• The Plant Pathology Journal
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• 제31권2호
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• pp.192-194
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• 2015

Pathogen-associated molecular patterns (PAMPs) activate mitogen-activated protein kinases (MAPKs), essential components of plant defense signaling. Salicylic acid (SA) is also central to plant resistance responses, but its specific role in regulation of MAPK activation is not completely defined. We have investigated the role of SA in PAMP-triggered MAPKs pathways in Arabidopsis SA-related mutants, specifically in the flg22-triggered activation of MPK3 and MPK6. cim6, sid2, and npr1 mutants exhibited wild-type-like flg22-triggered MAPKs activation, suggesting that impairment of SA signaling has no effect on the flg22-triggered MAPKs activation. Pretreatment with low concentrations of SA enhanced flg22-induced MPK3 and MPK6 activation in all seedlings except npr1, indicating that NPR1 is involved in SA-mediated priming that enhanced flg22-induced MAPKs activation.

• Childhood Kidney Diseases
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• 제21권1호
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• pp.1-7
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• 2017

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and $TGF-{\beta}1$ expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.

• BMB Reports
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• 제34권6호
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• pp.517-525
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• 2001

Six renaturable protein kinases that utilize the myelin basic protein (MBP) as a substrate were activated during prolonged exposure of cardiac myocytes to okadaic acid (OA). We characterized the substrate preference and activation of these kinases, with particular emphasis on 3 novel kinases-MBPK-55, MBPK-62 and MBPK-87. The transcription factors c-Jun, Elk, ATF2, and c-Fos that are used to assess mitogen-activated protein kinase activation were all poor substrates for these three kinases. MAPKAPK2 was also not phosphorylated. In contrast, Histone IIIS was phosphorylated by MBPK-55 and MBPK-62. These protein kinases were activated in cultured cardiac fibroblasts, H9c2 cardiac myoblasts, and Cos cells. High concentrations (0.5 to $1\;{\mu}M$) of OA were essential for the activation of the protein kinases in all of the cell types examined, whereas calyculin A [an inhibitor of protein phosphatase 1 (PP1) and PP2A], cyclosporin A (a PP2B inhibitor), and an inactive OA analog all failed to activate these kinases. The high dose of okadaic acid that is required for kinase activation was also required for phosphatase inhibition, as assessed by immunoblotting whole cell lysates with anti-phosphothreonine antibodies. A variety of chemical inhibitors, including PD98059 (MEK-specific), genistein (tyrosine kinase-specific) and Bisindolylmaleimide I (protein kinase C-specific), failed to inhibit the OA activation of these kinases. Thus, MBPK-55 and MBPK-62 are also Histone IIIS kinases that are widely expressed and specifically activated upon exposure to high OA concentrations.

• 한국자원식물학회지
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• 제32권6호
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• pp.633-643
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• 2019

Long-term ultraviolet (UV) exposure accelerates the phenomenon of skin photo-aging by activating collagenase and elastase. In this study, we aimed to investigate the effects of a combination of grapefruit and rosemary extracts (cG&Re) on UVB-irradiated damage in HaCaT cells and dorsal mouse skin. In HaCaT cells, cG&Re recovered UVB-reduced cell viability and inhibited protein expression of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (p-Erk), c-Jun N-terminal kinases (p-JNK), and a class of MAPKs (p-P38). Also, cG&Re suppressed UVB-induced collagen and elastin degradation by decreasing matrix metalloproteinases (MMPs) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) expression, which is a transcription factor. Similar results were observed in dorsal mouse skin. Taken together, our data indicate that cG&Re prevent UVB-induced skin photo-aging due to collagen/elastin degradation via activation of MAPKs, MMPs, and the NF-κB signaling pathway in vitro and in vivo.

• Nutrition Research and Practice
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• 제11권5호
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• pp.357-364
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• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제6권3호
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• pp.155-160
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• 2002

It is not known whether gender differences play a role in susceptibility to ischemic acute renal failure. Thus, we examined if there were any differences in susceptibility between male and female mice to kidney ischemic injury, and if so, whether it is due to differences in mitogen activated protein kinases (MAPKs) or inflammatory responses to ischemia. Female mice were protected against kidney ischemia when compared with males. Thirty minutes of bilateral ischemia resulted in marked functional and morphological damages in males, but not in females. The ischemia-induced phosphorylation of c-jun N-terminal stress-activated protein kinases (JNKs) was higher in males than in females. Phosphorylation of extracellular signal-regulated kinases (ERKs) was lower in males than in females. Post- ischemia medullary infiltration of RAW 264.7 cell, a monocyte-macrophage cell, and intercellular adhesion molecule-1 (ICAM-1) were greater in males than in females. In conclusion, males were much more susceptible to ischemia than females. The enhanced propensity to ischemic injury in males was correlated with greater activation of JNKs, greater expression of ICAM-1, and greater trapping of leukocytes in the medulla.

• Archives of Pharmacal Research
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• 제23권6호
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• pp.605-612
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• 2000

Green tea polyphenols (GTP) have been demonstrated to suppress tumorigenesis in several chemical-induced animal carcinogenesis models, and predicted as promising chemopreventive agents in human. Recent studies of GTP extracts showed the involvement of mitogen-activated protein kinases (MAPKs) in the regulation of Phase II enzymes gene expression and induction of apoptosis. In the current work we compared the biological actions of five green tea catechins: (1) induction of ARE reporter gene, (2) activation of MAP kinases, (3) cytotoxicity in human hepatoma HepG2-C8 cells, and (4) caspase activation in human cervical squamous carcinoma HeLa cells. For the induction of phase IIgene assay, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) potently induced antioxidant response element (ARE)-mediated luciferase activity, with induction observed at 25 $\mu\textrm{m}$with EGCG. The induction of ARE reporter gene appears to be structurally related to the 3-gallate group. Comparing the activation of MAPK by the five polyphenols, only EGCG showed potent activation of all three MAPKs (ERK, JNK and p38) in a dose- and time-dependent manner, whereas EGC activated ERK and p38. In the concentration range of 25 $\mu\textrm{m}$ to 1 mM, EGCG and ECG strongly suppressed HepG2-ARE-C8 cell-growth. To elucidate the mechanisms of green tea polyphenol-induced apoptosis, we measured the activation of an important cell death protein, caspase-3 induced by EGCG, and found that caspase-3 was activated in a dose- and time-dependent manner. Interestingly, the activation of caspase-3 was a relatively late event (peaked at 16 h), whereas activation of MAPKs was much earlier (peaked at 2 h). It is possible, that at low concentrations of EGCG, activation of MAPK leads to ARE-mediated gene expression including phase II detoxifying enzymes. Whereas at higher concentrations of EGCG, sustained activation of MAPKs such as JNK leads to apoptosis. These mechanisms are currently under investigation in our laboratory. As the most abundant catechin in GTP extract, we found that EGCG potently induced ARE-mediated gene expression, activated MAP kinase pathway, stimulated caspase-3 activity, and induced apoptosis. These mechanisms together with others, may contribute to the overall chemopreventive function of EGCG itself as well as the GTP.

• 대한통합의학회지
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• 제11권3호
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• pp.159-169
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• 2023

Purpose : Though other Citrus spp. have reported their anti-inflammatory and antioxidative activities in previous studies, the biological activity of Kiyomi (Citrus unshiu × C. sinensis) has not been reported yet. Therefore, this study attempted to analyze the anti-inflammatory mechanisms of Kiyomi leaf ethanol extract (KLEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : The cytotoxic effect of KLEE in RAW 264.7 cells was determined by WST-1 assay. Bacterial endotoxin, the concentration of nitric oxide (NO) was analyzed by the Griess reaction. In addition, Western blot analysis was applied to measure the protein expression level of inducible NO synthase (iNOS). The phosphorylated status of the critical inflammatory transcription factor, nuclear factor (NF)-𝜅B, and its upstream signaling molecules, phosphoinositide 3-kinase (PI3K)/Akt as well as mitogen-activated protein kinases (MAPKs), were also measured by Western blot analysis. Results : KLEE was not cytotoxic up to a concentration of 200 ㎍/㎖, and protein expression levels of iNOS and cyclooxygenase (COX)-2, enzymes that counteract NO and prostaglandin (PG) E2 production, were inhibited by KLEE treatment. The phosphorylated status of PI3K/Akt as well as MAPKs including extracellular regulated kinase (ERK), c-jun NH2kinase (JNK), and p38, were significantly attenuated by KLEE treatment in LPS stimulated RAW 264.7 cells. Moreover, one of phase II enzymes, heme oxygenase (HO)-1 which has known for its anti-inflammatory capacity, was strongly induced by KLEE treatment. Conclusion : Consequently, KLEE treatment significantly attenuated the production of NO as well as the expression levels of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-𝜅B, as well as its upstream signaling molecules, PI3K/Akt and MAPKs, were also diminished by KLEE treatment with statistical significance in LPS-stimulated RAW 264.7 cells. These results suggest that KLEE might be a promising candidate for the attenuation of inflammatory disorders.

• 한국축산식품학회지
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• 제44권3호
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• pp.607-619
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• 2024

Probiotics are functional microorganisms that exhibit various biological activities, such as allergic reactions, inflammation, and aging. The aim of this study is to evaluate the effects of Bifidobacterium lactis CBT BL3 (BL) on the amyloid beta (Aβ)-mediated cognitive impairments. Oral administration of live BL to intracerebroventricularly Aβ-injected mice significantly attenuated short- and long-term memory loss estimated using the Y-maze and Morris water maze tests. We found that expression of apoptosisrelated proteins such as caspase-9, caspase-3, and cleaved poly (ADP-ribose) polymerase was significantly elevated in the brain tissues of Aβ-injected mouse brains when compared to that of the control mouse group. Interestingly, these expression levels were significantly decreased in the brain tissue of mice fed BL for 6 wk. In addition, the abnormal over-phosphorylation of mitogen-activated protein kinases (MAPKs) such as ERK1/2, p38 MAPK, and JNK in the brain tissue of intracerebroventricularly Aβ-injected mice was significantly attenuated by oral administration of BL. Taken together, the results indicate that Aβ-induced cognitive impairment may be ameliorated by the oral administration of BL by controlling the activation of MAPKs/apoptosis in the brain. This study strongly suggests that BL can be developed as a functional probiotic to attenuate Aβ-mediated cognitive deficits.

• Journal of Applied Biological Chemistry
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• 제61권4호
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• pp.417-421
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• 2018

자외선은 가시 광선보다 파장이 짧은 전자기파이며, 오존층을 통과하는 자외선이 피부 노화의 주요 원인이다. 피부 조직을 자외선에 만성적으로 노출 시키면 인간 각질 형성 세포에서 Mitogen-activated Protein Kinases (MAPKs) 신호 전달 경로가 활성화되어 매트릭스 metalloproteinases (MMPs) 생성이 증가한다. 본 연구에서는 제주도의 초본 추출물을 대상으로 자외선 자극을 통해 인간 각질 형성 세포(HaCaTs)의 항 노화 효과에 대해 조사 하였다. 우리는 자외선 유도 된 각질 형성 세포에서 MMP-1 유전자와 단백질 발현 수준을 측정 하였으며 그 결과, Thymus quinquecostatus 추출물(TQE)은 자외선 조사된 HaCaT 세포에서 의해 농도 의존적으로 MMP-1의 발현을 유의하게 감소시키는 것으로 확인되었다. 또한, TQE는 MAPK 신호 전달요소 인 ERK1/2, JNK1/2 및 p38 단백질의 자외선 유도에 따른 인산화를 유의 적으로 감소시켰다. 이러한 결과는 MAPKs 경로가 인간 각질 세포에서 UV 유도 MMP-1 생산에 대한 TQE의 억제 효과에 기여할 수 있음을 시사한다. 우리의 결과는 아마도 인간 각질형성 세포에서 TQE가 자외선 유도된 MMP-1 생산을 억제하는 피부 노화 소재로 활용될 수 있음을 시사한다.