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 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.

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 Anti-Melanogenic Effects of Hydroxyectoine via MITF Inhibition by JNK, p38, and AKT Pathways in B16F10 Melanoma Cells

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1985852 ◽  
Author(s):  
You C. Chung ◽  
Min-Jin Kim ◽  
Eun Y. Kang ◽  
Yun B. Kim ◽  
Bong S. Kim ◽  
...  
Keyword(s):  
Skin Color ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Related Protein ◽  
B16f10 Melanoma ◽  
Melanin Production ◽  
B16f10 Cells ◽  
Dose Dependent ◽  
Tyrosinase Related Protein

Melanin plays a role in determining human skin color of a person, and a large amount of melanin makes the skin color look darkened. The proper amount of melanin formation protects our skin from UV radiation, but excessive melanin production causes hyperpigmentation and leads to freckles, melasma, and lentigo. In this study, we investigated the inhibitory effect of hydroxyectoine on melanogenesis and its mechanism in B16F10 cells. Melanin content and cellular tyrosinase activity were determined. The expression of microphthalmia-associated transcription factor (MITF), and the activities of tyrosinase and other melanogenesis-related enzymes, such as tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2, were also examined. Hydroxyectoine treatment significantly inhibited melanin production and intracellular tyrosinase activity in a dose-dependent manner. Western blot analysis showed that hydroxyectoine also reduced the expressions of tyrosinase and TRP-1. In addition, hydroxyectoine significantly reduced the expression of MITF, a major regulator of melanin production, and inhibited the phosphorylation of p38, c-Jun N-terminal kinase, and activated the protein kinase B. The results demonstrated that hydroxyectoine inhibits the expression of MITF through the inhibition or activation of melanin-related signaling pathways and downregulates melanogenesis by inhibiting melanogenic enzyme expression and tyrosinase activity. Hydroxyectoine has potential value in functional cosmetics applications, such as whitening.

scholarly journals Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Yiwei Wang ◽  
Minghui Zhao ◽  
Sijia He ◽  
Yuntao Luo ◽  
Yucui Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Stimulation ◽  
Underlying Mechanism ◽  
Promoting Effect ◽  
Clinical Prognosis ◽  
Associated Proteins ◽  
Radiation Induced ◽  
Colorectal Cancer Patients

Abstract Background Tumor cell repopulation after radiotherapy is a major cause for the tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of tumor repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process. Methods Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo tumor repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal tumor specimens to verify the relationship with clinical outcome. Results Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated tumor cells on living tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced tumor repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients. Conclusions Necroptosis associated tumor repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of tumor radioresistance and repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking tumor repopulation to enhance the efficacy of colorectal cancer radiotherapy.

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

Investigation of the anti-diabetic nephropathy activity of puerarin

2020 ◽  
Vol 10 (11) ◽  
pp. 1846-1853
Author(s):  
Wen-Feng Zhang ◽  
Yan Yang ◽  
Xin Li ◽  
Bo Yang ◽  
Pei-Yu He ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Collagen Type Iv ◽  
Therapeutic Effects ◽  
Type Iv ◽  
Enzymelinked Immunosorbent Assay ◽  
Hematoxylin And Eosin

Puerarin has potential therapeutic effects on diabetic nephropathy (DN), but the effectiveness as a treatment for DN and the underlying mechanism remain to be elucidated. The DN-like model induced by high glucose in vitro and the DN model induced by streptozotocin in vivo were used to observe the effect of puerarin. The results showed that puerarin can enhance the activity of HBZY-1 cells and reduce apoptosis. in vivo enzymelinked immunosorbent assay and biochemical assay showed that puerarin can improve DN symptoms. Using hematoxylin and eosin staining to stain kidney tissues confirmed that puerarin has a protective effect on DN. Furthermore, puerarin can reduce the content of collagen type IV, laminin LN, tumor necrosis factor, p38, CREB, Fos, Jun, and MMP9 in HBZY-1 cells and DN rats. In conclusion, puerarin can effectively prevent apoptosis in vitro and improve DN-like symptoms by inhibiting the p38/MAPK signaling pathway in vivo. Therefore, puerarin has the potential to treat DN.

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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