RRC ID 63228
Author Zhou S, Sakamoto K.
Title Citric acid promoted melanin synthesis in B16F10 mouse melanoma cells, but inhibited it in human epidermal melanocytes and HMV-II melanoma cells via the GSK3β/β-catenin signaling pathway.
Journal PLoS One
Abstract Melanin, a pigment synthesized by melanocytes in the skin, resists the damage caused by ultraviolet rays to cells. Citric acid, a well-known food additive, is commonly used as an antioxidant and is an important part of the tricarboxylic acid (TCA) cycle for energy production during cellular metabolism. Here, we aimed to investigate whether the addition of excess citric acid regulates melanin synthesis, and to delineate the underlying mechanism. First, we observed that citric acid exerts opposite redox effects on mouse and human cells. Interestingly, treatment with excess citric acid increased the melanin content in mouse cells but decreased it in human cells. Furthermore, the expression of factors important for melanin synthesis, such as microphthalmia-associated transcription factor (MITF), was also regulated by citric acid treatment-it was promoted in mouse cells and suppressed in human cells. Citric acid also impacted the upstream regulators of MITF, glycogen synthase kinase 3β (GSK3β), and β-catenin. Second, we determined the importance of GSK3β in the citric acid-mediated regulation of melanin synthesis, using a GSK3β inhibitor (BIO). To the best of our knowledge, this is the first study to show that citric acid regulates melanin synthesis via the GSK3β/β-catenin signaling pathway, and that equal amounts of exogenous citric acid exert opposing effects on mouse and human cells.
Volume 15(12)
Pages e0243565
Published 2020-1-1
DOI 10.1371/journal.pone.0243565
PII PONE-D-20-15037
PMID 33332393
PMC PMC7746170
MeSH Animals Cell Line, Tumor Citric Acid / metabolism Citric Acid / pharmacology* Epidermal Cells / metabolism Epidermis / metabolism Glycogen Synthase Kinase 3 beta / metabolism Humans Melanins / metabolism* Melanocytes / drug effects Melanocytes / metabolism* Melanoma / drug therapy Melanoma / metabolism Melanoma, Experimental / metabolism Mice Microphthalmia-Associated Transcription Factor / metabolism Oxidation-Reduction / drug effects Phosphorylation / drug effects Pigmentation / drug effects Signal Transduction / drug effects beta Catenin / metabolism
IF 2.74
Human and Animal Cells B16F10(RCB2630)