• Korean Journal of Plant Resources
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• v.27 no.3
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• pp.209-214
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• 2014

In this study, we investigated whether A. distichum decreases the production of inflammatory mediators through downregulation of the NF-${\kappa}B$ and ERK pathway. Our data indicated that A. distichum leaf inhibits the overexpression of iNOS in protein and mRNA levels, and subsequently blocked LPS-mediated NO overproduction in RAW264.7 cells. A. distichum leaf inhibited $I{\kappa}B-{\alpha}$ degradation and p65 nuclear translocation, and subsequently suppressed transcriptional activity of NF-${\kappa}B$ in LPS-stimulated RAW264.7 cells. In addition, A. distichum leaf suppressed LPS-induced ERK1/2 activation by decreasing phosphorylation of ERK1/2. These findings suggest that A. distichum leaf shows anti-inflammatory activities through suppressing ERK-mediated NF-${\kappa}B$ activation in mouse macrophage.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.29-34
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• 2015

Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the class Phaeophyceae, has been widely studied for its possible health benefits. However, the potential of fucoidan as a possible treatment for hyperpigmentation is not fully understood. This study investigated the effects of fucoidan on melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan significantly decreased melanin content. While fucoidan treatment decreased tyrosinase activity, it did not do so directly. Western blot analysis indicated that fucoidan downregulated microphthalmia-associated transcription factor and reduced tyrosinase protein expression. Further investigation showed that fucoidan activated the extracellular signal-regulated kinase (ERK) pathway, suggesting a possible mechanism for the inhibition of melanin synthesis. Treatment with PD98059, a specific ERK inhibitor, resulted in the recovery of melanin production. Taken together, these findings suggest that fucoidan inhibits melanogenesis via ERK phosphorylation.

• Korean Journal of Plant Resources
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• v.35 no.6
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• pp.704-712
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• 2022

Research on whitening materials using natural alternatives is actively being conducted. The aim of this study was to investigate the in vitro inhibitory effects of Ranunculus chinensis Bunge (RCB) on melanogenesis and associated enzymes, such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 in B16F10 murine melanoma cells. We found that RCB extract significantly attenuated melanin synthesis and reduced the activity of intracellular tyrosinase, a rate-limiting melanogenic enzyme. Western blot analysis showed that RCB extract decreased the protein expression of tyrosinase and TRP-1. In addition, it significantly decreased the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis. Extracellular signal-regulated kinase (ERK) activation has been reported to be involved in the inhibition of melanogenesis. Thus, we investigated whether the hypopigmentary effects of RCB extract were related to the activation of ERK. RCB extract induced ERK phosphorylation in a dose-dependent manner. Furthermore, it markedly inhibited body pigmentation in a zebrafish model. Our results suggest that RCB extract inhibits melanogenesis by activating ERK pathway-mediated suppression of MITF and its downstream target genes, including tyrosinase. Therefore, RCB extract can be used as a whitening agent in the development of functional cosmetics.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.271.3-272
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• 2002

This study shows that sphingosine-1-phosphate (SPP) significantly inhibits melanin synthesis in a concentration-dependent manner, and that the activity of tyrosinase was also reduced in SPP-treated cells. In contrast. a specific extracellular signal-regulated protein kinase (ERK) pathway inhibitor, PD98059 increased tyrosinase activity and melanin production, and PD98059 restored the reduced tyrosinase activity and pigmentation induced by SPP. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.90.1-90.1
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• 2003

This study shows that sphingosine-1-phosphate (S1P) significantly inhibits melanin synthesis in a concentration-dependent manner, and that the activity of tyrosinase was also reduced in S1P-treated cells. In contrast, a specific extracellular signal-regulated protein kinase (ERK) pathway inhibitor, PD98059 increased tyrosinase activity and melanin production, and PD98059 restored the reduced tyrosinase activity and pigmentation induced by SIP. We also found that S1P induces the sustained activation of ERK and the subsequent degradation of microphthalmia-associated transcription factor (MITF), which plays a key role in melanogenesis. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.389-395
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• 2011

Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or $2.0{\mu}g/side$), or U0126 (0.1 or $1.0{\mu}g/side$), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 ($2.0{\mu}g/side$) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.

• Animal cells and systems
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• v.8 no.1
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• pp.27-32
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• 2004

Endothellial cells are subjected to hemodynamic shear stress, the dragging force generated by blood flow. Shear stress regulates endothelial cell shape, structure, and function, including gene expression. Since endothelial cells must be anchored to their extracellular matrices(ECM) for their survival and growth, we hypothesized that ECMs are crucial for shear-dependent activation of extracellular signalactivated regulated kinase(ERK) that is important for cell proliferation. Shear stress-dependent activation of ERK was observed in cells plated on two different matrices, fibronectin and vitronectin(the two most physiologically relevant ECM in endothelial cells). We then treated bovine aortic endothelial cells(BAECs) with Arg-Gly-Asp(RGD) peptides that block the functional activation of integrin binding to fibronectin and vitronectin, and a nonfunctional peptide as a control. Treatment of cells with the RGD peptides, but not the control peptide, significantly inhibited ERK activity in a concentration-dependent manner. This supports the idea that integrin adhesion to the ligands, fibronectin and vitronectin, mediates shear stress-dependent activation of ERK. Subsequently, whereas antagonists of vitronectin(LM 609, an antibody for integrin ${\alpha}_{\gamma}$/${\beta}_3$ and XT 199, an antagonist specific for integrin ${\alpha}_{\gamma}$/${\beta}_3$) did not have any effect on shear-dependent activation of ERK, antagonists of fibronectin(a neutralizing antibody for integrin ${\alpha}_5$/${\beta}_1$or ${\alpha}_4$${\beta}_1$ and SM256) had an inhibitory effect. These results clearly demonstrate that mechanoactivation of ERK requires anchoring of endothelial cells to fibronectin through integrins.

• Molecules and Cells
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• v.39 no.3
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• pp.266-279
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• 2016

The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) ${\alpha}$ and $PKC{\beta}1$ exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. $PKC{\alpha}$ accompanied pErk1/2 to the nucleus after freeing it from $PEA-15pS^{104}$ via $PKC{\beta}1$ and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of $PKC{\alpha}$ were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated $PKC{\alpha}$ expression and increased epidermal and hair follicle cell proliferation. Thus, $PKC{\alpha}$ downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear $PKC{\alpha}$ degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of $PKC{\alpha}$ expression following TPA treatment reduces pErk1/2-activated SP1 biding to the $p21^{WAF1}$ gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.

• The Korean Journal of Food And Nutrition
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• v.28 no.4
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• pp.579-585
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• 2015

Rutin is a well-known flavonoid found in buckwheat. Recent studies have demonstrated that the biological actions of rutin include anti-inflammatory and anti-cancer effects, but the underlying molecular mechanisms of these actions are not yet fully understood. Neoplastic cell transformation is considered a major event that contributes to carcinogenesis, and the present study aimed to determine whether rutin would exert anti-tumor effects via the results suggest that rutin exerted a potent inhibitory influence on the molecular activity of the MEK/ERK and MKK4/JNK pathways and strongly attenuated EGF-induced neoplastic cell transformation. These findings provide insight into the biological actions of rutin and the molecular basis for the development of new chemoprotective agents.

• Journal of Life Science
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• v.24 no.1
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• pp.8-13
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• 2014

The moringa (Moringa oleifera Lam.) plant is used as food and as an anti-allergic agent. In this study, we studied the inhibitory effect of moringa root extract on the expression of PMA-induced matrix metalloproteinase-9 (MMP-9), which is the main factor implicated in the invasion and metastasis of cancer cells in MCF-7 cells. At first, various moringa extracts were examined in the MCF-7 cells. Both moringa root extract and leaf extracts inhibited PMA-induced MMP-9 activity, but the root extract suppressed PMA-induced MMP-9 activity to a greater extent than the leaf extract. The moringa root extract also inhibited PMA-induced MMP-9 protein expression and cell invasion. According to RT-PCR, the treatment of the MCF-7 cells with moringa root extract decreased levels of PMA-induced MMP-9 mRNA expression, but not the expression of TIMP-1 and -2, indicating that moringa root extract prevents the transcription of MMP-9 in response to PMA. In addition, moringa root extract specifically suppressed the phosphorylation of ERK/JNK, but not p38. We suggest that moringa root extract abolishes MMP-9 activity/expression through ERK/JNK. In conclusion, moringa root extract suppressed PMA-induced MMP-9 activity/expression by inhibiting the phosphorylation of ERK/JNK in MCF-7 cells. These results indicate that moringa root extract may be a potential antimetastatic and anti-invasive agent. Future clinical research is needed on the anticancer properties of moringa root extract.