• International journal of thyroidology
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• v.11 no.2
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• pp.152-159
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• 2018

Background and Objectives: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). Materials and Methods: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. Results: The PTCs with the $BRAF^{V600E}$ mutation and the coexistence of $BRAF^{V600E}$ and TERT promoter mutations showed significantly lower expression of NIS (p<0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p<0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p<0.001) and negative correlations with expressions of genes involved in ERK signaling (r=-0.164, p<0.001) and GLUT-1 gene (r=-0.204, p<0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. Conclusion: The NIS expression was reduced by the $BRAF^{V600E}$ mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.1
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• pp.62-68
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• 2020

Cisplatin (CDDP) is a chemotherapy agent used for patients with ovarian cancers. CDDP activates multiple signaling pathways, which causes various cellular reactions according to the type of cancer cells. Therefore, it is difficult to clearly conclude its signaling pathways. The purpose of this study is to determine the role of the signal protein of Akt/ERK1/2 and MAPK by CDDP-induced apoptosis in ovarian cancer cells (SKOV3). As a result, the number of apoptosis increased according to the TUNEL assay, and flow cytometric analysis confirmed that the percentage of sub-G1 early apoptosis was 8.73% higher than the control. The PARP and caspase-3 activity that appeared in the process of apoptosis was increased and the Bcl-2 expression was decreased. It was verified that the Akt and ERK1/2 activity was decreased, and p38 and JNK activity increased in a time dependent fashion. In conclusion, these results demonstrate that cisplatin inhibits the proliferation of ovarian cancer cells by inhibiting Akt activity and induces apoptosis by modulating the MAPK signaling pathway. However, a decrease in the ERK1/2 activity by CDDP was the opposite result to the result shown from the HeLa cells. For this reason, further research on signaling pathways is necessary. These results are expected to be useful for ovarian cancer treatment strategies targeting the MAPK pathway.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.39 no.2
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• pp.159-166
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• 2013

In order to develop new skin whitening agents, we prepared the EtOAc layer (AJE) after enzyme treatment of 75% EtOH extract of the Alnus Japonica Steud. We measured their tyrosinase inhibitory activity in vitro and melanin synthesis inhibitory activity in B16-F1 melanoma cells. They did not show inhibitory activity against mushroom tyrosinase but showed melanin synthesis inhibitory activity in a dose-dependent manner. In a melanin synthesis inhibition assay, AJE suppressed melanin production up to 52% at a concentration of $40{\mu}g/mL$. To elucidate the mechanism of the inhibitory effects of AJE on melanogenesis, we measured expression of melanogenesis-related proteins by the western blot assay. As a result, AJE suppressed the expression of tyrosinase related protein 1 (TRP-1) and microphthalmia associated transcription factor (MITF). Moreover, AJE increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). These results conclude that ERK activation by AJE reduces melanin synthesis via MITF downregulation and is subsequent to the inhibition of TRP-1 expression. Therefore, we suggest that AJE could be used as active ingredients for skin whitening.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.2
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• pp.1-12
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• 2015

Objective : The goal of this study is to identify the effects of extract ofGentianae sino-ornata(GSO) on the anti-oxidative activity of skin.For this purpose, several functions of GSO were analyzed in terms of skin-lightening activity and wrinkle improvement. Methods : Cell viability was measured by neutral red (NR) assay, and GSO showed highly efficacy in DPPH radical scavenging activity. The level of tyrosinase and matrix metalloproteinase-1 (MMP-1) in media was analyzed by ELISA kit, and the expressions of p-JNK and p-ERK was measured by Western blot. To elucidate inhibitory effects of GSO on melanin synthesis, I determined the tyrosinase activity and melanin production in B16F10 cells. Results : MMP-1 production in UVB-stimulated HDF cells was inhibited by GSO treatments, and also GSO inhibited protein expression levels of p-JNK and p-ERK. GSO significantly reduced tyrosinase activity and melanin synthesis in B16F10 cells. Conclusions : From these results, GSO appears to be effective on skin elasticity increase, wrinkle improvement, whitening as anti-aging activity.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.418-424
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• 2012

Repeated stress induces corticosterone release. However, it is not clear that stress results in further elevation of corticosterone levels, and the roles of released corticosterone to aggravate stress-related symptoms are also not clear. This study investigated whether neuronal modulation was induced in the amygdala after two kinds of stress, that is, such as electric shock and corticosterone injection. It was found that stress by electric shock decreased the expression of tyrosine hydoroxylase (TH) in the amygdala while the expression of pERK was increased. However, there is no difference in the expressions of TH and pERK in the frontal cortex compared with those of the control group. The level of corticosterone was significantly increased in the serum after stress. To determine the effect of corticosterone on the induction of anxiety and the expression of TH, the rats received corticosterone (20 mg or 40 mg/kg i.p.) for 1 day, 1 week, 2 weeks and 3 weeks, respectively. The spent time in open arms of the EPM (elevated plus maze) test was significantly decreased after 1 week, 2 weeks and 3 weeks. The time spent in open arms of the EPM test after repeated injections of corticosterone was significantly decreased in a dose-dependent manner. The expression of TH in the amygdala was reduced after following repeated corticosterone treatment for 2 weeks and 3 weeks. Collectively, this study suggests that corticosterone has a major role in the induction of anxiety and the modulation of TH expression, at least, in the amygdala.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.59-67
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• 2024

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid β (Aβ) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract. Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aβ_25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting. Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brainderived neurotrophic factor (BDNF) expression levels in Aβ_25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D. Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aβ accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

• BMB Reports
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• v.40 no.2
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• pp.196-204
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• 2007

Our previous study has shown that sodium selenite can cause apoptosis in acute promyelocytic leukemia-derived NB4 cells in a caspase-dependent manner, but the detailed mechanism is unknown. Here we demonstrate a requirement for extracellular signal-regulated protein kinase (ERK) in mediating sodium selenite -induced apoptosis in NB4 cell. Though no apparent elevation of ERK activity was observed during the apoptosis in NB4 cells caused by 20 μM sodium selenite treatment, PD98059 and U0126, specific chemical inhibitors of the MEK/ERK signaling pathway, were shown to strongly prevent the apoptosis process, while ERK activator TPA enhanced the process. It is also known that p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 had slight effects on apoptosis. Further study indicated that ERK exerted its proapoptotic effect only at the early stage of apoptosis and played an antiapoptotic role at the later stages. Taken together, our findings suggest that ERK plays an active role in mediating sodium seleniteinduced apoptosis in NB4 cells .

• Journal of Veterinary Clinics
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• v.30 no.5
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• pp.339-345
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• 2013

Mitogen-activated protein kinases (MAPKs) are a family of central signaling molecules that respond to numerous stimuli and are known to participate in processes of cell survival and death. However, it is not clear on data for cell-type specific activation of MAPKs in the progression of gastric ulcer. In the present study, we assessed how MAPKs localized at various cell types during the progression of gastric ulcer induced by ibuprofen. Gastric ulcer was induced by the repeated treatment of 200 mg/kg ibuprofen with 8 hrs interval in a day. Animals were sacrificed at 24 hrs, 48 hrs, and 72 hrs after oral treatment of ibuprofen and gastric tissues were subjected to immunohistochemical and immunoblotting evaluation. Immunoreactivity of phospho-extracellular signal-regulated kinase (p-ERK) was mainly expressed at the proliferating zone of gastric mucosa in control rats. But, these signals for p-ERK were highly shifted from cells of proliferating zone to parietal cells of the basal regions 24 hrs after treatment of ibuprofen. p-ERK signal was strongly expressed in epithelial cells adjacent to ulcer margin and new capillary and infiltrated inflammatory cells within granulation tissue of the ulcer base above 48 hrs after treatment of ibuprofen. While, phospho-c-Jun $NH_2$ terminal kinase (p-JNK) was mainly localized to the nuclei of the surface epithelial cells and the glandular epithelial cells in early gastric injury. Also, p-JNK was often observed as a scattered pattern in different regions of gastric mucosa with early gastric injury. Gradually, signal of p-JNK was strongly stained in infiltrated inflammatory cells and fibroblasts within severe ulcer base. Phospho-p38 (p-p38) MAPK was observed as scattered pattern within connective tissues of gastric mucosa. Especially, p-p38 MAPK showed strong signal in infiltrated macrophages within ulcer base. These results show that each MAPK has a specific role in various cell types during the progression of gastric ulcer.