scholarly journals UP256 Inhibits Hyperpigmentation by Tyrosinase Expression/Dendrite Formation via Rho-Dependent Signaling and by Primary Cilium Formation in Melanocytes

2020 ◽  
Vol 21 (15) ◽  
pp. 5341
Author(s):  
Min Cheol Kang ◽  
Jae-Wook Lee ◽  
Taek Hwan Lee ◽  
Lalita Subedi ◽  
Hussain M. Wahedi ◽  
...  
Keyword(s):  
Primary Cilium ◽  
Acne Vulgaris ◽  
Signaling Proteins ◽  
Melanin Synthesis ◽  
Glutathione S Transferase ◽  
Cytotoxic Effects ◽  
Dendrite Formation ◽  
Cilium Formation ◽  
Normal Human ◽  
Melanin Contents

Skin hyperpigmentation is generally characterized by increased synthesis and deposition of melanin in the skin. UP256, containing bakuchiol, is a well-known medication for acne vulgaris. Acne sometimes leaves dark spots on the skin, and we hypothesized that UP256 may be effective against hyperpigmentation-associated diseases. UP256 was treated for anti-melanogenesis and melanocyte dendrite formation in cultured normal human epidermal melanocytes as well as in the reconstituted skin and zebrafish models. Western blot analysis and glutathione S-transferase (GST)-pull down assays were used to evaluate the expression and interaction of enzymes related in melanin synthesis and transportation. The cellular tyrosinase activity and melanin content assay revealed that UP256 decreased melanin synthesis by regulating the expression of proteins related on melanogenesis including tyrosinase, TRP-1 and -2, and SOX9. UP256 also decreased dendrite formation in melanocytes via regulating the Rac/Cdc42/α-PAK signaling proteins, without cytotoxic effects. UP256 also inhibited ciliogenesis-dependent melanogenesis in normal human epidermal melanocytes. Furthermore, UP256 suppressed melanin contents in the zebrafish and the 3D human skin tissue model. All things taken together, UP256 inhibits melanin synthesis, dendrite formation, and primary cilium formation leading to the inhibition of melanogenesis.

scholarly journals Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

2021 ◽  
Vol 22 (7) ◽  
pp. 3755
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  
Keyword(s):  
Uv Radiation ◽  
Therapeutic Potential ◽  
Melanin Synthesis ◽  
Uvb Radiation ◽  
Biochemical Basis ◽  
Skin Hyperpigmentation ◽  
Human Melanocytes ◽  
Anti Cancer ◽  
Normal Human

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

scholarly journals Antioxidants, Phytochemicals, and Cytotoxicity Studies onPhaleria macrocarpa(Scheff.) Boerl Seeds

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Ma Ma Lay ◽  
Saiful Anuar Karsani ◽  
Behrooz Banisalam ◽  
Sadegh Mohajer ◽  
Sri Nurestri Abd Malek
Keyword(s):  
Human Cancer ◽  
Cytotoxic Effects ◽  
Nutritional Values ◽  
Water Fraction ◽  
Human Cancer Cells ◽  
Fiber Protein ◽  
Cytotoxicity Studies ◽  
Normal Human ◽  
Lung Cell Line ◽  
Mcf 7

In recent years, the utilization of certain medicinal plants as therapeutic agents has drastically increased.Phaleria macrocarpa(Scheff.) Boerl is frequently used in traditional medicine. The present investigation was undertaken with the purpose of developing pharmacopoeial standards for this species. Nutritional values such as ash, fiber, protein, fat, and carbohydrate contents were investigated, and phytochemical screenings with different reagents showed the presence of flavonoids, glycosides, saponin glycosides, phenolic compounds, steroids, tannins, and terpenoids. Our results also revealed that the water fraction had the highest antioxidant activity compared to the methanol extract and other fractions. The methanol and the fractionated extracts (hexane, chloroform, ethyl acetate, and water) ofP. macrocarpaseeds were also investigated for their cytotoxic effects on selected human cancer cells lines (MCF-7, HT-29, MDA-MB231, Ca Ski, and SKOV-3) and a normal human fibroblast lung cell line (MRC-5). Information from this study can be applied for future pharmacological and therapeutic evaluations of the species, and may assist in the standardization for quality, purity, and sample identification. To the best of our knowledge, this is the first report on the phytochemical screening and cytotoxic effect of the crude and fractionated extracts ofP. macrocarpaseeds on selected cells lines.

scholarly journals Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

2020 ◽  
Author(s):  
xiaoli li ◽  
dingwei zhang ◽  
jiahui ding ◽  
li li ◽  
zhenghui wang
Keyword(s):  
Nonsense Mutation ◽  
Polypeptide Chain ◽  
Stop Codon ◽  
Skin Lesions ◽  
Signaling Proteins ◽  
Missense Mutations ◽  
Functional Region ◽  
Bullous Dermatosis ◽  
Normal Human ◽  
Regulatory Effects

Abstract Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients. Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

scholarly journals Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

2020 ◽  
Author(s):  
xiaoli li ◽  
dingwei zhang ◽  
jiahui ding ◽  
li li ◽  
zhenghui wang
Keyword(s):  
Nonsense Mutation ◽  
Polypeptide Chain ◽  
Stop Codon ◽  
Skin Lesions ◽  
Signaling Proteins ◽  
Missense Mutations ◽  
Functional Region ◽  
Bullous Dermatosis ◽  
Normal Human ◽  
Regulatory Effects

Abstract Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients. Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

scholarly journals Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease

2020 ◽  
Author(s):  
xiaoli li ◽  
dingwei zhang ◽  
jiahui ding ◽  
li li ◽  
zhenghui wang
Keyword(s):  
Nonsense Mutation ◽  
Polypeptide Chain ◽  
Stop Codon ◽  
Skin Lesions ◽  
Signaling Proteins ◽  
Missense Mutations ◽  
Functional Region ◽  
Bullous Dermatosis ◽  
Normal Human ◽  
Regulatory Effects

Abstract Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients. Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

scholarly journals A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Leticia Labat-de-Hoz ◽  
Armando Rubio-Ramos ◽  
Javier Casares-Arias ◽  
Miguel Bernabé-Rubio ◽  
Isabel Correas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Control Cell ◽  
Future Research ◽  
Alternative Route ◽  
Ciliary Membrane ◽  
Cilium Formation ◽  
Membrane Compartmentalization

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

Placental extracts regulate melanin synthesis in normal human melanocytes with alterations of mitochondrial respiration

2019 ◽  
Vol 28 ◽  
pp. 50-54 ◽  
Author(s):  
Satoshi Yoshimoto ◽  
Yoshiaki Ohagi ◽  
Moemi Yoshida ◽  
Hiroki Yanagi ◽  
Sawako Hibino ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Melanin Synthesis ◽  
Human Melanocytes ◽  
Normal Human

Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes

2020 ◽  
Vol 107 (6) ◽  
pp. 625-635
Author(s):  
Dong Ding ◽  
Xiao Yang ◽  
Hui-qin Luan ◽  
Xin-tong Wu ◽  
Cai He ◽  
...  
Keyword(s):  
Primary Cilium ◽  
Cilium Formation ◽  
Pharmacological Regulation

The Cytotoxicity of Continuous Ambulatory Peritoneal Dialysis Solutions with Different Bicarbonate/Lactate Ratios

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 116-118 ◽  
Author(s):  
Hans Thalsgård Schambye ◽  
Fritz Bangsgaard Pedersen ◽  
Hanne Knoldsborg Christensen ◽  
Henrik Berthelsen ◽  
Palle Wang
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Culture Medium ◽  
Lactate Concentration ◽  
Cellular Function ◽  
Bicarbonate Concentration ◽  
Cytotoxic Effects ◽  
Migratory Capacity ◽  
Normal Human ◽  
Dialysis Solutions

Five different bicarbonate-based continuous ambulatory peritoneal dialysis (CAPD) solutions (pH: 7.0-7.4; bicarbonate: 10-27 mM; lactate: 20.8–0.7 mM) were produced in order to examine the cytotoxic effects of the different compositions. The migratory capacity of normal human polymorphonuclear (PMN) granulocytes after exposure to the solutions was used as a cytotoxicity assay. All the tested solutions reduced cellular function compared to a standard cell culture medium, but considerable differences between the solutions were observed. The optimal Conditions for the PMN migration were at a pH of 7.0 and at bicarbonate and lactate concentrations of 20 mM and 12.5 mM, respectively. Bicarbonate concentrations of more than 25 mM were associated with reduced cellular function as were lactate concentrations of more than 15 mM. The most advantageous CAPD solution regarding cytotoxicity towards normal human PMN's is a combination of a lactate and bicarbonate-based solution, which has a bicarbonate concentration of approximately 20 mM, a lactate concentration of 12.5 mM, and a pH of approximately 7.2.

Sign in / Sign up

Export Citation Format

Share Document