scholarly journals Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression.

1994 ◽  
Vol 269 (43) ◽  
pp. 27080-27087
Author(s):  
K Yokoyama ◽  
K Yasumoto ◽  
H Suzuki ◽  
S Shibahara
2020 ◽  
Vol 7 (01) ◽  
pp. e34-e44
Author(s):  
Myra O. Villareal ◽  
Thanyanan Chaochaiphat ◽  
Meriem Bejaoui ◽  
Kozo Sato ◽  
Hiroko Isoda

AbstractThe skin color is imparted by the pigment melanin produced in the melanosomes of melanocytes, through the catalytic action of melanogenesis enzymes tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase. Disruptions in the melanogenesis process may result to hypopigmentation, as observed in cutaneous postinflammatory conditions. Here, the bioactivity of tara tannin, specifically on melanogenesis, was evaluated in vitro using human epidermal melanocytes (HEM) and B16F10 murine melanoma cells in order to determine the possibility that it may be used as a treatment against hypopigmentation. The melanin content of tara tannin-treated B16F10 cells and the expression level of melanogenesis enzymes and melanosome transport proteins were determined. To elucidate the underlying mechanism of tara tannin’s effect on melanogenesis, DNA microarray analysis was performed. Tara tannin significantly increased melanogenesis in both murine and human pigment cell models by upregulating melanogenesis-associated enzymes’ (tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase) protein and mRNA expression levels, as well as the melanosome transport proteins (myosin Va and RAB27A) expression, both attributed to increased microphthalmia-associated transcription factor (MITF) expression. Global gene expression analysis results revealed the modulation of genes (p≤0.05; fold-change ≥2.0 and ≤−2.0) that are under the transcriptional regulation of MITF and genes relevant for MAPK signaling, metabolic pathways, and cell cycle. Tara tannin has a significant effective melanogenesis-promoting effect, making it a potential therapeutic agent against hypopigmentation disorders. This is the first report on the melanogenesis regulatory effect of tara tannin in vitro.


2001 ◽  
Vol 72 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Tetsuo Udono ◽  
Kazuhiro Takahashi ◽  
Ken-ichi Yasumoto ◽  
Miki Yoshizawa ◽  
Kazuhisa Takeda ◽  
...  

2004 ◽  
Vol 24 (8) ◽  
pp. 3396-3403 ◽  
Author(s):  
Laurence Guyonneau ◽  
Fabien Murisier ◽  
Anita Rossier ◽  
Alexandre Moulin ◽  
Friedrich Beermann

ABSTRACT The tyrosinase family comprises three members, tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and dopachrome tautomerase (Dct). Null mutations and deletions at the Tyr and Tyrp1 loci are known and phenotypically affect coat color due to the absence of enzyme or intracellular mislocalization. At the Dct locus, three mutations are known that lead to pigmentation phenotype. However, these mutations are not null mutations, and we therefore set out to generate a null allele at the Dct gene locus by removing exon 1 of the mouse Dct gene. Mice deficient in Dct [Dcttm1(Cre)Bee ] lack Dct mRNA and dopachrome tautomerase protein. They are viable and do not show any abnormalities in Dct-expressing sites such as skin, retinal pigment epithelium, or brain. However, the mice show a diluted coat color phenotype, which is due to reduced melanin content in hair. Primary melanocytes from Dct knockout mice are viable in culture and show a normal distribution of tyrosinase and tyrosinase-related protein 1. In comparison to the knockout, the slaty mutation (Dctslt /Dctslt ) has less melanin and affects growth of primary melanocytes severely. In summary, we have generated a knockout of the Dct gene in mice with effects restricted to pigment production and coat color.


2019 ◽  
Vol 12 (2) ◽  
pp. 799-808 ◽  
Author(s):  
Ni Putu Linda Laksmiani ◽  
I. Putu Wiratama Nugraha

Excessive exposure of UV light increase melanin synthesis and cause hyperpigmentation of the skin. The pharmacological activity of secang (Caesalpinia sappan L.) with the main compound, brazilien and brazilin as antioxidants that have potency as free radicals scavenger and directly inhibit tyrosinase activity in the process of melanogenesis. This study aims to determine the inhibitory ability of secang ethanolic extract on tyrosinase enzymes in vitro and evaluate the affinity of brazilein and brazilin as skin depigmentation agents against melanogenesis target protein in silico using molecular docking. In vitro testing using tyrosinase inhibitor assay with L-DOPA as its substrate and calculated the percentage inhibition value and IC50. The IC50 of the extract than compared with the positive control, namely kojic acid and ascorbic acid. Insilico research was carried out using autodock 4.2 program by evaluating the binding energy between the active compound of brazilein and brazilin with melanogenesis protein. Inhibition of the tyrosinase enzyme is showed through the IC50 value from ethanolic extract, kojic acid and ascorbic acid respectively 104 μg/ mL, 44 μg/mL and 37 μg/mL. Binding energy of the molecular docking process between brazilein, brazilin, kojic acid and ascorbic acid with the target protein of melanogenesis enzymes (tyrosinase, tyrosinase related protein 1, and D-Dopachrome tauomerase) are -8.37; -6.56; -5.03; -5.35 kcal/mol in tyrosinase, -7.75; -6.40; -5.32; -5.8 kcal/mol in tyrosinase related proteins 1 and -9.93; -8.26; -5.8; -6.52 kcal/mol in D-Dopachrome tautomerase. Secang ethanolic extract could be developed into a skin lightening agent or depigmentation agent through inhibition of 3 target proteins that induce melanogenesis. Although invitro results show the inhibitory ability of the tyrosinase enzyme is lower than kojic acid and ascorbic acid but in silico, it is seen that brazilein and brazilin in secang ethanolic extract have a stronger affinity compared to kojic acid and ascorbic acid. For this reason, it is necessary to purify the extract into a fraction so that it can get more active ingredients of brazilein and brazilin, and in vitro testing for inhibition of the tyrosinase related protein 1 enzyme, and D-Dopachrome tautomerase.


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