Serum selenium levels and blood glutathione peroxidase activities in vitiligo

It has recently been shown that patients with vitiligo can accumulate epidermal hydrogen peroxide (H2O2) in association with low catalase levels. This study examined serum selenium levels and blood glutathione peroxidase activities in 61 patients and controls. The results showed high serum selenium levels in 56% of the patients. As at least one isoform of glutathione peroxidase requires selenium for its activity, enzyme activities were also evaluated. The overall results were not significantly different compared with controls, but further age‐related analysis of the data indicated significantly lower activities in patients up to 46 years. As glutathione peroxidase can also efficiently degrade H2O2, the results of this study could indicate an additional impaired H2O2 metabolism in vitiligo

Hydrogen peroxide-mediated oxidative stress disrupts calcium binding on calmodulin: more evidence for oxidative stress in vitiligo

NoPatients with acute vitiligo have low epidermal catalase expression/activities and accumulate 10 -3 M H 2O 2. One consequence of this severe oxidative stress is an altered calcium homeostasis in epidermal keratinocytes and melanocytes. Here, we show decreased epidermal calmodulin expression in acute vitiligo. Since 10 -3M H 2O 2 oxidises methionine and tryptophan residues in proteins, we examined calcium binding to calmodulin in the presence and absence of H 2O 2 utilising 45calcium. The results showed that all four calcium atoms exchanged per molecule of calmodulin. Since oxidised calmodulin looses its ability to activate calcium ATPase, enzyme activities were followed in full skin biopsies from lesional skin of patients with acute vitiligo (n = 6) and healthy controls (n = 6). The results yielded a 4-fold decrease of ATPase activities in the patients. Computer simulation of native and oxidised calmodulin confirmed the loss of all four calcium ions from their specific EF-hand domains. Taken together H 2O 2-mediated oxidation affects calcium binding in calmodulin leading to perturbed calcium homeostasis and perturbed L-phenylalanine-uptake in the epidermis of acute vitiligo

Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin.

The participation of (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4) in regulating the tyrosine supply for melanin biosynthesis was investigated by the examination of human keratinocytes, melanocytes, and epidermal suction blisters from normal human skin and from patients with the depigmentation disorder vitiligo. Cells, as well as total epidermis, contained high phenylalanine hydroxylase activities and also displayed the capacity to synthesize and recycle 6-BH4, the essential cofactor for this enzyme in vitiligo, 4a-hydroxy-BH4 dehydratase activity was extremely low or absent, yielding an accumulation of the nonenzymatic by-product 7-tetrahydrobiopterin (7-BH4) at concentrations up to 8 x 10-6 M in the epidermis. This by- product is a potent competitive inhibitor in the phenylalanine hydroxylase reaction with an inhibition constant of 10-6 M. Thus, 6-BH4 seems to control melanin biosynthesis in the human epidermis, whereas 7-BH4 may initiate depigmentation in patients with vitiligo