Dopamine-induced apoptosis in human melanocytes involves generation of reactive oxygen species

Authors: Chu, C-Y.; Liu, Y-L.; Chiu, H-C.; Jee, S-H.

Source: British Journal of Dermatology, Volume 154, Number 6, June 2006 , pp. 1071-1079(9)

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Abstract:

Summary 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.

Keywords: antioxidant; apoptosis; dopamine; melanocyte; monoamine; reactive oxygen species

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2133.2006.07293.x

Affiliations: 1: Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan

Publication date: 2006-06-01

Dopamine-induced apoptosis in human melanocytes involves generation of reactive oxygen species

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