• 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.

• 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.

• 생명과학회지
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• 제20권11호
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• pp.1603-1610
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• 2010

Fucoidan은 갈조류의 세포벽에 존재하는 황산화 다당류이다. 본 연구에서는 자외선 B를 인체각질형성세포에 조사하여 matrix metalloproteinase-1 (MMP-1)을 발현 시킨 후 Fucus evanescens fucoidan이 MMP-1 promoter, mRNA, 단백 발현과 mitogen-activated protein kinases (MAPKs)의 인산화에 미치는 영향을 확인하고자 하였다. 자외선 B에 의해 생성된 MMP-1의 promoter activity와 mRNA, 단백 발현은 fucoidan $10\;{\mu}g/ml$와 $100\;{\mu}g/ml$를 투여하였을 때 fucoidan을 투여하지 않고 자외선만 조사한 군에 비하여 유의하게 억제되었다. 그리고 F. evanescens fucoidan은 extracellular signal regulated kinase (ERK)의 활성은 현저히 억제시켰으나 c-JUN N-terminal kinase (JNK)와 p38의 활성에 미치는 영향은 약하였다. 따라서 이 연구결과들은 F. evanescens fucoidan이 피부 광노화의 예방과 치료에 도움이 될 가능성을 확인할 수 있었다.

• 대한화장품학회지
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• 제39권2호
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• pp.159-166
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• 2013

본 연구에서는 새로운 미백소재를 개발하기 위해 적양 에탄올추출물을 효소처리 후 EtOAc 분획물(AJE)을 준비하여 in vitro 상에서 이들의 tyrosinase 저해활성과 세포 수준에서의 멜라닌 합성 저해효과를 측정하였다. AJE는 mushroom tyrosinase의 활성에는 영향을 미치지 않았으나 B16-F1 melanoma cell을 이용한 멜라닌 합성 저해효과에 있어서 농도 의존적으로 멜라닌 합성을 저해하여, $40{\mu}g/mL$의 농도에서 52% 이상의 저해효과를 나타내었다. 이러한 멜라닌 합성 저해효과에 대한 작용 기전을 확인하기 위해 western blot을 통해 멜라닌 합성 경로에 관련된 단백질의 발현을 측정하였다. 그 결과 멜라닌 합성에 관여하는 효소인 tyrosinase related protein 1 (TRP-1)의 발현을 억제하였고, 이를 조절하는 전사인자인 microphthalmia associated transcription factor (MITF) 발현 역시 효과적으로 억제하였다. 또한 extracellular signal-regulated kinase (ERK) pathway를 활성화시킴으로써 phosphorylated extracellular signal-regulated kinase (p-ERK)의 발현을 상당히 증가시키는 것을 확인할 수 있었다. 이러한 결과는 AJE가 멜라닌 합성의 신호전달 경로 중 ERK pathway의 활성화를 통해 MITF의 분해를 촉진시키고 이로 인해 MITF의 발현을 감소시키며, 그 결과 멜라닌 합성에 관여하는 효소 중 TRP-1의 발현을 감소시킴으로써 멜라닌 합성을 저해하는 것으로 사료되며, 따라서 AJE는 미백용도의 기능성 원료로서의 가능성이 큰 것으로 판단된다.

• The Korean Journal of Physiology and Pharmacology
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• 제15권4호
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• pp.245-249
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• 2011

Amphetamine, a synthetic psychostimulant, is transported by the dopamine transporter (DAT) to the cytosol and increases the exchange of extracellular amphetamine by intracellular dopamine. Recently, we reported that the phosphorylation levels of ezrin-radixin-moesin (ERM) proteins are regulated by psychostimulant drugs in the nucleus accumbens, a brain area important for drug addiction. However, the significance of ERM proteins phosphorylation in response to drugs of abuse has not been fully investigated. In this study, using PC12 cells as an in vitro cell model, we showed that amphetamine increases ERM proteins phosphorylation and protein kinase C (PKC) ${\beta}$ inhibitor, but not extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinases (PI3K) inhibitors, abolished this effect. Further, we observed that DAT inhibitor suppressed amphetamine-induced ERM proteins phosphorylation in PC12 cells. These results suggest that $PKC{\beta}$-induced DAT regulation may be involved in amphetmaine-induced ERM proteins phosphorylation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2495-2499
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• 2015

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation, terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of RCCC and 28 control cases. Expression levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+ FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05). CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors.

• 셀메드
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• 제13권6호
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• pp.7.1-7.6
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• 2023

Raphanus sativus L. has been reported to have anti-inflammatory and anti-tumor activity. However, the anti-inflammatory effect and mechanism of action of the Raphanus sativus L. seeds (RSS) with or without oil are still unknown. This study was undertaken to investigate the in-vitro anti-inflammatory effect with or without oil in the RSS on RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Results showed the suppressed LPS-induced secretion of pro-inflammatory mediators such as nitric oxide (NO), inflammatory cytokine (IL-6, TNF-α). Additionally, a decrease in protein expression of iNOS was observed, but nuclear translocation of NF-κB p65 was not inhibited. To elucidate the underlying mechanism of the anti-inflammatory effect of RSS, the involvement of mitogen-activated protein kinase (MAPK) signaling pathways was examined. We also found that RSS blocked LPS-induced phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK) signaling but did not affect the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2. These results suggest that RSS may have potential as an anti-inflammatory agent through the inhibition of LPS-induced inflammatory cytokine production via regulation of the JNK pathway.

• International Journal of Oral Biology
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• 제45권4호
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• pp.218-224
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• 2020

The antitumor effects of octyl gallate (OG) were investigated on FaDu human hypopharyngeal squamous carcinoma cells. At various concentrations, OG inhibited the proliferation of FaDu cells by suppressing cell cycle regulators and induced apoptosis by activating caspase 3 and its downstream poly (ADP-ribose) polymerase, thereby damaging DNA. Immunoblotting demonstrated that OG significantly suppressed the expression of integrin family proteins (integrin α4, αv, β3, β4), hindering cell adhesion. The reduced expression of integrins subsequently mediated the mitogen-activated protein kinase signaling pathway to stimulate the activation of extracellular signal-regulated kinases and c-jun N-terminal kinases, leading to apoptosis. Thus, OG demonstrated antitumor activity on hypopharyngeal squamous carcinoma cells by suppressing cell proliferation and inducing apoptosis.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.76.2-76.2
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• 2003

Although sphingosine-1-phosphate (S1P) is a well-known mitogen, our results show that S1P potently inhibits keratinocyte proliferation, and that this leads the inhibition of DNA synthesis. Interestingly, the prolonged activation of extracellular signal-regulated protein kinase (ERK) and the transient inactivation of Akt/protein kinase B (PKB) were also oberved in concert with the inhibition of keratinocyte proliferation by S1P. To further verify the anti-proliferative action of S1P, we examined changes in cell cycle related proteins. (omitted)

• Journal of Ginseng Research
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• 제39권4호
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• pp.299-303
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• 2015

Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products-ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect.