RESUMEN
BACKGROUND: 585 nm light-emitting diodes have been proven to suppress melanogenesis in melanocytes. However, whether LEDs will influence normal human epidermal keratinocytes (NHEKs) and paracrine effect of LEDs-irradiated NHEKs in melanogenesis remains unknown. OBJECTIVE: To elucidate the possible mechanisms in vitro of anti-melanogenic activity of 585 nm LEDs on paracrine effect of NHEKs and its exosomes. METHODS: NHEKs irradiated with different fluences of 585 nm LEDs were evaluated the cell viability by CCK8 assay. Irradiated medium of NHEKs was co-cultured with melanocytes. Melanin content, tyrosinase activity and melanogenic enzymes activities were detected. Exosomes from NHEKs medium were isolated and characterized by electron microscopy and nanoparticle tracking analysis. The expression changes of H19 and its encoded exosomal miR-675 were analyzed. RESULTS: Irradiation with 585 nm LEDs from 0 J/cm2 to 20 J/cm2 had no cytotoxic effect on NHEKs. After co-cultured with irradiated medium of NHEKs, melanin content and tyrosinase activity were reduced and the melanogenic activities were downregulated on both mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). H19 and its derived exosomal miR-675 from NHEKs, which has been proven relevant to melanogenesis, were significantly upregulated after irradiation. Furthermore, H19 knockdown and miR-675 inhibition in NHEKs could attenuate the inhibition effect of 585 nm LEDs on melanogenesis. CONCLUSIONS: This study demonstrated that 585 nm LEDs could inhibit melanogenesis via the up-regulation of H19 and its derived exosomal miR-675 from NHEKs, which was considered as a novel paracrine factor in regulating melanogenesis.
Asunto(s)
Hiperpigmentación/terapia , Terapia por Luz de Baja Intensidad/instrumentación , Melaninas/biosíntesis , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Exosomas/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Hiperpigmentación/genética , Queratinocitos/citología , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Terapia por Luz de Baja Intensidad/métodos , Melanocitos/metabolismo , Glicoproteínas de Membrana/metabolismo , MicroARNs/antagonistas & inhibidores , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/metabolismo , Oxidorreductasas/metabolismo , Comunicación Paracrina/genética , Comunicación Paracrina/efectos de la radiación , Cultivo Primario de Células , ARN Largo no Codificante/genética , Semiconductores , Regulación hacia Arriba/genética , Regulación hacia Arriba/efectos de la radiaciónRESUMEN
BACKGROUND: Reticulated acropigmentation of Kitamura (RAPK) is a pigmentary disorder of autosomal dominant inheritance, occurring predominantly within the Japanese population, for which no successful treatment has been described. OBJECTIVE: The objective was to describe a 23-year-old Saudi woman with reticulated acropigmentation of Kitamura (RAPK), who was successfully treated with a 75-nm Q-switched alexandrite laser. METHOD: To report a 23-year-old Saudi woman with reticulated acropigmentation of kitamura (RAPK) who was treated with two sessions of the Q-switched alexandrite laser, six weeks apart with no recurrence after two years. RESULTS: Cutaneous pigmentation of reticulated acropigmentation of kitamura (RAPK) almost resolved completely in two laser sessions. Side effects were limited to transient post inflammatory hypopigmentation. CONCLUSION: Cutaneous pigmentation of reticulated acropigmentation of kitamura (RAPK) can be effectively treated by Q-switched alexandrite (755-nm) laser, which shows a promising result, and it can be considered as treatment option, although further studies are required to confirm the effectiveness of this treatment modality with other Q-switched laser; e.g. Q-switched ND:YAG or Q-switch Ruby.
Asunto(s)
Dermatosis del Pie/radioterapia , Dermatosis de la Mano/radioterapia , Hiperpigmentación/radioterapia , Láseres de Estado Sólido/uso terapéutico , Terapia por Luz de Baja Intensidad , Adulto , Femenino , Humanos , Hiperpigmentación/genética , Adulto JovenRESUMEN
Intracellular cAMP stimulates microphthalmia-associated transcription factor (MITF) induction in melanocytes through cAMP-responsive element binding protein (CREB), which plays a pivotal role in the gene expression of tyrosinase for melanin biosynthesis. In the present study, saucerneol D as a lignan constituent of Saururus chinensis (Saururaceae family) efficiently inhibited melanin production with IC(50) values of 188-297 nM in B16 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or other cAMP elevators. Moreover, saucerneol D down-regulated α-MSH-induced gene expression of tyrosinase at the transcription level in B16 cells, but it did not directly inhibit the catalytic activity of cell-free tyrosinase. As to the molecular basis of hypopigmenting action, saucerneol D inhibited α-MSH-induced phosphorylation of CREB in the cells, and sequentially suppressed MITF induction. Taken together, this study provides saucerneol D down-regulated the gene expression of tyrosinase, resulting in the inhibition of cAMP-induced melanin biosynthesis, and suggests pharmacological potential of the lignan structure in skin hyperpigmentation.
Asunto(s)
AMP Cíclico/metabolismo , Lignanos/farmacología , Melaninas/biosíntesis , Melanocitos/metabolismo , Supervivencia Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación hacia Abajo , Evaluación Preclínica de Medicamentos , Expresión Génica , Hormonas/metabolismo , Hormonas/farmacología , Humanos , Hiperpigmentación/tratamiento farmacológico , Hiperpigmentación/genética , Hiperpigmentación/metabolismo , Lignanos/química , Lignanos/aislamiento & purificación , Luciferasas/metabolismo , Melaninas/genética , Melanoma/tratamiento farmacológico , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Factor de Transcripción Asociado a Microftalmía/antagonistas & inhibidores , Factor de Transcripción Asociado a Microftalmía/genética , Monofenol Monooxigenasa/genética , Monofenol Monooxigenasa/metabolismo , Fosforilación , Saururaceae , alfa-MSH/metabolismo , alfa-MSH/farmacologíaRESUMEN
Familial glucocorticoid deficiency (FGD) or hereditary unresponsiveness to adrenocorticotropin (ACTH) is an autosomal recessive disorder characterized by isolated glucocorticoid deficiency associated with normal mineralocorticoid secretion. Mutations in genes encoding either ACTH receptor or melanocortin 2 receptor accessory protein are responsible for the disease in about 50% of cases, named FGD type 1 and type 2, respectively. Patients may present with hyperpigmentation, recurrent infections, failure to thrive, hypoglycemic seizures, and coma in infancy or early childhood. Here we report the case of a 17-day-old newborn diagnosed with FGD type 1 who presented with hyperbilirubinemia and hyperpigmentation, a sign which was erroneously assumed to be due to prolonged phototherapy by the referring physician. Hormone analysis showed low cortisol and high ACTH levels with normal serum electrolytes and renin-aldosterone axis. Genetic analysis revealed a novel homozygous melanocortin 2 receptor mutation p.Leu225Arg in the patient. The healthy parents were heterozygous for the mutation.
Asunto(s)
Insuficiencia Suprarrenal/genética , Glucocorticoides/deficiencia , Glucocorticoides/genética , Mutación , Receptor de Melanocortina Tipo 2/genética , Errores Congénitos del Metabolismo Esteroideo/genética , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Insuficiencia Suprarrenal/tratamiento farmacológico , Insuficiencia Suprarrenal/patología , Hormona Adrenocorticotrópica/sangre , Pruebas de Química Clínica , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hidrocortisona/uso terapéutico , Hiperbilirrubinemia/tratamiento farmacológico , Hiperbilirrubinemia/genética , Hiperbilirrubinemia/patología , Hiperpigmentación/tratamiento farmacológico , Hiperpigmentación/genética , Hiperpigmentación/patología , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/genética , Hipoglucemia/patología , Recién Nacido , Masculino , Padres , Errores Congénitos del Metabolismo Esteroideo/tratamiento farmacológico , Errores Congénitos del Metabolismo Esteroideo/patología , UltrasonografíaRESUMEN
A peculiar observation published in 1971 by Chernosky et al. is revisited in this paper. An African American mother and three of her four children (two girls and one boy) had hyperpigmented skin areas arranged along Blaschko's lines. According to the current knowledge of formal genetics, a mendelian mode of transmission can be excluded, and paradominant inheritance is likewise highly unlikely. The unusual family constellation of pigmentary mosaicism can be best explained as an example of monoallelic autosomal expression, a concept that is now well established in the genetics of plants and animals but so far unexplored in human skin disorders. Either the paternal or the maternal allele is randomly inactivated, therefore this mechanism can be taken as an autosomal counterpart of X-chromosome inactivation. Recent studies suggest that 5-10% of autosomal human genes are monoallelically expressed. This theory opens a new field of research in dermatology. Clinicians should consider this new aetiological concept when observing cases of hereditary cutaneous mosaicism that cannot be explained by X-linkage.