Serotoninergic and melatoninergic systems are fully expressed in human skin

Słomiński, Andrzej; Pisarchik, Alexander; Semak, Igor; Sweatman, Trevor W.; Wortsman, Jacobo; Szczesniewski, Andre; Slugocki, George; McNulty, John A.; Kauser, Söbia; Tobin, Desmond J.; Chen, Jing; Johansson, Ӧlle

doi:10.1096/fj.01-0952fje

Cited by 250 publications

(293 citation statements)

References 48 publications

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“…In addition, its receptor-independent activity suggests that melatonin could also have a protective role against UV-induced pathology [42,43,65]. Both biosynthetic and biodegradative pathways for melatonin have been initially characterized in whole human skin and in melanoma cells [42,43,66,67].…”

Section: Melatonin Receptorsmentioning

confidence: 99%

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Carlson

Linette

Aplin

et al. 2007

Dermatologic Clinics

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Melanocytes are an intraepidermal population of dendritic cells responsible for the production of melanin, a pigment that varies from yellow to brown to black pigment that after transfer to neighboring keratinocytes acts both as an endogenous screen and a buffering system against harmful ultraviolet (UV) wavelengths in sunlight [1]. Skin pigmentation has both individual and societal implications. The cosmetic desire for increased pigmentation (tanning) has resulted in many deleterious alterations including hastened skin ageing with wrinkles and poikiloderma and an increase in lentigines, melanocytic nevi, and melanoma. Focal or widespread loss of normal pigmentation not only renders individuals extraordinarily vulnerable to the harmful effects of sunlight (eg, increased risk of skin cancer in albinism), but it can also result in severe emotional stress and, in some societies, ostracism and discrimination (eg, vitiligo).Melanocytes are derived from the neural crest and are located along the basal layer of the epidermis and within the hair follicle, predominately the basal layer of the hair bulb matrix [1,2]. By the 50th day of intrauterine life, melanocytes can be detected in the epidermis; their migration to the epidermis and survival is dependent on receptor tyrosine kinase (RTK) c-Kit and its ligand stem cell factor (SCF) within the epidermis [3,4]. Mutations of the c-Kit gene lead to patches of hypopigmentation caused by lack of melanocyte migration, termed piebaldism [5]. Another important signaling molecule in melanocyte migration and development is Wnt5a, which signals via the Frizzled-5 receptor [6]. Overexpression of Wnt5a/ Frizzled is found in melanomas and associated with increased cell motility and invasiveness [7,8].Skin keratinocytes obtain melanin pigment from melanocytes, and keratinocytes provide the necessary microenvironment for melanocyte survival, proliferation, differentiation, and migration via production of ligands that interact with melanocyte receptors [1,[9][10][11] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript epidermal melanin unit denotes the symbiotic relationship between one melanocyte transporting melanin via its dendritic processes to approximately 36 keratinocytes [10]. Melanocytes are located on the basement membrane among basal keratinocytes at ratio of 1 melanocyte per 5 basal keratinocytes in hematoxylin and eosin-stained histologic sections. This balance is maintained through regulated induction of melanocyte division. During childhood as the skin surface expands, throughout adulthood to maintain melanocyte numbers, and in response to exposure to sunlight or skin wounding, melanocytes are stimulated to proliferate at a low rate. Melanocyte proliferation entails uncoupling from keratinocytes, loss of their dendrites, cell division, migration along the basement membrane, then recoupling with keratinocytes to form the epidermal melanin unit. Keratinocytes regulate melanocyte growth and expression of melanocyte cell surface receptors via cell adhes...

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Section: Melatonin Receptorsmentioning

confidence: 99%

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Carlson

Linette

Aplin

et al. 2007

Dermatologic Clinics

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“…Increasing evidence in the field suggests that melatonin acts at many extrapineal sites such as the gastrointestinal tract (11,12), the blood cell system (13), the retina (14), the bone marrow (15,16) and the skin (17)(18)(19)(20)(21)(22). In the epidermal keratinocytes, a constitutive and UV-induced melatonin metabolism has recently been described (23).…”

Section: Introductionmentioning

confidence: 99%

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Fischer

Żmijewski²,

Zbytek³

et al. 2006

Int J Oncol

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Abstract.Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10 -12 -10 -3 M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor ROR· by RT-PCR. Melatonin at pharmacological concentrations (10 -3 -10 -7 M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10 -12 -10 -10 M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor ROR· including its isoform ROR·4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.

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“…In nature, changes in the length of the light period are translated into changes in the plasma melatonin and prolactin levels which can trigger animals to produce a longer/shorter or whiter/darker coat to improve their chances for survival during a given season (Rose et al 1987). Now that we know that human and rodent skin and hair follicles are extra-pituitary sites of melatonin synthesis (Slominski et al 2002(Slominski et al , 2003Kobayashi et al 2005), one wonders to which extent environmental cues (such as the length of the light period) can also affect seasonal changes in skin and skin appendage patterns.…”

Section: Environmental Based Pattern Changesmentioning

confidence: 99%

Distinct mechanisms underlie pattern formation in the skin and skin appendages

Widelitz

Baker²,

Plikus

et al. 2006

Birth Defects Research Pt C

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SummaryPatterns form with the break of homogeneity, leading to the emergence of new structure or arrangement. There are different physiological and pathological mechanisms which lead to the formation of patterns. Here we first introduce the basics of pattern formation and their possible biological basis. We then discuss different categories of skin patterns and their potential underlying molecular mechanisms. Some patterns, such as the lines of Blaschko and naevus, are based on cell lineage and genetic mosaicism. Other patterns, such as regional specific skin appendages, can be set by distinct combinatorial molecular codes, which in turn may be set by morphogenetic gradients. There are also some patterns, such as the arrangement of hair follicles (hair whorls) and fingerprints, which involve genetics as well as stochastic epigenetic events based on physical-chemical principles. Many appendage primordia are laid out in developmental waves. In the adult, some patterns, such as those involving cycling hair follicles, may appear as traveling waves in mutant mice. Since skin appendages can renew themselves in regeneration, their size and shape can still change in the adult via regulation by hormones and the environment. Some lesion patterns are based on pathological changes involving the above processes and can be used as diagnostic criteria in medicine. Understanding the different mechanisms which lead to patterns on the skin will help us appreciate their full significance in morphogenesis and medical research. Much remains to be learned about complex pattern formation, a level between molecular biology and organism phenotypes.

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Serotoninergic and melatoninergic systems are fully expressed in human skin

Cited by 250 publications

References 48 publications

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Distinct mechanisms underlie pattern formation in the skin and skin appendages

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