Ceramide melanocyte

Voluntary feed intake is insufficient to meet the nutrient demands associated with late pregnancy in prolific ewes and early lactation in high yielding dairy cows. Under these conditions, peripheral signals such as growth hormone and ceramides trigger adaptations aimed at preserving metabolic well-being. Recent work in rodents has shown that the central nervous system-melanocortin (CNS-MC) system, consisting of alpha-melanocyte stimulating hormone (α-MSH) and agouti-related peptide (AGRP) acting respectively as agonist and antagonist on central MC receptors, contributes to the regulation of some of the same adaptations...

UV radiation inducing mutations in melanocytes might cause melanoma. As changes in lipid composition and metabolism are associated with many types of cancer including skin cancer, we aimed to evaluate the effects of two phytocannabinoids cannabidiol (CBD) and cannabigerol (CBG), on changes in phospholipid and ceramide (CER) profiles induced by UVA irradiation in human melanocytes and melanoma. UVA radiation caused a significant up-regulation PC, PI and SM species and decrease of CERs content in both types of cells, while up-regulation of PEo was only observed in melanocytes...

Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2...

Glucosylceramides (GlcCer), which are present in many edible plants, suppress melanin production in mouse melanocytes. Rice GlcCer consist of multiple molecules that comprise different types of sphingoid bases as well as diverse lengths and stereotypes of free fatty acids. Adjacent to the GlcCer fraction, there are free ceramides (Cer) as minor constituents. However, the anti-melanogenic activities of individual GlcCer and Cer remain unknown. Therefore, we herein isolated 13 GlcCer and elasticamide, a Cer [AP] from the gummy by-products of rice bran oil, and examined their anti-melanogenic activities...

The skin barrier of melasma is involved in the pathogenesis of melasma. Previous studies have shown that there are differences in the expression of epidermal lipid genes in melasma, but little is known about the epidermis lipid composition of melasma. Compared with the non-lesional skin, the content of total lipids, phosphatidic acid, phosphatidylserine, and ceramide (Cer) increased significantly in the lesional skin. Multivariate data analysis indicated that 40 individual Cer lipid species were responsible for the discrimination...

Disturbance of sphingolipid metabolism may represent a novel therapeutic target in metastatic melanoma, the most lethal form of skin cancer. Beta-galactosylceramidase (GALC) removes beta-galactose from galactosylceramide and other sphingolipids. In this study, we show that downregulation of galcb, a zebrafish orthologue of human GALC, affects melanoblast and melanocyte differentiation in zebrafish embryos, suggesting a possible role for GALC in melanoma. On this basis, the impact of GALC expression in murine B16-F10 and human A2058 melanoma cells was investigated following its silencing or upregulation...

To investigate the role of C16:0 ceramide in melanoma metastatic behavior and glycolysis, five common long-chain ceramides (C16:0, C18:0, C20:0, C22:0, C24:0) were tested in melanocyte and melanoma cell lines by LC-MS. We then treated non-metastatic and metastatic melanoma cells with PDMP and exogenous C16:0 to explore their effects on proliferation, migration, and glycolysis. The long-chain ceramide was also analyzed by LC-MS after treatment. C16:0 ceramide showed the highest levels in melanocyte and melanoma cells, with all melanomas higher than melanocytes...

Melanoma is a malignant tumor deriving from neoplastic transformation of melanocytes. The incidence of melanoma has increased dramatically over the last 50 years. It accounts for most cases of skin cancer deaths. Early diagnosis leads to remission in 90% of cases of melanoma; conversely, for melanoma at more advanced stages, prognosis becomes more unfavorable also because dvanced melanoma is often resistant to pharmacological and radiological therapies due to genetic plasticity, presence of cancer stem cells that regenerate the tumor, and efficient elimination of drugs...

Melanoma is the most aggressive form of skin cancer, with metastatic melanoma being refractory to currently available conventional therapies. In this study, we evaluated the inhibitory effect of coronatine (COR) on the proliferation of metastatic melanoma cells. COR inhibited the proliferation of melanoma cells but negligibly affected the proliferation of normal melanocytes. Comparative metabolic and lipidomic profiling using gas chromatography-mass spectrometry and direct infusion-mass spectrometry was performed to investigate COR-induced metabolic changes...

The activity of ABC294640, a small-molecular sphingosine kinase 2 (SphK2) inhibitor, in human skin squamous cell carcinoma (SCC) cells was tested in this study. SphK2 mRNA and protein are expressed in established (A431 cheilocarcinoma cell line) and primary human skin SCC cells. ABC294640 dose-dependently inhibited survival, cell cycle progression and proliferation of skin SCC cells. Furthermore, ABC294640 induced caspase-3/-9 and apoptosis activation in skin SCC cells. The SphK2 inhibitor was however non-cytotoxic to SphK2-null skin melanocytes, keratinocytes and fibroblasts...

WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6 -NBD-cermide and UDP-glucose...

Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes...

Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells...

The oxidized phospholipids (oxPL) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) are generated from 1-palmitoyl-2-arachidonoyl-phosphatidylcholine under conditions of oxidative stress. These oxPL are components of oxidized low density lipoprotein. They are cytotoxic in cells of the arterial wall thus playing an important role in the development and progression of atherosclerosis. The toxic lipid effects include inflammation and under sustained exposure apoptosis...

The recurrent interaction of skin with sunlight is an intrinsic constituent of human life, and exhibits both beneficial and detrimental effects. The apparent robust architectural framework of skin conceals remarkable mechanisms that operate at the interface between the surface and environment. In this Review, we discuss three distinct protective mechanisms and response pathways that safeguard skin from deleterious effects of ultraviolet (UV) radiation. The unique stratified epithelial architecture of human skin along with the antioxidant-response pathways constitutes the important defense mechanisms against UV radiation...

Humans with darkly pigmented skin display superior permeability barrier function in comparison with humans with lightly pigmented skin. The reduced pH of the stratum corneum (SC) of darkly pigmented skin could account for enhanced function, because acidifying lightly pigmented human SC resets barrier function to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes with the extrusion of melanin granules...

In the present study, we observed a marked variation in the expression of PKCα and PKCδ isotypes in B16F10 melanoma tumor cells compared to the normal melanocytes. Interestingly, the tumor instructed expression or genetically manipulated overexpression of PKCα isotype resulted in enhanced G1 to S transition. This in turn promoted cellular proliferation by activating PLD1 expression and subsequent AKT phosphorylation, which eventually resulted in suppressed ceramide generation and apoptosis. On the other hand, B16F10 melanoma tumors preferentially blocked the expression of PKCδ isotype, which otherwise could exhibit antagonistic effects on PKCα-PLD1-AKT signaling and rendered B16F10 cells more sensitive to apoptosis via generating ceramide and subsequently triggering caspase pathway...

A few types of ceramide are reported to decrease melanin synthesis. In the present study, we examined the effects of an artificial ceramide analog, PC102, on melanogenesis using a spontaneously immortalized melanocyte cell line (Mel-Ab). PC102 is currently used as a moisturizing additive in a variety of cosmetics. Our data showed that PC102 inhibited melanin production and tyrosinase activity in a dose-dependent manner, but did not directly affect tyrosinase activity. Microphthalmia-associated transcription factor (MITF), tyrosinase, and β-catenin protein levels decreased after 48 h of PC102 treatment...

Resistance to therapies develops rapidly for melanoma leading to more aggressive disease. Therefore, agents are needed that specifically inhibit proteins or pathways controlling the development of this disease, which can be combined, dependent on genes deregulated in a particular patient's tumors. This study shows that elevated sphingosine-1-phosphate (S-1-P) levels resulting from increased activity of sphingosine kinase-1 (SPHK1) occur in advanced melanomas. Targeting SPHK1 using siRNA decreased anchorage-dependent and -independent growth as well as sensitized melanoma cells to apoptosis-inducing agents...

The sphingolipids, a class of complex bioactive lipids, are involved in diverse cellular functions such as proliferation, differentiation, and apoptosis as well as growth inhibition. Recently sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and C2-ceramide (C2-Cer), sphingolipid containing acetic acid are emerging as melanogenic regulators. A bioactive sphingolipid (PSL) was isolated from hydroalcoholic extract of fresh term human placenta and it induced melanogenesis in an in vitro culture of mouse melanoma B16F10 cells...