High personal UVR doses can be gained during leisure activities, causing intense self-resolving inflammation (sunburn) of unprotected skin. UVR activates release of membrane fatty acids and upregulates their metabolism by cyclooxygenases (COX) and lipoxygenases (LOX) to different eicosanoids. While COX-derived prostaglandin (PG)E(2) is a potent mediator of sunburn vasodilatation, LOX-derived 15-hydroxyeicosatetraenoic acid (HETE) and its lipoxin metabolites may contribute to sunburn limitation.
View Article and Find Full Text PDFThis study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. Alpha-melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD(2) production in these cells without affecting PGE(2).
View Article and Find Full Text PDFExcessive ultraviolet radiation (UVR) exposure induces erythema, mediated in part by prostaglandin-E(2) (PGE(2)). While keratinocytes are a major PGE(2) source, epidermal melanocytes (EM) also express PGE(2)-production machinery. It is unclear whether EM-produced PGE(2) contributes to UVR-induced skin inflammation, and whether this is correlated with melanogenesis.
View Article and Find Full Text PDFSunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course.
View Article and Find Full Text PDFProopiomelanocortin (POMC) can be processed to ACTH and melanocortin peptides. However, processing is incomplete in some tissues, leading to POMC precursor release from cells. This study examined POMC processing in human skin and the effect of POMC on the melanocortin-1 receptor (MC-1R) and melanocyte regulation.
View Article and Find Full Text PDFThe proopiomelanocortin (POMC)-derived peptides, ACTH and alpha-MSH, are the principal mediators of human skin pigmentation via their action at the melanocortin-1 receptor (MC-1R). Recent data have demonstrated the existence of a functionally active beta-endorphin/mu-opiate receptor system in both epidermal and hair follicle melanocytes, whereby beta-endorphin can regulate melanogenesis, dendricity, and proliferation in these cells. However, a role for ACTH and alpha-MSH in the regulation of the human follicular pigmentary unit has not been determined.
View Article and Find Full Text PDFProstaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2.
View Article and Find Full Text PDFThe pro-opiomelanocortin (POMC)-derived peptides, alpha-melanocyte-stimulating hormone, and adrenocorticotropic hormone, are important mediators of human skin pigmentation via action at the melanocortin-1 receptor. Recent data suggests that such a regulatory role also exists for the endogenous opiate, beta-endorphin (beta-END). A role for this beta-END in the regulation of follicular pigmentation, however, has not been determined.
View Article and Find Full Text PDFReactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) are produced in the skin under the influence of UV radiation. These compounds are highly reactive and can induce DNA lesions in epidermal cells. Melanin is considered to protect human skin against DNA damage by absorbing UV radiation.
View Article and Find Full Text PDFMelanocortin receptor type 1 (MC-1R) is an important control point for ultraviolet ray (UVR)-induced tanning response in the skin. In this study, we show that p-locus is a downstream target for MC-1R signaling. The expression of p-locus was up-regulated by alpha-MSH as well as db-cAMP, a synthetic analogue of cAMP that mimics activation of MC-1R.
View Article and Find Full Text PDFbeta-Endorphin is an opioid peptide cleaved from the precursor pro-hormone pro-opiomelanocortin, from which other peptides such as adrenocorticotropic hormone, beta-lipotropic hormone, and alpha-melanocyte-stimulating hormone are also derived. alpha-Melanocyte-stimulating hormone and adrenocorticotropic hormone are well documented to regulate human skin pigmentation via action at the melanocortin-1 receptor. Whereas plasma beta-endorphin is reported to increase after exposure to ultraviolet radiation, to date a functional role for beta-endorphin in the regulation of human epidermal melanocyte biology has not been demonstrated.
View Article and Find Full Text PDFGeneralized vitiligo is an autoimmune disorder characterized by acquired white patches of skin and overlying hair, the result of loss of melanocytes from involved areas. The most common disorder of pigmentation, vitiligo occurs with a frequency of 0.1-2.
View Article and Find Full Text PDFWe have examined whether melanin affects Ca2+ homeostasis in cultured normal human melanocytes. Intracellular Ca2+ concentrations ([Ca2+]i), were measured in four Caucasian and in three Negroid melanocyte cultures. Under resting conditions [Ca2+]i was around 100 nM in all cultures, but differences between cells within cultures were observed.
View Article and Find Full Text PDFBiochem Biophys Res Commun
August 2002
In this study, we have demonstrated the presence of melanin-concentrating hormone (MCH) and melanin-concentrating hormone receptor (MCHR1) transcripts in human skin. Sequence analysis confirmed that the transcripts of both genes were identical to those previously found in human brain. In culture, endothelial cells showed pro-MCH expression whereas no signal was found in keratinocytes, melanocytes, and fibroblasts.
View Article and Find Full Text PDFMelanocytes are cells of neural crest origin. In the human epidermis, they form a close association with keratinocytes via their dendrites. Melanocytes are well known for their role in skin pigmentation, and their ability to produce and distribute melanin has been studied extensively.
View Article and Find Full Text PDFThe melanocortins are involved in the regulation of various cognitive and physiological processes such as learning, feeding, immune suppression, pigmentation, and sebum production. Five melanocortin receptors have been identified, of which the melanocortin 5 receptor (MC5R) has the most widespread distribution. This subtype is found in the brain, and at numerous peripheral sites including the skin where it is expressed in the sebaceous glands.
View Article and Find Full Text PDFThe skin pigment melanin is produced in melanocytes in highly specialized organelles known as melanosomes. Melanosomes are related to the organelles of the endosomal/lysosomal pathway and can have a low internal pH. In the present study we have shown that melanin synthesis in human pigment cell lysates is maximal at pH 6.
View Article and Find Full Text PDFAdrenal phaeochromocytoma rarely causes ectopic ACTH syndrome. We describe a 44-yr-old hypertensive woman who was Cushingoid and markedly pigmented. Laboratory studies indicated severe hypokalaemia, abnormal liver function tests, and random serum cortisols greater than 1660 nmol/L.
View Article and Find Full Text PDFThe melanocortin 1 (MC-1) receptor is a key control point in the regulation of skin pigmentation. Alpha-MSH is an agonist at this receptor and through its activation regulates melanocyte function. alpha-MSH is cleaved from pro-opiomelanocortin (POMC) in the pituitary, but in humans the skin is a more important source of the peptide.
View Article and Find Full Text PDFIn this study, we describe the activation of melanogenesis by selective vacuolar type H(+)-ATPase inhibitors (bafilomycin A1 and concanamycin A) in amelanotic human and mouse melanoma cells which express tyrosinase but show no melanogenesis. Addition of the inhibitors activated tyrosinase within 4 h, and by 24 h the cells contained measurable amounts of melanin. These effects were not inhibited by cycloheximide (2 microgram/ml) which is consistent with a post-translational mechanism of activation.
View Article and Find Full Text PDFalpha-MSH, has numerous actions in the skin and by activating the MC1 receptor (MC1-R) on melanocytes it stimulates melanogenesis. Rather than producing large increase in melanin production alpha-MSH acts specifically to stimulate eumelanin synthesis. Although this could be important in determining skin color and tanning there is debate as to the pigmentary significance of alpha-MSH in humans.
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