RESUMEN
Autoimmune, self-destructive, oxidative stress and genetic theories have been proposed for the pathogenesis of vitiligo. Autophagy is essential for cellular homeostasis and is implicated in many pathophysiological conditions such as cancer, response to oxidative stress and autoimmunity. The ultraviolet (UV) radiation resistance-associated gene (UVRAG) activates the Beclin1-PI(3)KC3 complex, promoting autophagy. To evaluate whether UVRAG polymorphisms are associated with non-segmental vitiligo (NSV) patients in a Korean sample, we conducted a case-control association study of 225 NSV patients and 439 matched healthy controls. A total of five single nucleotide polymorphisms (SNPs) of UVRAG were selected for analysis. Among these, two SNPs (rs1458836, rs7933235) showed significant genotypic differences between the NSV patient group and the control group. These two SNPs were located within a strong linkage disequilibrium (LD) block. In addition, the haplotype of the UVRAG polymorphism was associated with NSV. This study suggests a possible association between UVRAG and NSV susceptibility.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Supresoras de Tumor/genética , Vitíligo/etnología , Vitíligo/genética , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana EdadRESUMEN
Chronic ultraviolet (UV) exposure induces photoaging and oxidative stress in the skin. We investigated whether Machilus thunbergii Sieb et Zucc (M. thunbergii) could reduce UV-induced photoaging and oxidative stress in hairless mice. The dorsal skin of hairless mice was treated topically with M. thunbergii for 2 h prior to UV irradiation. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were then measured in skin and/or serum samples. Histological changes in the skin were assessed by hematoxylin-eosin (HE) staining. In addition, proteomes from the skin of hairless mice in each group were analyzed. The thickness of the dorsal skin and epidermis was significantly decreased by M. thunbergii treatment. We also found that MDA levels decreased after M. thunbergii treatment and the SOD levels were increased by M. thunbergii compared with those in the UV-only treated group. Proteomic analysis revealed 17 proteins associated with photoaging. These data indicate that M. thunbergii might have antiphotoaging effects.
Asunto(s)
Antioxidantes/farmacología , Lauraceae , Extractos Vegetales/farmacología , Proteoma/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Animales , Femenino , Malondialdehído/metabolismo , Ratones , Ratones Pelados , Estrés Oxidativo/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Envejecimiento de la Piel/patología , Envejecimiento de la Piel/efectos de la radiación , Superóxido Dismutasa/metabolismo , Rayos Ultravioleta/efectos adversosRESUMEN
Vitiligo is an acquired pigmentary disorder of the skin involving melanocyte dysfunction. It has been reported that melanocyte impairment could be related to increased oxidative stress. The glutathione S-transferases (GSTs) are group of polymorphic enzymes that are important in protection against oxidative stress. To find the relationship between GSTM1 and GSTT1 polymorphisms with vitiligo susceptibility, GSTM1 and GSTT1 (homozygous deletion vs. non-deleted) polymorphisms between vitiligo patients (n=310) and healthy controls (n=549) were analyzed. We observed significant association in null alleles of the GSTM1 (P<0.001, OR=2.048, 95% CI=1.529-2.743). GSTM1 null type was also statistically different between two vitiligo subtypes and controls (Focal P<0.001, OR=2.224, 95% CI=1.499-3.298; Generalized P=0.001, OR=1.974, 95% CI=1.342-2.904). However, no significant association in GSTT1 (P=0.869, OR=1.024, 95% CI=0.775-1.353) was observed with vitiligo. In combined analysis of GSTM1 and GSTT1, both null type and GSTM1/GSTT1 (null/present) group showed significant differences between controls and vitiligo patients. These results suggest that GSTM1 null type might be associated with vitiligo susceptibility in Korean population.
Asunto(s)
Glutatión Transferasa/genética , Vitíligo/epidemiología , Vitíligo/genética , Adulto , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The effect of Ganoderma lucidum extract on glucose uptake was studied in L6 rat skeletal muscle cells. G. lucidum extract increased glucose uptake about 2-fold compared to control. The extract stimulated the activity of phosphatidylinositol (PI) 3-kinase which is a major regulatory molecule in the glucose uptake pathway. About 7-fold increased activity of a PI 3-kinase was observed after treatment with G. lucidum extract, whereas PI 3-kinase inhibitor, LY294002, blocked the G. lucidum extract-stimulated PI 3-kinase activity in L6 skeletal muscle cells. Protein kinase B, a downstream mediator of PI 3-kinase, was also activated by G. lucidum extract. We then assessed the activity of AMP-activated protein kinase (AMPK), another regulatory molecule in the glucose uptake pathway. G. lucidum extract increased the phosphorylation level of both AMPK alpha1 and alpha2. Activity of p38 MAPK, a downstream mediator of AMPK, was also increased by G. lucidum extract. Taken together, these results suggest that G. lucidum extract may stimulate glucose uptake, through both PI 3-kinase and AMPK in L6 skeletal muscle cells thereby contributing to glucose homeostasis.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Glucosa/farmacocinética , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Reishi , Transducción de Señal , Proteínas Quinasas Activadas por AMP , Animales , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Técnicas de Cultivo de Célula , Quinasas Quinasa Quinasa PAM/metabolismo , Complejos Multienzimáticos/metabolismo , Músculo Esquelético/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Regulación hacia ArribaRESUMEN
While the anti-oxidant properties of Punica granatum methanol extract (PGMF) are well documented, little is known concerning the anti-inflammatory effect of Punica granatum. PGMF was pretreated in BV2 microglial cells and cells were stimulated to induce inflammation by lipopolysaccharide (LPS). The effect of PGME on the production and expression of tumor necrosis factor alpha (Tnf, previously known as Tnf alpha) was determined by enzyme-linked immunosorbent assay (ELISA), western blotting, and reverse transcription-polymerase chain reaction (RT-PCR). In addition, the expression of nuclear factor kappa b (Nfkappab) was measured using an electrophoretic mobility shift assay (EMSA). By ELISA, PGME at the concentrations of 1, 5, 10, and 50 microg/ml inhibited Tnf production in LPS-stimulated cells by 30.2, 42.3, 57.6, and 88.4%, respectively, compared to LPS-stimulated cells. The LPS-stimulated Tnf production was reduced with a dose-dependent manner. Immuno blot and RT-PCR analyses revealed that PGME of 5 and 50 microg/ml inhibited the expression of both protein and mRNA levels of Tnf compared to LPS-stimulated cells. EMSA revealed that PGME of 5 and 50 microg/ml blocked the LPS-stimulated activation of Nfkappab. These data suggest that PGME may suppress LPS-stimulated Tnf production through inhibition of Nfkappab in BV2 microglia cells.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Lythraceae/química , Microglía/efectos de los fármacos , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/aislamiento & purificación , Western Blotting , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Electroforesis en Gel de Poliacrilamida , Ensayo de Cambio de Movilidad Electroforética , Ensayo de Inmunoadsorción Enzimática , Inflamación , Lipopolisacáridos/farmacología , Ratones , Microglía/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/biosíntesis , Extractos Vegetales/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
AIM: The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cycle-related, cell growth-related, stress response-related and transcription-related genes. METHODS: We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated (5 mg/mL, 24 h) and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT-PCR. RESULTS: Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F, member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE11A), topoisomerase (DNA) I (TOP1), and FK506 binding protein 12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. CONCLUSION: These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug.
Asunto(s)
Amigdalina/farmacología , Antineoplásicos Fitogénicos/farmacología , Ciclo Celular/genética , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Regulación hacia Abajo , Expresión Génica/efectos de los fármacos , Línea Celular Tumoral , HumanosAsunto(s)
Pueblo Asiatico/genética , Polimorfismo de Nucleótido Simple , Proteínas Tirosina Quinasas Receptoras/genética , Vitíligo/genética , Adulto , Estudios de Casos y Controles , Receptor con Dominio Discoidina 1 , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , República de CoreaRESUMEN
The neuronal theory of the pathogenesis of vitiligo is supported by clinical, ultrastructural and biochemical findings. Cyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is expressed in neuronal tissues, and cyclin-dependent kinase 5 (CDK5) seems to be critically involved in the migration of neuroblasts during early post-natal development. To evaluate whether CDK5RAP1 polymorphisms are associated with vitiligo patients in the Korean population, we conducted a case-control association study of 296 vitiligo patients and 426 healthy controls. A total of two single nucleotide polymorphisms (SNPs) of CDK5RAP1 were investigated. Genotypes were determined by polymerase chain reaction (PCR) and direct sequencing. A synonoymous SNP (rs291700, Thr54Thr) and intron SNP (rs158676) of CDK5RAP1 were associated with onset age of the vitiligo (rs291700, p=0.040 in co-dominant 1 and p=0.036 in overdominant; rs158676, p=0.034 in overdominant). Haplotype (AC) showed a difference between the vitiligo and control groups (p=0.036). These results suggest that CDK5RAP1 may be a risk factor of vitiligo in the Korean population.
Asunto(s)
Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Vitíligo/genética , Adulto , Pueblo Asiatico/genética , Femenino , Humanos , MasculinoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: IH-901 (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginseng saponin metabolite formed by human intestinal bacteria and is known to have antitumor and antimetastatic effects. However, there has been no pharmacokinetic study of IH-901 in human beings. AIM OF THE STUDY: The aim of this study was to investigate the pharmacokinetic differences of IH-901 from fermented and non-fermented ginseng. MATERIALS AND METHODS: To investigate whether the pharmacokinetics of IH-901 differ between fermented and non-fermented ginseng, an open label, randomized, single dose, fasting, two-period, cross-over, pharmacokinetic study was conducted. A total of 24 healthy Korean male volunteers participated in this study. All subjects were allocated into two equal groups and administered 3g of fermented or non-fermented Panax ginseng. Serial blood samples for pharmacokinetic analysis were collected in the 24 h after dosing. Plasma IH-901 concentration was measured by a validated high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters including AUC(t), C(max), and T(max) were calculated by noncompartmental models in the BA-CALC program (KFDA, 2008, 1.0.0, Korea). RESULTS: After oral administration of fermented ginseng, 5 subjects experienced diarrhea. The means of AUC(t) and C(max) were significantly different between the two groups. In the fermented ginseng group, AUC(t) was 2083.09±91.97 ng h/mL, a 15.5-fold increase over that of IH-901 from the non-fermented group (134.50±63.10 ng h/mL), and the mean C(max) was 325.00±91.97 ng/mL in the fermented ginseng group, a 27-fold higher value than that in the non-fermented group (13.88±7.24 ng/mL). T(max) was 3.29±1.00 and 12.04±4.96 h in the fermented and non-fermented group, respectively. CONCLUSIONS: The results of this study showed that the pharmacokinetic parameters of IH-901 from fermented Panax ginseng are different from those of non-fermented ginseng, from which IH-901 is formed by intestinal fermentation.
Asunto(s)
Antineoplásicos Fitogénicos/farmacocinética , Pueblo Asiatico , Bacterias/metabolismo , Fermentación , Intestinos/microbiología , Panax , Preparaciones de Plantas/farmacocinética , Sapogeninas/farmacocinética , Administración Oral , Adulto , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/sangre , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/efectos adversos , Preparaciones de Plantas/sangre , Plantas Medicinales , Reproducibilidad de los Resultados , República de Corea/epidemiología , Sapogeninas/administración & dosificación , Sapogeninas/efectos adversos , Sapogeninas/sangre , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
The aim of this study was to determine whether or not promoter polymorphisms of the class I major histocompatibility complex (HLA-E, HLA-F, and HLA-G) are associated with susceptibility to vitiligo. To identify a possible association with vitiligo, 241 patients with non-segmental vitiligo (NSV) and 395 healthy controls were recruited in this study. Three promoter single nucleotide polymorphisms (SNPs; rs1264459 of HLA-E, rs9258170 of HLA-F, and rs1736936 of HLA-G) were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and direct sequencing. Multiple logistic regression models (co-dominant 1, co-dominant 2, dominant, recessive, and log-additive models) were applied for odds ratios (ORs), 95% confidence intervals (CIs), and P values. To obtain the defined results, P values were recalculated by a Bonferroni correction. After the Bonferroni correction, the genotype of the SNP (rs1736936) of HLA-G was shown to have significant association with NSV (P = 0.045 in the recessive model). The genotype frequencies of the HLA-G SNP (rs1736936) had a significant correlation with the age of onset of NSV (P = 0.016 in the co-dominant 1 model and P = 0.027 in the dominant model). Our results suggest that HLA-G, but not HLA-E and HLA-F, may be associated with susceptibility to NSV in the Korean population.
Asunto(s)
Antígenos HLA-G/genética , Vitíligo/epidemiología , Vitíligo/genética , Adulto , Edad de Inicio , Análisis Mutacional de ADN , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Antígenos de Histocompatibilidad Clase I/genética , Prueba de Histocompatibilidad , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Vitíligo/inmunología , Vitíligo/fisiopatología , Antígenos HLA-ERESUMEN
Pre-B-cell leukemia transcription factor 1 (PBX1), which is located on chromosome 1q23, was recently reported to be associated with type 2 diabetes mellitus. We examined whether single nucleotide polymorphisms (SNPs) of the PBX1 gene are associated with overweight/obesity in a Korean population. We genotyped 66 SNPs in the PBX1 gene and investigated their association with clinical phenotypes found in 214 overweight/obese subjects and 160 control subjects using the Affymetrix Targeted Genotyping chip array. Seven SNPs (g.+75186C>T, g.+78350C>A, g.+80646C>T, g.+138004C>T, g.+185219G>A, g.+191272A>C, and g.+265317T>A) were associated with the risk of obesity in three models (codominant, dominant, and recessive) (P=0.007-0.05). Haplotype 1 (CAC) and 3 (TAC) of block 3 and haplotype 2 (GGAAT) of block 10 were also strongly associated with the risk of obesity. In the control group, subjects that had homozygote for the major allele for both g.+185219G>A and g.+191272A>C showed lower high density lipoprotein-cholesterol (HDL-C) level compared to those possessing the minor allele, suggesting that the association between the homozygote for the major allele for both g.+185219G>A and g.+191272A>C and HDL-C is attributable to the increased risk of obesity. This study suggests that the PBX1 gene is a possible risk factor in overweight/obese patients.
RESUMEN
Oxidative stress is produced under diabetic conditions and involved in progression of pancreatic beta-cell dysfunction. Both an increase in reactive oxygen free radical species (ROS) and a decrease in the antioxidant defense mechanism lead to the increase in oxidative stress in diabetes. Electrolyzed reduced water (ERW) with ROS scavenging ability may have a potential effect on diabetic animals, a model for high oxidative stress. Therefore, the present study examined the possible anti-diabetic effect of ERW in genetically diabetic mouse strain C57BL/6J-db/db (db/db). ERW with ROS scavenging ability reduced the blood glucose concentration, increased blood insulin level, improved glucose tolerance and preserved beta-cell mass in db/db mice. The present data suggest that ERW may protects beta-cell damage and would be useful for antidiabetic agent.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Electrólisis , Hipoglucemiantes/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Agua , Animales , Glucemia/análisis , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Modelos Animales de Enfermedad , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Masculino , Ratones , Ratones Obesos , Oxidación-ReducciónRESUMEN
BACKGROUND: Vitiligo is a skin disorder affected by genetic, environmental, local and endocrine factors. Endothelin-1, which is expressed by keratinocytes, has paracrine effects on melanocytes, influencing their homeostasis, proliferation and pigmentation. It is thought to play a role in the skin response to 311-nm, narrow-band ultraviolet irradiation. OBJECTIVE: To investigate the association of endothelin-1 gene (EDN1) polymorphisms with vitiligo in a Korean population. METHODS: To evaluate the expression of endothelin-1 in cultured human keratinocytes after irradiation with narrow-band ultraviolet B (NBUVB), we performed RT-PCR and ELISA. In addition, we genotyped 312 vitiligo patients and 313 matched-healthy controls, and compared the genotype, allele and haplotype frequencies of EDN1 polymorphisms (intron 4 G/A, rs2071942 and exon 5 G/T, rs5370) between the two groups, using PCR-restriction fragment length polymorphism. The effects of sex, onset age, the presence of autoimmune diseases, family history and clinical type were analysed statistically. RESULTS: NBUVB induced the expression of endothelin-1 in cultured human keratinocytes. The genotype distributions and allele frequencies of EDN1 polymorphisms did not differ significantly between vitiligo patients and healthy controls. Moreover, the results were not related to sex, onset age, the presence of autoimmune diseases or family history. Interestingly, the haplotype frequencies of EDN1 polymorphisms differed significantly between vitiligo patients and healthy controls. When analysed according to clinical type, the haplotype frequencies in the focal and segmental clinical types differed significantly from healthy controls. CONCLUSION: This study suggests that EDN1 is related to the development of vitiligo in the Korean population.
Asunto(s)
Endotelina-1/genética , Queratinocitos/efectos de la radiación , Polimorfismo de Nucleótido Simple , Vitíligo/genética , Adolescente , Adulto , Estudios de Casos y Controles , Células Cultivadas , Endotelina-1/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Recién Nacido , Queratinocitos/metabolismo , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Piel/patología , Rayos Ultravioleta , Vitíligo/metabolismo , Vitíligo/patologíaRESUMEN
Vitiligo is an acquired pigmentary disorder characterized by well-circumscribed depigmented patches. Autoimmune, self-destruction, neural, and genetic theories have been proposed for the pathogenesis of vitiligo. Reactive oxygen species play an important role in the physiology of cell damage, and catalase is known to regulate oxidative stress. Reduced catalase enzyme activity and accumulation of excessive hydrogen peroxide were observed in vitiligo. To examine whether catalase gene polymorphisms are associated with vitiligo patients in Korean population, we investigated two CAT gene polymorphisms including (T/C) BstX I (A/T) Hinf I in 118 vitiligo patients and 200 healthy volunteers. The CAT gene genotype distribution and allele frequency were not significantly different between vitiligo patients and healthy controls. But, the haplotype of two polymorphisms was associated with vitiligo. This study suggests possible association between the CAT gene and the vitiligo susceptibility.