Inhibitory effect of 2-methyl-naphtho[1,2,3-de]quinolin-8-one on melanosome transport and skin pigmentation

Jong Il Park,Jae Sung Hwang,Ha Yeon Lee,Ji Eun Lee,Cheol Hwan Myung

doi:10.1038/srep29189

Abstract

Melanosomes are lysosome-related organelles with specialized capabilities of melanin synthesis and movement mediated by the Rab27a-Melanophilin-MyosinVa protein complex. In this study, we found that 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO) induced melanosome aggregation around the nucleus in melan-a melanocytes and in melan-a melanocytes/SP-1 keratinocyte co-cultures without inducing toxicity or changing the melanin content. Western blot and real-time PCR analyses showed that MNQO decreased expression of the Rab27a, Melanophilin and MyosinVa proteins and mRNAs, respectively, in melan-a melanocytes. In a reconstituted human epidermis model, treatment with 0.001% MNQO reduced skin pigmentation. Also, MNQO reduced skin pigmentation in brown guinea pigs induced by UVB irradiation. These results indicated that regulation of melanosome transport may serve as a good target for new skin depigmenting agents and MNQO itself could be a candidate.

Highlights

Pigmentation in reconstituted human epidermis and brown guinea pig in vivo
We observed that MNQO inhibited melanosome transport in monolayer cultures of melan-a melanocytes and in co-cultures consisting of SP-1 keratinocytes and melan-a melanocytes
Melanosome clustering was observed in a co-culture system composed of SP-1 keratinocytes and melan-a melanocytes treated with 10 μM MNQO

Summary

Introduction

Pigmentation in reconstituted human epidermis and brown guinea pig in vivo. We investigated the inhibitory mechanism of MNQO on melanosome transport in melanocytes. Results Effect of MNQO on the perinuclear localization of melanosomes and melanin synthesis in melan-a melanocytes. To test the effects of MNQO treatment on melanin synthesis in melan-a melanocytes, melanin content was measured in cells treated with MNQO at 2 μM, 10 μMand 20 μMfor 72 h (Fig. 2D). MNQO induced perinuclear melanosome aggregation, but did not change melanin content in melan-a melanocytes.

Results

Conclusion