1-Phenyl-3-(2-thiazolyl)-2-thiourea inhibits melanogenesis via a dual-action mechanism.
1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) is a well-characterized dopamine β-hydroxylase inhibitor that prevents 6-hydroxydopamine-induced degenerative neuronal disease. However, the effect of PTTU on melanogenesis has not been reported. In this study, we examined the effect of PTTU on melanogenesis and studied its mechanism of action. We found that PTTU decreased melanin biosynthesis in a dose-dependent manner in normal human epidermal melanocytes (NHEMs). PTTU also inhibited tyrosinase catalytic activity in NHEMs. Moreover, PTTU treatment led to reduced protein levels of tyrosinase in NHEMs, while the protein levels of tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor were not affected. However, PTTU treatment did not affect the mRNA expression of tyrosinase. We found that PTTU-accelerated tyrosinase degradation via the ubiquitin-dependent proteasome pathway. In summary, we found that PTTU decreased melanin biosynthesis by decreasing the enzymatic activity and stability of tyrosinase. Our results indicate that PTTU could be used as a depigmentation agent for hyperpigmentation disorder.
Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
Yong Hyun
YH
Kim
Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
Jong Il
JI
Park
Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
Cheol Hwan
CH
Myung
Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
Ji Eun
JE
Lee
Department of Dermatology and Research Institute of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Seunghyun
S
Bang
Department of Dermatology and Research Institute of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. csesnumd@gmail.com.
Sung Eun
SE
Chang
Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea. jshwang@khu.ac.kr.
Jae Sung
JS
Hwang
D002478:Cells, Cultured; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010668:Phenylthiazolylthiourea / Q000494:pharmacology*; D012880:Skin Pigmentation / Q000187:drug effects
D008543:Melanins; D010668:Phenylthiazolylthiourea; D004299:Dopamine beta-Hydroxylase; D014442:Monophenol Monooxygenase
1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU); Normal human epidermal melanocyte; Tyrosinase; Ubiquitin proteasome-mediated degradation