Proteasomal Proteolysis Proteólisis RNA, Messenger ARN Mensajero Skin Pigmentation Pigmentación de la Piel Ubiquitin Ultraviolet Rays Rayos Ultravioletas Ubiquitina https://id.nlm.nih.gov/mesh/D002460 https://id.nlm.nih.gov/mesh/D015331 https://id.nlm.nih.gov/mesh/D000242 https://id.nlm.nih.gov/mesh/D004249 https://id.nlm.nih.gov/mesh/D004791 https://id.nlm.nih.gov/mesh/D020022 https://id.nlm.nih.gov/mesh/D008544 https://id.nlm.nih.gov/mesh/D020460 https://id.nlm.nih.gov/mesh/D008810 https://id.nlm.nih.gov/mesh/D051739 https://id.nlm.nih.gov/mesh/D008928 https://id.nlm.nih.gov/mesh/D014442 https://id.nlm.nih.gov/mesh/D009250 https://id.nlm.nih.gov/mesh/D010084 https://id.nlm.nih.gov/mesh/D020641 https://id.nlm.nih.gov/mesh/D046988 https://id.nlm.nih.gov/mesh/D059748 https://id.nlm.nih.gov/mesh/D012333 https://id.nlm.nih.gov/mesh/D012880 https://id.nlm.nih.gov/mesh/D025801 https://id.nlm.nih.gov/mesh/D014466 |
| Fecha de publicación : | 2021 |
| Editorial : | Cell Press Elsevier |
| Citación : | Allouche J, Rachmin I, Adhikari K, Pardo LM, Lee JH, McConnell AM, Kato S, Fan S, Kawakami A, Suita Y, Wakamatsu K, Igras V, Zhang J, Navarro PP, Lugo CM, Noonan HR, Christie KA, Itin K, Mujahid N, Lo JA, Won CH, Evans CL, Weng QY, Wang H, Osseiran S, Lovas A, Németh I, Cozzio A, Navarini AA, Hsiao JJ, Nguyen N, Kemény LV, Iliopoulos O, Berking C, Ruzicka T, Gonzalez-José R, Bortolini MC, Canizales-Quinteros S, Acuna-Alonso V, Gallo C, Poletti G, Bedoya G, Rothhammer F, Ito S, Schiaffino MV, Chao LH, Kleinstiver BP, Tishkoff S, Zon LI, Nijsten T, Ruiz-Linares A, Fisher DE, Roider E. NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism. Cell. 2021 Aug 5;184(16):4268-4283.e20. doi: 10.1016/j.cell.2021.06.022. Epub 2021 Jul 6. |
| Resumen : | ABSTRACT: Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes. |
| metadata.dc.identifier.eissn: | 1097-4172 |
| ISSN : | 0092-8674 |
| metadata.dc.identifier.doi: | 10.1016/j.cell.2021.06.022 |
| Aparece en las colecciones: | Artículos de Revista en Ciencias Exactas y Naturales |
Ficheros en este ítem:
| Fichero | Descripción | Tamaño | Formato | |
|---|---|---|---|---|
| BedoyaGabriel_2021_NNT_UVB_MITF.pdf | Artículo de investigación | 7.45 MB | Adobe PDF | Visualizar/Abrir |
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