• 동의생리병리학회지
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• 제22권5호
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• pp.1299-1303
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• 2008

Since exercise training induces mechanical stress to the heart, we examined the activation pattern of mitogen-activated protein kinase(MAPK)s signaling pathway by immunohistochemistry. The immunoreactions of MAPKs signaling with c-fos and Schiff's reaction were increased in the cardiac muscle of exercised rat compared to normal one except immunoreaction for MEK1/2 and ERK1/2 and p38. However, the immunoreaction of phospho-JNK and phospho-p38 with early gene c-fos were arrested markedly in water extract of Alliium sativum (WEAS) treated rat compared to exercised one. Since MAPKs signaling does play a protective role in response to pathological stimulus in the heart, results in the present study suggest that WEAS may act as a alleviating agent for exercise-induced stress to. heart through regulating MAPKs signaling activation.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.56-56
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• 2021

Nypa fruticans Wurmb is a mangrove plant belonging to Araceae family. N. fruticans is typically found in Southeast Asia, and in some parts of Queensland, Australia. N. fruticans has phytochemicals, phenolics, and flavonoids. In this study, we investigated the anti-inflammatory effects of the ethyl acetate fraction of N. fruticans (ENF) on the production and expression of cytokines and inflammatory mediators through the major signal transduction pathways. ENF attenuated the level of cytokines in a dose-dependent manner and decreased the production of nitric oxide (NO). ENF decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via alleviating transcription of nuclear factor-kappa B (NF-κB) by an inhibitor of nuclear factor-kappa B (IκB) degradation. Furthermore, mitogen-activated protein kinase (MAPK) signaling pathways (ERK1/2, JNK1/2, and p38) are known to be involved in the inflammatory response. Phosphorylations of ERK1/2, JNK1/2, and p38 were significantly decreased compared with the ENF-untreated control. Conclusively, ENF was related to alleviating various pro-inflammatory mediators through IκB/NF-κB and MAPK signaling pathways, including p65 translocation to the nucleus.

• 대한물리치료과학회지
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• 제11권1호
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• pp.20-27
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• 2004

It is widely accepted that smooth muscle contraction is triggered by intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR) and from the extracellular space, The increased $[Ca^{2+}]_i$ can phosphorylate the 20-kDa myosin light chain ($MLC_{20}$) by activating MLC kinase (MLCK), and this initiates smooth muscle contraction. In addition to the $[Ca^{2+}]_i$-MLCK-tension pathway, a number of intracellular signal molecules, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and Rho-associated coiled coil-forming protein kinase (ROCK), play important roles in the regulation of smooth muscle contraction. However, the mechanisms regulating contraction of caldesmon (CaD), actin-binding protein, are not entirely elucidated in the presence of $Ca^{2+}$. It is known that CaD tightly interacts with actin and inhibits actomyosin ATPase activity. Therefore, the purpose of the present study was to investigate the roles of $Ca^{2+}$-dependent CaD in smooth muscle contraction. Endothelin-1 (ET-1), G-protein coupled receptor agonist and vasoconstrictor, increased both vascular smooth contraction and phosphorylation of CaD in the presence of $Ca^{2+}$. These results suggest that ET-1 induces contraction and phosphorylation of CaD in rat aortic smooth muscle, which may he mediated by the increase of $[Ca^{2+}]_i$.

• 생명과학회지
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• 제13권6호
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• pp.903-910
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• 2003

Phosphipase D(PLD)는 호중구의 활성에서 중요한 신호전달 인자로 작용한다. 본 연구에서는 호중구에서 PLD의 활성화에 대한 nitric oxide(NO)와 cGMP의 영향을 조사하였다. 세포 내 NO의 생성을 증가시키는 물질인 sodium nitroprusside (SNP)를 단독으로 처리하였을 때 SNP를 처리하지 않은 세포에 비교하여 PLD 활성은 0.5 mM 농도에서 2배 이상 증가하였다. 세포 내 cAMP의 농도를 증가시키는 물질인 dibutyryl-cAMP를 처리하였을 때 formyl-Met-Leu-Phe(fMLP)에 의한 PLD활성은 억제되었으나 cGMP를 증가시키는 물질인 8-bromo-cGMP(300 $\mu$M)를 단독으로나 fMLP와 같이 처리하였을 때 PLD의 활성은 큰 영향이 없었다. NO에 의한 PLD의 활성은 cGMP-의존형 인산화 효소인 protein kinase G(PKG)의 억제제인 KT 5823에 의하여 억제되지 않았는데 이러한 결과는 PKG 이외의 경로를 통하여 일어남을 제시한다. NO를 처리한 호중구에서 p38 mitogen activated protein kinase(MAPK)가 활성화되어 인산화된 p38 MAPK가 Western blot에서 증가되었다. NO에 의한 p38 MAPK의 인산화는 KT 5823에 의하여 억제되지 않았고 PLD 억제제인 n-butanol에 의하여도 영향을 받지 않았다. PLD 활성의 인자인 RhoA는 fMLP나 phorbol myristate acetate(PMA)의 자극에 의하여 세포질로부터 세포막으로 전이가 되었으나 cGMP의 전처리에 의하여 fMLP에 의한 RhoA의 전이는 억제되었으나 PMA에 의한 전이는 영향을 받지 않았다. 이들 결과들은 호중구 내 증가된 cGMP가 RhoA를 억제하였으나 세포 내 증가된 NO는 cGMP 이외의 인자를 통하여 PLD의 활성화를 일으킨다는 것을 제시하고 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8539-8548
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• 2014

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

• Asian-Australasian Journal of Animal Sciences
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• 제27권5호
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• pp.733-742
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• 2014

The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ) proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets' intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK) signaling pathway in piglets' intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco's modified Eagle's medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs' jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.

• Plant Biotechnology Reports
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• 제5권1호
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• pp.19-25
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• 2011

Tocopherols belong to the plant-derived poly phenolic compounds known for antioxidant functions in plants and animals. Activation of mitogen-activated protein kinases (MAPK) is a common reaction of plant cells in defense-related signal transduction pathways. We report a novel non-antioxidant function of ${\alpha}$-tocopherol in higher plants linking the physiological role of tocopherol with stress signalling pathways. Pre-incubation of a low concentration of $50{\mu}M$ ${\alpha}$-tocopherol negatively interferes with MAPK activation in elicitor-treated tobacco BY2 suspension culture cells and wounded tobacco leaves, whereas pre-incubated BY2 cells with ${\alpha}$-tocopherol phosphate did not show the inhibitory effect on stimuli-induced MAPK activation. The decreased MAPK activity was neither due to a direct inhibitory effect of ${\alpha}$-tocopherol nor due to the induction of an inhibitory or inactivating activity directly affecting MAPK activity. The data support that the target of ${\alpha}$-tocopherol negatively regulates an upstream component of the signaling pathways that leads to stress dependent MAPK activation.

• Journal of Ginseng Research
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• 제38권1호
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• pp.16-21
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• 2014

Ginseng saponins exert various important pharmacological effects with regard to the control of many diseases, including cancer. In this study, the anticancer effect of ginsenosides on human cancer cells was investigated and compared. Among the tested compounds, ginsenoside-Rh2 displays the highest inhibitory effect on cell viability in HepG2 cells. Ginsenoside-Rh2, a ginseng saponin isolated from the root of Panax ginseng, has been suggested to have potential as an anticancer agent, but the underlying mechanisms remain elusive. In the present study, we have shown that cancer cells have differential sensitivity to ginsenoside-Rh2-induced apoptosis, raising questions regarding the specific mechanisms responsible for the discrepant sensitivity to ginsenoside-Rh2. In this study, we demonstrate that AMP-activated protein kinase (AMPK) is a survival factor under ginsenoside-Rh2 treatment in cancer cells. Cancer cells with acute responsiveness of AMPK display a relative resistance to ginsenoside-Rh2, but cotreatment with AMPK inhibitor resulted in a marked increase of ginsenoside-Rh2-induced apoptosis. We also observed that p38 MAPK (mitogen-activated protein kinase) acts as another survival factor under ginsenoside-Rh2 treatment, but there was no signaling crosstalk between AMPK and p38 MAPK, suggesting that combination with inhibitor of AMPK or p38 MAPK can augment the anticancer potential of ginsenoside Rh2.

• Korean Journal of Acupuncture
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• 제31권1호
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• pp.14-19
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• 2014

목적 : 본 연구에서는 정향 에탄올 추출물이 RBL-2H3 세포 매개 알레르기 반응에 대해 미치는 영향과 그 작용기전에 대해 연구했다. 방법 : 정향 에탄올 추출물의 RBL-2H3 세포에 대한 독성 여부는 MTT 분석을 통해 평가했다. 정향 에탄올 추출물의 항알러지 작용은 효소결합면역 분석방법(ELISA)을 이용해 ${\beta}$-Hexosaminidase과 Histamine의 분비량을 측정하여 평가하였다. 정향 에탄올 추출물의 작용기전에 대해서는 유사 분열물질-활성화단백질인산화효소(mitogen-activated protein kinase, MAPK)를 western blot 법을 이용하여 측정함으로써 평가하였다. 결과 : 정향의 에탄올 추출물은 RBL-2H3 세포에 대해 독성을 나타내지 않는 농도에서 RBL-2H3 세포의 탈과립과 히스타민 분비를 유의하게 억제하였으며, p38 MAPK의 활성을 차단하였다. 결론 : 본 연구의 결과 정향의 에탄올 추출물은 비만세포에서 유래된 알러지 반응을 억제하는 효과가 있으며, 또한 그 작용기전은 p38 MAPK 인산화와 연계되어 있을 것으로 사료된다.

• Journal of Photoscience
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• 제9권2호
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• pp.25-28
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• 2002

The chicken pineal gland has been used for studies on the circadian clock, because it retains an intracellular phototransduction pathway regulating the phase of the intrinsic clock oscillator. Previously, we identified chicken clock genes expressed in the gland (cPer2, cPer3, cBmal1, cBmal2, cCry1, cCry2, and cClock), and showed that a cBMALl/2-cCLOCK heteromer acts as a regulator transactivating cPer2 gene through the CACGTG E-box element found in its promoter. Notably, mRNA expression of cPer2 gene is up-regulated by light as well as is driven by the circadian clock, implying that light-dependent clock resetting may involve the up-regulation of cPer2 gene. To explore the mechanism of light-dependent gene expression unidentified in animals, we first focused on pinopsin gene whose mRNA level is also up-regulated by light. A pinopsin promoter was isolated and analyzed by transcriptional assays using cultured chicken pineal cells, resulting in identification of an 18-bp light-responsive element that includes a CACGTG E-box sequence. We also investigated a role of mitogen-activated protein kinase (MAPK) in the clock resetting, especially in the E-box-dependent transcriptional regulation, because MAPK is phospholylated (activated) in a circadian manner and is rapidly dephosphorylated by light in the gland. Both pulldown analysis and kinase assay revealed that MAPK directly associates with BMAL1 to phosphorylate it at several Ser/Thr residues. Transcriptional analyses implied that the MAPK-mediated phosphorylation may negatively regulate the BMAL-CLOCK-dependent transactivation through the E-box. These results suggest that the CACGTG E-box serves not only as a clock-controlled element but also as a light-responsive element.