Abstract
Mlph plays a crucial role in regulating skin pigmentation through the melanosome transport process. Although Mlph is a major component involved in melanosome transport, the mechanism that regulates the expression of the Mlph gene has not been identified. In this study, we demonstrate that Mlph expression is regulated by the glucocorticoid receptor (GR). Alteration of GR activity using a specific GR agonist or antagonist only regulated the expression of Mlph among the 3 key melanosome transport proteins. Translocation of GR from the cytosol into the nucleus following Dex treatment was confirmed by separating the cytosol and nuclear fractions and by immunofluorescence staining. In ChIP assays, Dex induced GR binding to the Mlph promoter and we determined that Dex induced the GR binding motif on the Mlph promoter. Our findings contribute to understanding the regulation of Mlph expression and to the novel role of GR in Mlph gene expression.
Highlights
Melanosomes are unique organelles where melanin pigments are synthesized and stored by maturation during transport[1]
We previously reported that 2-methylnaphtho[1,2,3-de]quinolin-8-one (MNQO) and 16-kauren-2beta-18,19triol 16-kauren inhibit the expression of melanosome transport proteins, inhibiting skin pigmentation in human artificial skin and guinea pig skin models[30, 31] MNQO repressed the expression of Rab27a, Mlph and MyoVa while 16-kauren reduced Mlph expression, which led to the inhibition of pigmentation
Most melanosome aggregation disappeared when melanocytes were cultured with Dex, and the melanosomes of Dex-treated Melan-a melanocytes were distributed in the whole cell body compared with melanocytes preexposed to RU486 or cultured in serum-free medium (Fig. 1)
Summary
Melanosomes are unique organelles where melanin pigments are synthesized and stored by maturation during transport[1]. That study suspected that the increased level of Mlph (by aldosterone) may increase epithelial Na + channel (ENaC) trafficking and promote melanosome transport, that group used different cells (cortical collecting duct cells rather than melanocytes) and did not confirm melanosome distribution or the expression of other melanosome transport proteins. We used serum-free medium or charcoal-stripped serum in the culture medium to prevent the effects of undefined levels of cortisol in the serum. The exception to this was the use of FBS during subculture of melanocytes to maintain their high growth rates. The mechanism that regulates Mlph gene expression in melanocytes is not well understood
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