Retinoic acid as modulator of UVB-induced melanocyte differentiation. Involvement of the melanogenic enzymes expression

1994 ◽  
Vol 107 (4) ◽  
pp. 1095-1103
Author(s):  
C. Romero ◽  
E. Aberdam ◽  
C. Larnier ◽  
J.P. Ortonne
Keyword(s):  
Retinoic Acid ◽  
Sun Exposure ◽  
Transcriptional Level ◽  
Related Protein ◽  
Dopachrome Tautomerase ◽  
Normal Human ◽  
Cis And Trans ◽  
Vitro Effect ◽  
Tyrosinase Related Protein

Retinoic acid (RA) is a hormone-like agent involved in the control of cell differentiation. The most characteristic feature of melanocyte differentiation, melanogenesis, is stimulated by UV radiations. Excessive chronic sun exposure results in irregular skin hypermelanosis that can be partially corrected by topical RA. The basic mechanisms underlying this effect of RA are unknown. To determine whether RA can directly modulate excessive melanin synthesis, we analyzed the in vitro effect of cis- and trans-RA on UVB-induced melanogenesis in S91 mouse melanoma cells and in normal human melanocytes (NHM). In both cells types, the two RA isoforms significantly decreased the UVB-stimulated melanogenesis in term of tyrosinase activity and melanin neosynthesis. To correlate changes in melanogenesis with the expression of melanogenic enzymes, we determined the neosynthesis rate of tyrosinase, tyrosinase-related protein-1 (TRP-1/gp 75) and tyrosinase-related protein-2 (TRP-2/DOPAchrome tautomerase). Here we show that UVB-induced melanogenesis in NHM is related to an increased synthesis of tyrosinase and TRP-1 and to a dramatic decrease of TRP-2 expression. RA inhibition of UVB-induced melanogenesis acts at the post-transcriptional level leading to a decreased tyrosinase and TRP-1 synthesis. We also show that in NHM, inhibition of TRP-2 following UVB-treatment is significantly reversed by RA. This demonstrates a negative correlation between melanogenesis and TRP-2 expression.

scholarly journals Tara Tannin Regulates Pigmentation by Modulating Melanogenesis Enzymes and Melanosome Transport Proteins Expression

2020 ◽  
Vol 7 (01) ◽  
pp. e34-e44
Author(s):  
Myra O. Villareal ◽  
Thanyanan Chaochaiphat ◽  
Meriem Bejaoui ◽  
Kozo Sato ◽  
Hiroko Isoda
Keyword(s):  
Skin Color ◽  
Pigment Cell ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Transport Proteins ◽  
Related Protein ◽  
Promoting Effect ◽  
Dopachrome Tautomerase ◽  
Tyrosinase Related Protein

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.

scholarly journals Identification of L-Cysteinamide as a Potent Inhibitor of Tyrosinase-Mediated Dopachrome Formation and Eumelanin Synthesis

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1202
Author(s):  
Hyun Kyung Lee ◽  
Jae Won Ha ◽  
Yun Jeong Hwang ◽  
Yong Chool Boo
Keyword(s):  
Melanin Content ◽  
Thiol Compounds ◽  
Dopachrome Tautomerase ◽  
Protein Levels ◽  
Identify Amino Acid ◽  
Normal Human ◽  
Melanin Contents ◽  
Dual Mechanism ◽  
Tyrosinase Related Protein

The purpose of this study is to identify amino acid derivatives with potent anti-eumelanogenic activity. First, we compared the effects of twenty different amidated amino acids on tyrosinase (TYR)-mediated dopachrome formation in vitro and melanin content in dark-pigmented human melanoma MNT-1 cells. The results showed that only L-cysteinamide inhibited TYR-mediated dopachrome formation in vitro and reduced the melanin content of cells. Next, the antimelanogenic effect of L-cysteinamide was compared to those of other thiol compounds (L-cysteine, N-acetyl L-cysteine, glutathione, L-cysteine ethyl ester, N-acetyl L-cysteinamide, and cysteamine) and positive controls with known antimelanogenic effects (kojic acid and β-arbutin). The results showed the unique properties of L-cysteinamide, which effectively reduces melanin content without causing cytotoxicity. L-Cysteinamide did not affect the mRNA and protein levels of TYR, tyrosinase-related protein 1, and dopachrome tautomerase in MNT-1 cells. L-Cysteinamide exhibited similar properties in normal human epidermal melanocytes (HEMs). Experiments using mushroom TYR suggest that L-cysteinamide at certain concentrations can inhibit eumelanin synthesis through a dual mechanism by inhibiting TYR-catalyzed dopaquinone synthesis and by diverting the synthesized dopaquinone to the formation of DOPA-cysteinamide conjugates rather than dopachrome. Finally, L-cysteinamide was shown to increase pheomelanin content while decreasing eumelanin and total melanin contents in MNT-1 cells. This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and HEMs, and will be useful in controlling skin hyperpigmentation.

scholarly journals Depigmentation Activity of Secang (Caesalpinia Sappan L.) Extract Through Tyrosinase, Tyrosinase Related Protein-1 and Dopachrome Tautomerase Inhibition

2019 ◽  
Vol 12 (2) ◽  
pp. 799-808 ◽  
Author(s):  
Ni Putu Linda Laksmiani ◽  
I. Putu Wiratama Nugraha
Keyword(s):  
Ascorbic Acid ◽  
Kojic Acid ◽  
Ethanolic Extract ◽  
Related Protein ◽  
Caesalpinia Sappan ◽  
Dopachrome Tautomerase ◽  
Inhibitory Ability ◽  
Tyrosinase Enzyme ◽  
Tyrosinase Related Protein

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.

scholarly journals Isolation of cDNA clones for genes exhibiting reduced expression after differentiation of murine teratocarcinoma stem cells.

1984 ◽  
Vol 4 (10) ◽  
pp. 2142-2150 ◽  
Author(s):  
R A Levine ◽  
G J LaRosa ◽  
L J Gudas
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Cyclic Amp ◽  
Cdna Library ◽  
In Vitro Transcription ◽  
In Vitro Translation ◽  
Transcriptional Level ◽  
Cdna Clones ◽  
Dibutyryl Cyclic Amp

In the absence of retinoic acid, PSA-G teratocarcinoma stem cells spontaneously differentiate at a moderate frequency into fibroblast-like cells. In the presence of retinoic acid and dibutyryl cyclic AMP, PSA-G stem cells differentiate into parietal endoderm cells. We prepared a cDNA library from undifferentiated PSA-G teratocarcinoma stem cells; this cDNA library was then screened for gene sequences which exhibit a reduction in expression during the differentiation of these stem cells. From ca. 1,000 clones screened, eight independent sequences were isolated. The level of expression of these cloned genes decreases by 3.0-fold to more than 10-fold after differentiation of PSA-G cells into fibroblast-like cells. After treatment of either PSA-G or F9 teratocarcinoma cells with retinoic acid and dibutyryl cyclic AMP for 72 h, the expression of seven genes is inhibited by two- to fourfold. This decrease of clone-specific transcripts can be detected within 12 h after the addition of retinoic acid. Hybridization-selection and in vitro translation experiments identified the proteins encoded by three of the cloned genes: pST 6-23 codes for a 89,000-dalton protein, pST 7-105 codes for a 41,000-dalton protein, and pST 9-31 codes for a 34,000-dalton protein. The 89,000-dalton protein encoded by pST 6-23 is a heat shock protein. In vitro transcription experiments demonstrate that the retinoic acid-mediated decrease in pST 6-135- and pST 1-68-specific RNA occurs at the transcriptional level and that dibutyryl cyclic AMP acts posttranscriptionally to further depress the levels of these RNAs.

scholarly journals Physiological and Receptor-selective Retinoids Modulate Interferon γ Signaling by Increasing the Expression, Nuclear Localization, and Functional Activity of Interferon Regulatory Factor-1

2005 ◽  
Vol 280 (43) ◽  
pp. 36228-36236 ◽  
Author(s):  
Xin M. Luo ◽  
A. Catharine Ross
Keyword(s):  
Retinoic Acid ◽  
Nuclear Localization ◽  
Target Genes ◽  
Interferon Γ ◽  
Epithelial Cell Line ◽  
Transcriptional Level ◽  
Signal Transducer ◽  
Regulatory Factor

Synergistic actions between all-trans-retinoic acid (atRA) and interferon γ (IFNγ) on modulation of cellular functions have been reported both in vitro and in vivo. However, the mechanism of atRA-mediated regulation of IFNγ signaling is poorly understood. In this study, we have used the human lung epithelial cell line A549 to examine the effect of atRA on IFNγ-induced expression of IFN regulatory factor-1 (IRF-1), an important transcription factor involved in cell growth and apoptosis, differentiation, and antiviral and antibacterial immune responses. At least 4 h of pretreatment with atRA followed by suboptimal concentrations of IFNγ induced a faster, higher, and more stable expression of IRF-1 than IFNγ alone. Actinomycin D completely blocked the induction of IRF-1 by the combination, suggesting regulation at the transcriptional level. Further, we found that activation of signal transducer and activator of transcription-1 was induced more dramatically by atRA and IFNγ than by IFNγ alone. Expression of IFNγ receptor-1 on the cell surface was also increased upon atRA pretreatment. Experiments using receptor-selective retinoids revealed that ligands for retinoic acid receptor-α (RARα), including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels of IFNγ receptor-1, activated signal transducer and activator of transcription-1, and IRF-1 and that an RARα antagonist was able to inhibit the effects of atRA and Am580. In addition, atRA pretreatment affected the transcriptional functions of IFNγ-induced IRF-1, increasing its nuclear localization and DNA binding activity as well as the transcript levels of IRF-1 target genes. These results suggest that atRA, an RARα ligand, regulates IFNγ-induced IRF-1 by affecting multiple components of the IFNγ signaling pathway, from the plasma membrane to the nuclear transcription factors.

Expression of Tyrosinase-related Protein 2/DOPAchrome Tautomerase in the Retinoblastoma

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

scholarly journals Melanocytes and Pigmentation Are Affected in Dopachrome Tautomerase Knockout Mice

2004 ◽  
Vol 24 (8) ◽  
pp. 3396-3403 ◽  
Author(s):  
Laurence Guyonneau ◽  
Fabien Murisier ◽  
Anita Rossier ◽  
Alexandre Moulin ◽  
Friedrich Beermann
Keyword(s):  
Knockout Mice ◽  
Null Allele ◽  
Coat Color ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Related Protein ◽  
Melanin Content ◽  
Dopachrome Tautomerase ◽  
Exon 1 ◽  
Tyrosinase Related Protein

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.

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