• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.24-31
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• 2010

Taurine, 2-aminoethanesulfonic acid, is an abundant free amino acid present in brain cells and exerts many important biological functions such as anti-convulsant, modulation of neuronal excitability, regulation of learning and memory, anti-aggressiveness and anti-alcoholic effects. In the present study, we investigated to explore whether taurine has any protective actions against oxidative stress-induced damages in neuronal cells. ERK I/II regulates signaling pathways involved in nitric oxide (NO) and reactive oxygen species (ROS) production and plays a role in the regulation of cell growth, and apoptosis. We have found that taurine significantly inhibited AMPA induced cortical depolarization in the Grease Gap assays using rat cortical slices. Taurine also inhibited AMPA-induced neuronal cell damage in MTT assays in the differentiated SH-SY5Y cells. When the neuronal cells were treated with $H_2O_2$, levels of NO were increased; however, taurine pretreatment decreased the NO production induced by $H_2O_2$ to approximately normal levels. Interestingly, taurine treatment stimulated ERK I/II activity in the presence of AMPA or $H_2O_2$, suggesting the potential role of ERK I/II in the neuroprotection of taurine. Taken together, taurine has significant neuroprotective actions against AMPA or $H_2O_2$ induced damages in neuronal cells, possibly via activation of ERK I/II.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.115-123
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• 2006

Objective: To investigate new signal transduction cascade through integrin, FAK and ERK in the suppressed cell proliferation by GnRH-I and -II. Method: Human endometrial cancer cells (HEC1A) were cultured under the following condition: DMEM/F12 (10% FBS). GnRH-I and -II were treated time (0, 5, 10, 15, 20, 30 min; 100 nM) and dose (10 nM or 100 nM; 20 min) dependent manner according to experimental purposes. Cell proliferation was measured using [$^3H$] thymidine incorporation assay. Immunoblotting was utilized to detect proteins. Results: GnRH-I and -II inhibited proliferation of HEC1A cells and induced expression of integrin ${\beta}3$. Phosphorylation of FAK and ERK were induced by GnRH-I and -II. Conclusion: GnRH inhibited cell proliferation via the expression of integrin and FAK, ERK phosphorylation.

• Journal of Korean Academy of Nursing
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• v.44 no.4
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• pp.371-380
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• 2014

Purpose: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. Methods: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. Results: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. Conclusion: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.37-46
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• 2006

Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.

• Applied Chemistry for Engineering
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• v.32 no.6
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• pp.647-652
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• 2021

In this study, Saussurea Lappa roots were extracted using ethanol and n-hexane, and also the effects on proliferation of human hair dermal papilla cells and fibroblast and related signaling pathway were evaluated. 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay was conducted for cell proliferation effect of Saussurea Lappa root extract, and extracellular signal-related kinase (ERK), serine/threonine protein kinase (Akt), wingless-related integration site (Wnt)/𝛽-catenin signaling pathway, and 5𝛼-reductase expression through western blot analysis were measured. Saussurea Lappa root extract significantly increased human hair dermal papilla cells and propagation of fibroblast, promoted phosphorylation of ERK and Akt that get involved in cell proliferation. Additionally, Saussurea Lappa root extract significantly decreased promotion of Akt phosphorylation and cell proliferation by MEK/ERK inhibitor PD98059 and PI3K/Akt inhibitor LY294002. Also, Saussurea Lappa root extract induced intranuclear 𝛽-catenin accumulation by promoting phosphorylation of 𝛽-catenin (Ser552, 675) through phosphorylation of GSK-3𝛽 (Ser9), and suppressed activation of 5𝛼-reductase type I and II. Overall, Saussurea Lappa root induces cell proliferation through vitalization of ERK and Akt route of human hair dermal papilla cells and fibroblast and apoptosis defense mechanism, and can be helpful in hair loss prevention and hair growth by vitalizing the 𝛽-catenin signaling pathway and inhibiting activation of 5𝛼-reductase, which can be used as a potential hair care products.

• Journal of Embryo Transfer
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• v.33 no.4
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• pp.287-296
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• 2018

Ganglioside GM3 is known as an inhibition factor of cell differentiation and proliferation via inhibition of epidermal growth factor receptor (EGFR) phosphorylation. Our previous study showed that the exogenous ganglioside GM3 reduced the meiotic maturation of porcine oocytes and induced apoptosis at 44 h of in vitro maturation (IVM). However, the role of ganglioside GM3 in the relationship between EGFR signaling and apoptosis during porcine oocyte maturation has not yet been studied. First, porcine cumulus-oocyte complexes (COCs) were cultured in the NCSU-23 medium with exogenous ganglioside GM3 according to maturation periods (non-treated, only IVM I: 0 - 22 h, only IVM II: 22 - 44 h and IVM I & II: 0 - 44 h). We confirmed that the proportion of germinal vesicle breakdown (GVBD) increased significantly in the IVM I treated group than in the control group. We also confirmed that the meiotic maturation until M II stage and polar body formation decreased significantly in the only IVM I treated group. Cumulus cell expansion and mRNA levels of the expansion-related factors (HAS2, TNFAIP6 and PTX3) decreased significantly in the IVM I treated group than in the control group. Protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 decreased significantly in the GM3-treated groups, during the IVM I period. In addition, cellular apoptosis, determined using TUNEL assay, and protein levels of Cleaved caspase 3, were increased significantly in the GM3-treated COCs during the IVM I period. Based on these results, ganglioside GM3 exposure of porcine COCs during the IVM I period reduced meiotic maturation and cumulus cell expansion via inhibition of EGFR activity in pigs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.63-67
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• 2019

Interaction between epidermis and dermis plays an important role in wound healing and hair follicle formation. This study focused on investigating the potency of ethanol extract of Puerariae Radix (EPR) as cosmetic ingredient using human dermal fibroblasts (hDFn). Our results revealed that EPR suppressed collagenase activity dose-dependently. EPR inhibited activity of $5{\alpha}$-reductase I and II at the final concentration of $25{\mu}g/ml$ in hDFn cells. Also, EPR promoted the proliferation and the ERK activation of cells. ERK phosphorylation by EPR was blocked by specific inhibitor of ERK, PD98059. EPR-induced cell proliferation was blocked by PD98059. This means that EPR could promote the proliferation of hDFn cells via the activation ERK. Collectively, these results suggest that EPR may be used as a new cosmetic ingredient.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.615-629
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• 2021

An active compound, triterpene saponin, astersaponin I (AKNS-2) was isolated from Aster koraiensis Nakai (AKNS) and the autophagy activation and neuroprotective effect was investigated on in vitro and in vivo Parkinson's disease (PD) models. The autophagy-regulating effect of AKNS-2 was monitored by analyzing the expression of autophagy-related protein markers in SH-SY5Y cells using Western blot and fluorescent protein quenching assays. The neuroprotection of AKNS-2 was tested by using a 1-methyl-4-phenyl-2,3-dihydropyridium ion (MPP⁺)-induced in vitro PD model in SH-SY5Y cells and an MPTP-induced in vivo PD model in mice. The compound-treated SH-SY5Y cells not only showed enhanced microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and decreased sequestosome 1 (p62) expression but also showed increased phosphorylated extracellular signal-regulated kinases (p-Erk), phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated unc-51-like kinase (p-ULK) and decreased phosphorylated mammalian target of rapamycin (p-mTOR) expression. AKNS-2-activated autophagy could be inhibited by the Erk inhibitor U0126 and by AMPK siRNA. In the MPP⁺-induced in vitro PD model, AKNS-2 reversed the reduced cell viability and tyrosine hydroxylase (TH) levels and reduced the induced α-synuclein level. In an MPTP-induced in vivo PD model, AKNS-2 improved mice behavioral performance, and it restored dopamine synthesis and TH and α-synuclein expression in mouse brain tissues. Consistently, AKNS-2 also modulated the expressions of autophagy related markers in mouse brain tissue. Thus, AKNS-2 upregulates autophagy by activating the Erk/mTOR and AMPK/mTOR pathways. AKNS-2 exerts its neuroprotective effect through autophagy activation and may serve as a potential candidate for PD therapy.

• Molecules and Cells
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• v.45 no.4
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• pp.257-272
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• 2022

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.7-13
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• 2004

Severe hypertension (>180 mmHg) develops in spontaneously hypertensive rats (SHR) after 12 wk-old; however, it is not clear whether what kinds of molecular mechanism leads to altered cardiac performance following developmental stages in SHR. Also, although the effect of calcineurin (Cn) to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. Thus, we have examined i) body weight and blood pressure, ii) differences of expression and distribution of signaling molecules such as Cn, protein kinase B/Akt (PKB/Akt), and extracellular signal-regulated kinase (ERK) between SHR and their age-matched control Wistar-Kyoto (WKY) rats following developmental stages. In 16 wk-old SHR compared with WKY, 2-dimentional echocardiography showed cardiac enlargement and hypertrophy of left ventricle, significantly. Taken together, we suggest that Cn is associated with hereditary cardiac hypertrophy, the process being related to the molecular signaling mechanisms involving PKB/Akt and ERK.