Sphingosylphosphorylcholine‐induced ERK activation inhibits melanin synthesis in human melanocytes

Abstract

Sphingosylphosphorylcholine (SPC) is emerging as a potent signaling-lipid mediator. In this study, we investigated the effects of SPC on melanogenesis using cultured human melanocytes. Our results show that SPC significantly inhibits melanin synthesis in a concentration-dependent manner, and further that it reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. SPC treatment was also found to induce short-thick dendrites in human melanocytes, but not to reduce tyrosinase activity in a cell-free system, whereas kojic acid directly inhibited tyrosinase. These results suggest that SPC reduces pigmentation by indirectly regulating tyrosinase. In further experiments, SPC was found to downregulate microphthalmia-associated transcription factor (MITF) and tyrosinase, and Western blotting showed that SPC induces the activations of extracellular signal-regulated kinase (ERK) and 90 kDa ribosomal S6 kinase (RSK-1). Moreover, the specific ERK pathway inhibitor, PD98059, blocked the hypopigmentation effect of SPC, and abrogated the SPC-mediated downregulation of MITF. These results suggest that the ERK pathway is involved in the melanogenic signaling cascade, and that ERK activation by SPC reduces melanin synthesis via MITF downregulation.

Effect of xanthohumol on melanogenesis in B16 melanoma cells

“…However, PKG can increase the expression of tyrosinase protein (Sasaki et al, 2000). Alteration of melanocyte ERK activity by various paracrine cytokines can affect the MITF degradation (Xu et al, 2000;Kim et al, 2006). Induction of p53 increases the expression of hepatocyte nuclear factor-1α, which directly increases the transcription of MITF and tyrosinase (Schallreuter et al, 2003;Schallreuter, 2007).…”

Combination of Amino Acids Reduces Pigmentation in B16F0 Melanoma Cells

“…6,27) Thus, many studies have focused on the regulation of tyrosinase activity in melanoma cells. 28,29) First, we examined the primary effect of 20 aamino acids on melanogenesis in B16F0 melanoma cells. We did not examine the effect of L-tyrosine, because of the poor solubility.…”

Mangosteen leaf extract increases melanogenesis in B16F1 melanoma cells by stimulating tyrosinase activity in vitro and by up-regulating tyrosinase gene expression

“…Excessive accumulation of dopaquinone generated from hydroxylation and oxidation of tyrosine forms dopachrome, which conditionally exhausts cysteine, resulting in accumulation of the black and brownish pigment, eumelanin. Another type of melanin, pheomelanin, is produced through formation of 3-or 5-cysteinyldopa in the presence of cysteine (27)(28)(29). These three enzymes determine the types of melanin to eumelanin or pheomelanin (30).…”

“…Melanosomes contain three types of enzymes: tyrosinase; TRP1; DCT (TRP2) (26). Tyrosinase is a rate-limiting enzyme involved in melanin synthesis that hydroxylates tyrosine, a kind of phenylalanine, to L-3,4-dihydroxyphenylalanine (L-DOPA) and oxidizes L-DOPA to dopaquinone (2,27). Excessive accumulation of dopaquinone generated from hydroxylation and oxidation of tyrosine forms dopachrome, which conditionally exhausts cysteine, resulting in accumulation of the black and brownish pigment, eumelanin.…”

“…An intracellular tyrosinase activity assay was performed as described previously, with slight modifications (13,27). After 48 h, the culture cells were washed with PBS and harvested in RIPA cell lysis buffer supplemented with a protease inhibitor.…”