• 대한수의학회지
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• 제43권4호
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• pp.525-529
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• 2003

The phosphorylation of extracellular signal-regulated kinases (p-ERK) in the spinal cord of rats with acute monophasic experimental autoimmune encephalomyelitis (EAE) was studied using immunohistochemistry and treatment with inhibitor. P-ERK is constitutively expressed in glial cells in the normal spinal cord. In EAE, some inflammatory cells in the subarachnoid space were positive for p-ERK at the early stage, and its immunoreactivity declined when those cells infiltrated the parenchyma at the peak stage. In a blocking experiment using its inhibitor, the intravenous administration of PD98059 from day 7 to 13 post-immunization did not modulate EAE paralysis. Considering the results, we postulate that intravenous administration of PD98059 is not effective in ameliorating EAE paralysis, although many inflammatory cells express ERK in the subarachnoid space.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6391-6395
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• 2014

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

• 제어로봇시스템학회논문지
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• 제10권12호
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• pp.1155-1163
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• 2004

Extracellular signal-regulated kinase (ERK) signaling pathway is one of the mitogen-activated protein kinase (MAPK) signal transduction pathways. This pathway is known as pivotal in many signaling networks that govern proliferation, differentiation and cell survival. The ERK signaling pathway comprises positive and negative feedback loops, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level. In this paper, we attempt to model the ERK pathway by considering both of the positive and negative feedback mechanisms based on Michaelis-Menten kinetics. In addition, we propose a fraction ratio model based on the mass action law. We first develop a mathematical model of the ERK pathway with fraction ratios. Secondly, we analyze the dynamical properties of the fraction ratio model based on simulation studies. Furthermore, we propose a concept of an inhibitor, catalyst, and substrate (ICS) controller which regulates the inhibitor, catalyst, and substrate concentrations of the ERK signal transduction pathway. The ICS controller can be designed through dynamical analysis of the ERK signaling transduction pathway within limited concentration ranges.

• 동의생리병리학회지
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• 제21권1호
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• pp.76-81
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• 2007

The effect of either low or high intensity four weeks exercise treadmill running on the activation of the extracellular-signal regulated protein kinase (ERK1/2) and the c-Jun N-terminal kinase(JNK) pathways was determined in rat tibialis muscle. Sprague-Dawley rats were assigned to one of three groups: (i) sedentary group(NE; n=10); (ii) low intensity exercise group (8m/min; LIE; n=10); and (iii) high intensity exercise group(28m/min; HIE; n=10). The training regimens were planned so that animals covered the same distance and had similar glycogenutilization for both LIE and HIE exercise sessions. After four weeks exercise, 48 h after the last exercise bout obtained samples. pERK1 increased 1.5 times comparing with the sedentary group in the low intensity group while it increased 11.7 times in high intensity group, in the tibialis of rats. In the low intensity group, pERK2 increased 1.4 times comparing with the sedentary group while it increased 3.3 times in high intensity group. While pJNK1 decreased 0.9 times, comparing with the sedentary group, pJNK2 was increased to 0.5 times in the low intensity group. But in high intensity group, pJNK2 decreased 0.7 times while pJNK1 didn't show any change. In conclusion, Four weeks exercise of different intensities results in tibialis muscle activation of intracellular signal pathways, which may be one mechanism regulating specific adaptations induced by different exercise intensities.

• 한방안이비인후피부과학회지
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• 제22권2호
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• pp.104-117
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• 2009

Objective : Melanin is one of the most important facor in skin color. Melanin protects human skin from ultraviolet radiation otherwise it causes melanin pigmentation. So this experiment is carried out for test whether Scutellaria baicalensis Georgi(SBG) inhibits melanin synthesis and tyrosinase activity in mouse B16 melanoma cells. Method : The melanin synthesis inhibition effects of SBG were examined by in vitro melanin production assay. We assessed inhibitory effects of SBG on melanin contents from B16F1 melanoma cell, on tyrosinase activity(cell and cell free system), effect of SBG on the expression tyrosinase, Microphthalmia-associated Transcription Factor(MITF), Extracellular signal-regulated Kinase(ERK). Result : SBG inhibited melanin synthesis induced $\alpha$-MSH($\alpha$-Melanin Stimulating Hormone) in B16F1. SBG inhibited tyrosinase activity and expression. And SBG down-regulates MITF and stimulated ERK activation in B16F1. Conclusion : According to above results, SBG was improved its suppression effect to the inhibition of melanin synthesis, tyrosinase activation, and tyrosinase promotor activation. So SBG is considered to be used for an strong source of skin whitening effect.

• Natural Product Sciences
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• 제13권2호
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• pp.169-173
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• 2007

Luteolin is a major flavonoid of Lonicera japonica and has anti-inflammatory effect. The activation of proteinase-activated receptor (PAR)-2 and -4 by trypsin appears to play a role in inflammation, In the present study, we examined the inhibitory effects of luteolin on activation of trypsin-induced human leukemic mast cells (HMC-1). HMC-1 cells were stimulated with trypsin, PAR-2 and PAR-4 agonist, in the presence or absence of luteolin. The level of TNF-${\alpha}$ secretion was measured by enzyme-linked immunosorbent assay (ELISA). The expression of tryptase and phosphorylated-extracellular signal-regulated kinase (ERK) were assessed by Westem blot analysis. Moreover, trypsin activity was measured by the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). TNF-${\alpha}$ secretion and Tryptase expression in trypsin-stimulated HMC-1 cells were markedly inhibited by pretreatment of luteolin. Furthermore, the pretreatment of luteolin resulted in the reduction of ERK phosphorylation and trypsin activity. These results suggest that luteolin might has the inhibitory effects on the PAR-2 and -4-dependent inflammation.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.309-318
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• 2024

Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid (QA) and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering QA restored social impairment and LPS-induced spatial and fear memory. In addition, QA inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. QA inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, QA restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.

• BMB Reports
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• 제37권4호
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• pp.480-486
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• 2004

Brain ischemia brings about hypoxic insults. Hypoxia is one of the major pathological factors inducing neuronal injury and central nervous system infection. We studied the involvement of mitogen-activated protein (MAP) kinase in hypoxia-induced apoptosis using cobalt chloride in C6 glioma cells. In vitro cytotoxicity of cobalt chloride was tested by MTT assay. Its $IC_{50}$ value was $400\;{\mu}M$. The DNA fragment became evident after incubation of the cells with $300\;{\mu}M$ cobalt chloride for 24 h. We also evidenced nuclear cleavage with morphological changes of the cells undergoing apoptosis with electron microscopy. Next, we examined the signal pathway of cobalt chloride-induced apoptosis in C6 cells. The activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) started to increase at 1 h and was activated further at 6 h after treatment of 400 M cobalt chloride. In addition, pretreatment of PD98059 inhibited cobalt chloride-induced apoptotic cell morphology in Electron Microscopy. These results suggest that cobalt chloride is able to induce the apoptotic activity in C6 glioma cells, and its apoptotic mechanism may be associated with signal transduction via MAP kinase (ERK 1/2).

• Molecules and Cells
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• 제21권2호
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• pp.237-243
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• 2006

Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.

• Animal cells and systems
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• 제8권1호
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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.