• Molecules and Cells
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• v.28 no.5
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• pp.417-422
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• 2009

Mitogen activated protein kinase (MAPK) are known to get activated during various stress signals and transduce the message from the cell membrane to the nucleus for appropriate cellular reorganization. Though, a certain basal activity of MAPK is often observed in the control plants. Prolonged exposure of rice plants to lowered or elevated temperature exhibited a rhythm in the activation of MAPKs. We analyzed existence of a possible endogenous rhythm in the activity of MAPKs in rice plants. The plants growing at constant temperature entrained in 16/8 h day-night cycle showed diurnal rhythm in activity. When the activation of MAPK was tested under continuous conditions by shifting plants to continuous darkness for a period of 72 h, the periodic rhythm persisted and followed a circadian pattern. Analysis of the transcripts of group A, B and C members of MAPKs under above conditions by quantitative real time PCR revealed that the members of group C exhibit periodic rhythm. Our data indicates that the MAP kinase activity in rice follows rhythmic expression in a circadian manner.

• Development and Reproduction
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• v.6 no.1
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• pp.1-6
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• 2002

To elucidate the mechanism underlying the embryotropic effect of extracellular matrix(ECM) on the preimplantation development of mammalian embryos, the involvement of mitogen-activated protein kinase(MAPK) downstream the integrin signaling was examined in mouse blastocysts. Blastocysts were cultured in the presence of growth factor-reduced(GFR) Matrigel(0.5％, v/v). MAPK activity was measured by in vitro phosphorylation of myelin basic protein by the Erk1/2 antibody immunoprecipitates of embryonic extract following the Matrigei treatment. MAPK activity of the early blastocysts rapidly increased within 10 min fo1lowing the Matrigel treatment. When the embryos were cultured for 12 h in the presence of Matrigel, the MAPK activity was significantly higher than that ot the control embryos. PD098059, a MAPK kinase(MEK) inhibitor, attenuated the effect of Matrigel on the change in MAPK activity. Taken together, it suggested that the embryotropic effect of ECM proteins might be mediated by the activation of MAPK cascade.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.169-178
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• 2020

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl-2 family and MAPK/Akt signaling pathways.

• Journal of Plant Biotechnology
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• v.49 no.4
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• pp.300-306
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• 2022

The mitogen-activated protein kinase (MAPK) signaling cascade is essential for a wide range of cellular responses in plants, including defense responses, responses to abiotic stress, hormone signaling, and developmental processes. Recent investigations have shown that the stress, ethylene, and MAPK signaling pathways negatively affect the formation of nitrogen-fixing nodules by directly modulating the symbiotic signaling components. However, the molecular mechanisms underlying the defense responses mediated by MAPK signaling in the organogenesis of nitrogen-fixing nodules remain unclear. In the present study, I demonstrate that the Medicago truncatula mitogen-activated protein kinase kinase 5 (MtMKK5)-Medicago truncatula mitogen-activated protein kinase 3/6 (MtMPK3/6) signaling module, expressed specifically in the symbiotic nodules, promotes defense signaling, but not ethylene signaling pathways, thereby inhibiting nodule development in M. truncatula. U0126 treatment resulted in increased cell division in the nodule meristem zone due to the inhibition of MAPK signaling. The phosphorylated TEY motif in the activation domain of MtMPK3/6 was the target domain associated with specific interactions with MtMKK5. I have confirmed the physical interactions between M. truncatula nodule inception (MtNIN) and MtMPK3/6. In the presence of high expression levels of the defense-related genes FRK1 and WRKY29, MtMKK5a overexpression significantly enhanced the defense responses of Arabidopsis against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Overall, my data show that the negative regulation of symbiotic nitrogen-fixing nodule organogenesis by defense signaling pathways is mediated by the MtMKK5-MtMPK3/6 module.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.282-290
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• 2019

Background: Ginsenoside Rg3 (G-Rg3) is the major bioactive ingredient of Panax ginseng and has many pharmacological effects, including antiadipogenic, antiviral, and anticancer effects. However, the effect of G-Rg3 on mast cell-mediated allergic inflammation has not been investigated. Method: The antiallergic effects of G-Rg3 on allergic inflammation were evaluated using the human and rat mast cell lines HMC-1 and RBL-2H3. Antiallergic effects of G-Rg3 were detected by measuring cyclic adenosine monophosphate (cAMP), detecting calcium influx, and using real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and in vivo experiments. Results: G-Rg3 decreased histamine release from activated mast cells by enhancing cAMP levels and calcium influx. Proinflammatory cytokine production was suppressed by G-Rg3 treatment via regulation of the mitogen-activated protein kinases/nuclear factor-kappa B and receptor-interacting protein kinase 2 (RIP2)/caspase-1 signaling pathway in mast cells. Moreover, G-Rg3 protected mice against the IgE-mediated passive cutaneous anaphylaxis reaction and compound 48/80-induced anaphylactic shock. Conclusion: G-Rg3 may serve as an alternative therapeutic agent for improving allergic inflammatory disorders.

• The Plant Pathology Journal
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• v.24 no.4
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• pp.375-383
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• 2008

It is well known that NtMEK2, a tobacco MAPK kinase, is the upstream kinase of both salicylic acid-induced protein kinase and wound-induced protein kinase. In addition, expression of $NtMEK2^{DD}$, a constitutively active mutant of NtMEK2, is known to induce multiple defense responses in tobacco. In this study, transgenic rice plants that contained an active or inactive mutant of NtMEK2 under the control of a steroid inducible promoter were generated and used to determine if a similar MAPK cascade is involved in disease resistance in rice. The expression of $NtMEK2^{DD}$ in transgenic rice plants resulted in HR-like cell death. The observed cell death was preceded by the activation of endogenous rice 48-kDa MBP kinase, which is also activated by Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice. In addition, prolonged activation of the MAPK induced the generation of hydrogen peroxide and up-regulated the expression of defense-related genes including the pathogenesis-related genes, peroxidases and glutathione S-transferases. These results demonstrate that NtMEK2 is functionally replaceable with rice MAPK kinase in inducing the activation of the downstream MAPK, which in turn induces multiple defense responses in rice.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.436-446
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• 2018

Background: The potential therapeutic values of Korean Red Ginseng extract (KRGE) in autoimmune disorders of nervous system have not been fully investigated. Methods: We used an acute experimental autoimmune encephalomyelitis animal model of multiple sclerosis and determined the effects and mechanism of KRGE on spinal myelination. Results: Pretreatment with KRGE (100 mg/kg, orally) for 10 days before immunization with myelin basic protein $(MBP)_{68-82}$ peptide exerted a protective effect against demyelination in the spinal cord, with inhibited recruitment and activation of immune cells including microglia, decreased mRNA expression of detrimental inflammatory mediators (interleukin-6, interferon-${\gamma}$, and cyclooxygenase-2), but increased mRNA expression of protective inflammatory mediators (insulin-like growth factor ${\beta}1$, transforming growth factor ${\beta}$, and vascular endothelial growth factor-1). These results were associated with significant downregulation of p38 mitogen-activated protein kinase and nuclear factor-${\kappa}B$ signaling pathways in microglia/macrophages, T cells, and astrocytes. Conclusion: Our findings suggest that KRGE alleviates spinal demyelination in acute experimental autoimmune encephalomyelitis through inhibiting the activation of the p38 mitogen-activated protein kinase/nuclear factor-${\kappa}B$ signaling pathway. Therefore, KRGE might be used as a new therapeutic for autoimmune disorders such as multiple sclerosis, although further investigation is needed.

• Journal of Korean Neurosurgical Society
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• v.56 no.1
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• pp.1-4
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• 2014

Objective : The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs. Methods : We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun $NH_2$-terminal kinases (JNKs) and ${\beta}$-actin as the control group. Results : Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, $1{\mu}M$) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and $1{\mu}M$, p<0.05). Conclusion : Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations.

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

• BMB Reports
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• v.47 no.12
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• pp.685-690
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• 2014

The Ras/Raf/MEK/Erk signaling pathway is important for regulation of cell growth, proliferation, differentiation, survival, and apoptosis in response to a variety of extracellular stimuli. Lack of Erk MAPK activation is observed in several cancer cells despite active activation of Ras. However, little is known about the modulation of Erk1/2 activity by active Ras. Here, we show that overexpression of active H-Ras (H-RasG12R) in NIH3T3 fibroblasts impaired FGF2-induced Erk1/2 phosphorylation, as compared to wild-type cells. Northern blot analysis revealed that prolonged expression of active Ras increased MAP kinase phosphatase 3 (MKP3) mRNA expression, a negative regulator of Erk MAPK. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway abrogated active Ras-induced up-regulation of MKP3 expression, leading to the rescue of Erk1/2 phosphorylation. Our results demonstrated that the Ras/Raf/MEK/Erk signaling cascade is negatively regulated by the PI3K/Aktdependent transcriptional activation of the MKP3 gene.