leupeptins and Hypopigmentation

In this study, the decursin derivative dihydropyranocoumarin D2 (1) was selected for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). The results showed that 1 effectively inhibited melanin synthesis in a concentration-dependent manner, but that it did not inhibit tyrosinase in a cell-free system. In addition, the changes in ERK, Akt, and microphthalmia-associated transcription factor (MITF) in response to treatment with 1 were assessed. The results revealed that ERK was dramatically up-regulated and MITF was down-regulated in response to treatment with 1, but that Akt was unchanged. Therefore, the effects of 1 on melanogenesis were examined in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway). PD98059 restored hypopigmentation and the down-regulation of MITF induced by 1. Finally, MITF down-regulation by 1 was clearly restored by both chloroquine, a lysosomal proteolysis inhibitor, and MG132, a proteasome inhibitor.

Topics: Animals; Benzopyrans; Butyrates; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Hypopigmentation; Leupeptins; Lysosomes; Melanins; Melanocytes; Mice; Microphthalmia-Associated Transcription Factor; Molecular Structure; Monophenol Monooxygenase; Proteasome Inhibitors; Pyranocoumarins