• Nutrition Research and Practice
• /
• v.11 no.5
• /
• pp.357-364
• /
• 2017

BACKGROUND/OBJECTIVES: Oxidative stress is closely related with inflammation and development of many diseases. Black soybean seed coat contains high amount of anthocyanins, which are well-known for free radical scavenging activities. This study investigated inflammatory response and action mechanism of black soybean anthocyanins with regard to antioxidant activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS: RAW 264.7 cells were treated with anthocyanins extracted from black soybean seed coats in a concentration range of 12.5 to $100{\mu}g/mL$. The production of reactive oxygen species (ROS), secretion of pro-inflammatory mediators and cytokines, and the signaling in the mitogen activated protein kinases (MAPKs) pathway were examined. RESULTS: Black soybean anthocyanins significantly decreased LPS-stimulated production of ROS, inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$, and pro-inflammatory cytokines, including tumor necrosis factor ${\alpha}$ and interleukin-6, in a dose-dependent manner without cytotoxicity (P < 0.001). Black soybean anthocyanins downregulated the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells (P < 0.001). Moreover, black soybean anthocyanins inhibited LPS-induced phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 (P < 0.001). CONCLUSION: These results suggest that black soybean anthocyanins exert anti-inflammatory activity by inhibiting ROS generation and subsequent MAPKs signaling, thereby inhibiting inflammatory responses.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.337.1-337.1
• /
• 2002

Hypertrophy and the alteration of renal cell growth have been reported as early abnormality in diabetic nephropathy. However, the effects ot high PKCglucose and its action mechanism in renal proximal tubular cell (PTC) have not been elucidated. High glucose condition increases diacyl glycerol (DAG) and activates protein kinase C (PKC) in renal tubular cells. The PKC activates mitogen-activated protein kinases (MAPK), such as extracellular regulated kinase (ERK) and p38 MAPK. (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.8539-8548
• /
• 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.

• Biomedical Science Letters
• /
• v.12 no.3
• /
• pp.217-224
• /
• 2006

It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

• Journal of Ginseng Research
• /
• v.39 no.3
• /
• pp.279-285
• /
• 2015

Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.

• Journal of Veterinary Clinics
• /
• v.25 no.5
• /
• pp.355-358
• /
• 2008

The aim of this study was to investigate whether trophic factor supplementation (TFS) enhance the survival of kidney cell during cold ischemic storage and rewarming. The effect of TFS on the phosphorylation of p44/42 and p38 mitogen activated protein kinases (MAPK) signaling pathway was determined by Western blot. Apoptotic changes after cold ischemic storage and rewarming was determined by 4',6'-diamino-2-phenylindole (DAPI) staining. The cell viability was evaluated by live assay. TFS significantly decreased p44/42 and p38 MAPK activity induced by cold ischemic injury and rewarming (p < 0.05). The number of apoptotic cells was decreased after 5 minute rewarming in the presence of TFS. TFS significantly increased the cell viability after 5 minute rewarming (p < 0.05). Therefore, it was concluded that trophic factor supplementation protects kidney tubule cells from cold ischemic and rewarming injury via the inhibition of p44/42 and p38 MAPK activation and reducing apoptotic change.

• Toxicological Research
• /
• v.17
• /
• pp.89-96
• /
• 2001

Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.104-104
• /
• 2001

Ras는 세포의 성장과 분화 등 여러 필수적인 세포기능에 없어서는 안될 중요한 역할을 담당하며 Ras가 mutation되면 암 등의 치명적인 결과를 초래한다. Ras 발현은 유방암에서 tumor aggressiveness의 지표로 간주되고 있으며 유방세포의 침습성과 연관이 있다고 알려져 있으므로 ras가 전이과정에 미치는 영향에 관한 연구는 중요한 의미를 갖는다. 본 연구의 선행연구결과, H-ras와 N-ras 모두 transformed phenotype을 나타내지만 H-ras 만이 암전이에 있어서 중요한 침윤성을 유도하는 것을 밝혔다. 이 결과는 MCF10A 세포에서 H-ras와 N-ras에 의한 신호전달경로가 각각 다른 생물학적 전이활성을 나타냄을 시사한다. 세포의 이동성은 침습성에 있어서 결정적인 역할을 하므로, 본 연구에서 H-ras와 N-ras로 형질전환된 MCF10A세포에서 이동성을 시험한 결과, 세포의 이동성이 N-ras가 아닌 H-ras MCF10A 세포에서만 크게 증가된다는 것을 보았다. 이는 침습성을 나타내는 H-ras가 세포의 이동성을 증가시키는데 작용한다는 것을 말한다. H-ras에 의해 유도된 침습성과 이동성에 대한 분자적 기전에 관하여 연구하기 위하여 H-ras MCF10A와 N-ras MCF10A 세포에서 Ras의 downstream effector들, 특히 mitogen-activated protein kinases(MAPKinases)들인 JNK1, ERK, p38의 활성화를 살펴본 결과 p38 MAPKinase가 H-ras MCF10A 세포에서 현저하게 활성화됨을 보았다. p38 MAPKinase 저해제인 SB203580를 처리하던지 dominant negative p38 (DN p38) transfectant로 p38을 불활성화시켰을 때 세포침습성 및 이동성이 저해되는 결과를 얻었다. SB203580 처리한 H-ras MCF10A 세포에서 전이에 관여하는 효소인 MMP-2 분비가 감소되었다. H-ras에 의해 유도된 침습성과 이동성은 DN JNK1 transfectant에서는 변화가 없었으나 DN MEK transfectants에서는 유의성있게 감소되었다. 이상의 결과를 종합하면, MCF10A 세포의 침윤성과 이동성에는 p38 MAPKinase 활성이 중심적인 역할을 하며, JNK 활성은 영향을 미치지 않고, ERK-1/2 활성은 충분하지는 않으나 필요하다는 것을 알 수 있었다.

• Proceedings of the Korean Society of Veterinary Pathology Conference
• /
• 2003.10a
• /
• pp.42-42
• /
• 2003

The contamination of the environment with pollutants is one of the main problems of modern life, and the levels pollution in industrialized regions are giving raise to increased public concern. The mitogen-activated protein kinase (MAP kinase) are playa pivotal role in the regulation of important cellular functions by activation of specific signal transduction pathways from cell the surface to the nuclei. Three major subgroups of MAP kinases have been identified, and these comprise the extracellular signal-regulated kinase (ERK), the c-Jun amino-terminal kinase (JNK), and the p38 MAP kinases [1-3]. Herein, we investigated the effect of regulation of phospho-JNK (p-JNK), phospho-p38 (p-p38) and phospho-ERK (p-ERK) by TCDD. (omitted)

• The Journal of Korean Physical Therapy
• /
• v.20 no.3
• /
• pp.61-68
• /
• 2008

Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.