Dopamine-induced apoptosis in human melanocytes involves generation of reactive oxygen species
Journal
British Journal of Dermatology
Journal Volume
154
Journal Issue
6
Pages
1071-1079
Date Issued
2006
Author(s)
Abstract
Background: Previous studies have shown that significant increases in urinary and plasma levels of several monoamines and their metabolites characterize the onset of vitiligo and its progression. Recently, both epidermal keratinocytes and melanocytes were found to have the capacity for the biosynthesis of several catecholamines and serotonin. Some monoamines and their metabolites can induce apoptosis and cytotoxicity in neural cells. However, no previous report has investigated the potential role of these monoamines in inducing apoptosis or cytotoxicity in melanocytes. Objectives: To study the effects of dopamine (DA), norepinephrine (NE), epinephrine (EP), and serotonin (5-HT) on melanocyte cytotoxicity and apoptosis. Methods: Primary cultures of normal human melanocytes established from the foreskins of normal individuals were treated with different concentrations of DA, NE, EP and 5-HT for 5 and 7 days. Cell viability was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] assay. Melanocyte apoptosis was evaluated by morphological examination and flow cytometric analysis. We also measured the generation of reactive oxygen species (ROS) after DA treatment. Results: Among the four monoamines used in this study, only DA had an effect, dose-dependently decreasing the melanocyte viability at concentrations ranging from 0·01 to 100 μmol L-1 (0·1 and 1 μmol L-1, P < 0·05; 10 μmol L-1, P < 0·01). In addition, DA-induced melanocyte apoptosis was evidenced by the increased percentage of sub-G1 cells from 7·71 ± 0·28% (control) to 12·22 ± 1·05% (0·1 μmol L-1 DA) (P < 0·005), and treatment with the antioxidant N-acetylcysteine (NAC) reversed this apoptotic effect. DA treatment led to the generation of ROS, which could be prevented by pretreatment with NAC. Conclusions: DA can induce melanocyte apoptosis, which might be related to the generation of ROS. This novel effect might play an important role in the development or progression of vitiligo, which is currently viewed as a disease process closely related to melanocyte apoptosis. ? 2006 British Association of Dermatologists.
Other Subjects
3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide; acetylcysteine; adrenalin; dopamine; monoamine; noradrenalin; reactive oxygen metabolite; serotonin; apoptosis; article; cell culture; cell structure; cell viability; controlled study; cytotoxicity; dose response; flow cytometry; human; human cell; melanocyte; prepuce; priority journal; vitiligo; Acetylcysteine; Apoptosis; Cell Survival; Cells, Cultured; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Epinephrine; Humans; Male; Melanocytes; Norepinephrine; Reactive Oxygen Species; Serotonin
Type
journal article