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

• Journal of Korean Neurosurgical Society
• /
• 제56권1호
• /
• pp.1-4
• /
• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권4호
• /
• pp.365-374
• /
• 2021

The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model. We also examined whether the glial cell expression and phosphorylated p38 (p-p38) mitogen-activated protein kinases (MAPKs) in the TNC are affected by rapamycin. Mice were intraperitoneally given rapamycin (0.1, 0.3, or 1.0 mg/kg); then, 30 min after, 5% formalin (10 μl) was subcutaneously injected into the right upper lip. The rubbing responses with the ipsilateral forepaw or hindpaw were counted for 45 min. High-dose rapamycin (1.0 mg/kg) produced significant antinociceptive effects in both the first and second phases of formalin test. The number of Fos-ir cells in the ipsilateral TNC was also reduced by high-dose rapamycin compared with vehicle-treated animals. Furthermore, the number of p-p38-ir cells the in ipsilateral TNC was significantly decreased in animals treated with high-dose rapamycin; p-p38 expression was co-localized in microglia, but not neurons and astrocytes. Therefore, the mTOR inhibitor, rapamycin, reduces orofacial nociception and Fos expression in the TNC, and its antinociceptive action on orofacial pain may be associated with the inhibition of p-p38 MAPK in the microglia.

• Tuberculosis and Respiratory Diseases
• /
• 제53권6호
• /
• pp.595-611
• /
• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• 대한본초학회지
• /
• 제22권2호
• /
• pp.147-153
• /
• 2007

Objectives : Sophora flavescens (SF) is widely used in traditional herbal medicine in Korea and is well recognized for its anti-inflammatory effect. However, its effect on Tumornecrosis factor alpha (Tnf) production in BV2 microglial cell is not yet known. Methods : We investigated the effect of SF on the production and expression of Tnf, a well known inflammatory mediator, in lipopolysaccaride (LPS)-activated BV2 microglial cells. Results : The LPS-induced Tnf production was markedly reduced by treatment with SF (50 ${\mu}g/ml$). In reverse transcription polymerase chain reaction (RT-PCR) analysis, SF suppressed the LPS activated expression of Tnf mRNA. In addition, Western blot analysis confirmed that SF suppressed the expression of Tnf. Sophora flavescens also inhibited the LPS-induced phosphylation of extracellular signal-regulated kinases (ERK), which mediate the Tnfproduction signaling pathway whereas LPS-induced phosphylation of p38 mitogen activated protein kinase (p38 MAPK), and c-Jun NH2-terminal kinases (JNK) was not inhibited by SF, which implies that SF suppresses LPS-induced Tnf production via the ERK mediated pathway. Conclusion : Taken together, these findings indicated that SF inhibits LPS-induce Tnf production, and that this inhibitory effect is mediated via the ERK pathway.

• Journal of Ginseng Research
• /
• 제40권3호
• /
• pp.285-291
• /
• 2016

Background: Ginsenosides have been shown to exert beneficial pharmacological effects on the central nervous, cardiovascular, and endocrine systems. We sought to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced pulmonary hypertension and to elucidate the underlying mechanism. Methods: MCT-intoxicated rats were treated with gradient doses of TG, with or without $N^G$-nitro-$\small{L}$-arginine methyl ester. The levels of molecules involving the regulation of nitric oxide and mitogen-activated protein kinase pathways were determined. Results: TG ameliorated MCT-induced pulmonary hypertension in a dose-dependent manner, as assessed by the right ventricular systolic pressure, the right ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG increased the levels of pulmonary nitric oxide, endothelial nitric oxide synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen-activated protein kinase phosphatase-1 expression and promoted the dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2. Conclusion: TG attenuates MCT-induced pulmonary hypertension, which may involve in part the regulation of nitric oxide and mitogen-activated protein kinase pathways.

• The Journal of Korean Physical Therapy
• /
• 제20권3호
• /
• pp.53-59
• /
• 2008

Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.

• 대한한의학회지
• /
• 제39권4호
• /
• pp.158-170
• /
• 2018

Objectives: The objective of this study is Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) and bee venom (BV) to experimental prove comparative study of VCA and BV on the anti-cancer effect and mechanisms of action. Methods: In this study, it was examined in a human hepatocellular carcinoma cell line, Hep G2 cells. Cytotoxic effects of VCA and BV on Hep G2 cells were determined by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay in vitro. VCA and BV killed Hep G2 cells in a time- and dose-dependent manner. Results: The apoptotic cell death was then confirmed by propidium iodide staining and DNA fragmentation analysis. The mechanisms of action was examined by the expression of anti-apoptotic proteins and activation of mitogen-activated protein kinases. Treatment of Hep G2 cells with VCA activated poly (ADP-ribose) polymerase-1 (PARP-1) known as a marker of apoptosis, and mitogen-activated protein kinases signaling pathways including SAPK/JNK, MAPK and p38. BV also activated PARP-1, MAPK, p38 but not JNK. The expression level of anti-apoptotic molecule, Bcl-X, was decreased by VCA treatment but not BV. Finally, the phosphorylation level of ERM proteins involved in the cytoskeleton homeostasis was decreased by both stimuli. Conclusion: We examined the involvement of kinase in VCA or BV - induced apoptosis by using kinase inhibitors. VCA-induced apoptosis was partially inhibited by in the presence.

• 한국자원식물학회지
• /
• 제32권6호
• /
• pp.633-643
• /
• 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
• /
• 제11권5호
• /
• 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.