title: Up-regulation of melanin synthesis by the antidepressant fluoxetine.
abstract: Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase (TYR) activity, enhances the protein levels of microphthalmia-associated transcription factor (MITF), TYR and tyrosinase-related protein-1 (TRP-1) and eventually leads to a dramatic increase in melanin production in both murine B16F10 melanoma cells and normal human melanocytes (NHMCs). In well-characterized C57BL/6 mouse models, systemic application of fluoxetine increased hair pigmentation by up-regulating hair follicular MITF, TYR, TRP-1 and tyrosinase-related protein-2 (TRP-2) protein levels. Using a serotonin 1A receptor (SR1A) antagonist and RNA interference (RNAi) technique, we revealed that SR1A appears to be one of the involved pathways in the fluoxetine-induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR1A may serve as a novel target in modulating melanogenesis.
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors: Sha
authors: S
authors: Liao
authors: Jing
authors: J
authors: Shang
authors: Xiaoli
authors: X
authors: Tian
authors: Xueqi
authors: X
authors: Fan
authors: Xiupu
authors: X
authors: Shi
authors: Siran
authors: S
authors: Pei
authors: Qian
authors: Q
authors: Wang
authors: Boyang
authors: B
authors: Yu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011257:Pregnancy Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D007370:Interferon Type I; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D011257:Pregnancy Proteins; C020947:interferon tau; D005473:Fluoxetine; D014442:Monophenol Monooxygenase