The effects of calcipotriol on the dendritic morphology of human melanocytes under oxidative stress and a possible mechanism: is it a mitochondrial protector?

BACKGROUND

Vitiligo is an acquired pigmentary disorder of unknown etiology that is clinically characterized by the development of white macules in the skin related to the selective loss of melanocytes in those areas. Evidence shows that mitochondria might be a unifying target of reactive oxygen species (ROS) generation, cytokine production, catecholamine release and/or alteration of Ca(2+) metabolism that leads to melanocyte loss.

OBJECTIVE

To assess the protective effect of calcipotriol on mitochondria of human melanocytes by investigating their dendritic morphology under oxidative stress.

METHODS

Human melanocytes were treated with 0.05% H2O2 as well as various concentrations of calcipotriol, after which the retraction velocity of melanocyte dendrites was assessed. Detection of malondialdehyde (MDA) and superoxide dismutase (SOD) was performed as were the mitochondrial membrane potential (MMP) and intracellular calcium concentration ([Ca(2+)]i). Ultrastructural changes of mitochondria in melanocytes were observed by transmission electron microscopy. In addition, the expression of Beclin1, microtubule-associated protein 1 light chain 3 (LC3), dynamin related protein 1 (Drp1), mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), which are related to autophagy and mitochondrial dynamics, were analyzed by Western blot.

RESULTS

Calcipotriol reduced the retraction velocity of melanocyte dendrites. In addition, calcipotriol, from 20nM to 80nM, decreased the level of MDA, increased the activity of SOD, suppressed the reduction of MMP and recovered Ca(2+) homeostasis by reducing [Ca(2+)]i in a concentration-dependent manner. Observation by transmission electron microscopy suggested that calcipotriol might reduce the injury of mitochondria in melanocytes under oxidative stress. Furthermore, the expression of Beclin1, LC3-II/LC3-I, Mfn2 and Drp1 was higher in the calcipotriol-treated melanocytes than in the control or H2O2-treated melanocytes. The level of Mfn1 was almost unchanged, but was higher at a concentration of 80nM calcipotriol than in any other condition. The expression of Mfn2 and Drp1 decreased with increasing calcipotriol concentration.

CONCLUSION

Our study demonstrates the antioxidative effect of calcipotriol on melanocytes against oxidative damage. Moreover, calcipotriol could be a promising drug delivery strategy to protect melanocytes against oxidative damage in vitiligo through autophagy or mitophagy.