PUBLICATION
R-Fluoxetine Increases Melanin Synthesis Through a 5-HT1A/2A Receptor and p38 MAPK Signaling Pathways
- Authors
- Liu, L., Fu, M., Pei, S., Zhou, L., Shang, J.
- ID
- ZDB-PUB-181227-5
- Date
- 2018
- Source
- International Journal of Molecular Sciences 20(1): (Journal)
- Registered Authors
- Shang, Jing
- Keywords
- melanin, r-fluoxetine, zebrafish
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Fluoxetine/pharmacology*
- Melanins/metabolism*
- Melanocytes/cytology
- Melanocytes/drug effects
- Melanocytes/metabolism
- Mice
- Microphthalmia-Associated Transcription Factor/metabolism
- Monophenol Monooxygenase/metabolism
- Phosphorylation/drug effects
- Promoter Regions, Genetic
- Receptor, Serotonin, 5-HT1A/metabolism
- Receptor, Serotonin, 5-HT2A/metabolism
- Selective Serotonin Reuptake Inhibitors/pharmacology*
- Signal Transduction/drug effects*
- Stereoisomerism
- Up-Regulation/drug effects*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- p38 Mitogen-Activated Protein Kinases/metabolism
- PubMed
- 30585252 Full text @ Int. J. Mol. Sci.
Citation
Liu, L., Fu, M., Pei, S., Zhou, L., Shang, J. (2018) R-Fluoxetine Increases Melanin Synthesis Through a 5-HT1A/2A Receptor and p38 MAPK Signaling Pathways. International Journal of Molecular Sciences. 20(1):.
Abstract
Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a racemic mixture and has an anxiolytic effect in rodents. Previously, we have shown that fluoxetine can up-regulate melanin synthesis in B16F10 melanoma cells and normal human melanocytes (NMHM). However, the role of r-fluoxetine and s-fluoxetine, in the regulation of melanin synthesis, is still unknown. Here, we show how r-fluoxetine plays a critical role in fluoxetine enhancing melanogenesis, both in vivo and vitro, by up-regulating tyrosinase (TYR) and the microphthalmia-associated transcription factor (MITF) expression, whereas, s-fluoxetine does not show any effect in the vivo and vitro systems. In addition, we found that r-fluoxetine induced melanin synthesis through the serotonin1A receptor (5-HT1A) and serotonin 2A receptor (5-HT2A). Furthermore, r-fluoxetine increased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), without affecting the phosphorylation of extracellularly responsive kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). These data suggest that r-fluoxetine may be used as a drug for skin hypopigmentation disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping