• Title/Summary/Keyword: N signaling

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Ethyl Acetate Fraction from Petasites japonicus Attenuates Oxidative Stress through Regulation of Nuclear Factor E2-Related Factor-2 Signal Pathway in LLC-PK1 Cells (머위 에틸아세테이트 분획물의 LLC-PK1 세포에서의 Nrf-2 매개 항산화 효과)

  • Kim, Ji Hyun;Lee, Jaemin;Lee, Sanghyun;Cho, Eun Ju
    • Korean Journal of Pharmacognosy
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    • v.47 no.1
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    • pp.55-61
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    • 2016
  • Antioxidant effects and nuclear factor E2-related factor-2 (Nrf-2) signal pathway of methanol extract and 4 fractions [n-hexane, methylene chloride, ethyl acetate (EtOAc), and n-butanol fractions] from Petasites japonicus were investigated. The EtOAc fraction showed highest polyphenol and flavonoid contents among other fractions. In addition, EtOAc fraction showed stronger scavenging activity against superoxide anion radical than other fractions. Furthermore, we investigated antioxidants effects of the EtOAc fraction under cellular system using $LLC-PK_1$ cells. The EtOAc fraction dose-dependently increased the antioxidant protein expressions of heme oxygenase 1 (HO-1) and thioredoxin reductase 1 (TrxR1) known to be involved in oxidative stress, through activation of Nrf-2. The treatment of EtOAc fraction ($100{\mu}g/mL$) led to the elevation of the high expression of Nrf-2-dependent factor such as HO-1 and TrxR1. These results indicated that the EtOAc fraction of P. japonicus showed high antioxidant activity by regulation of Nrf-2 signaling pathway.

A Novel Scheme for Efficient Interworking with MIPv6 Hosts in the PMIPv6 Network (PMIPv6 망에서 MIPv6 호스트의 효율적인 연동 방안에 관한 연구)

  • Park, Jong-Won;Min, Sang-Won;Kim, Bok-Ki
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.35 no.3B
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    • pp.373-379
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    • 2010
  • In this paper, we propose a novel MAS algorithm to reduce the amount of signaling and data traffics. To notify an MIPv6 host of the proposed operation, we design a new binding registration function into the MAG, and suggest the modified RS and RA messages. The binding registration in the MAG instead of the LMA is accomplished to support the PMIPv6, whereas a 1-bit N flag in the RS and RA message indicates where the MAG supports the PMIPv6 or not. Our proposed algorithm has the advantage for MIPv6 hosts in the PMIPv6 network in the viewpoints of network utilization and performance. To show the verification and better performance of the MAS algorithm, we evaluate the amount of traffic and its related performance, and compares those with performance of the normal PMIPv6. These results show that our proposed algorithm can operate efficiently and give better performance for MIPv6 hosts in the PMIPv6 network.

Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase

  • Jeong, Yong-Tae;Song, Chi-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.21 no.9
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    • pp.921-929
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    • 2011
  • Stimulation of AMP-activated protein kinase (AMPK) signaling followed by increase of glucose uptake in L6 myotubes were studied with organic solvent extract of Malva verticillata (MV) seeds. Ethanol extract of M. verticillata seeds (MVE) significantly increased the phosphorylation level of AMPK, acetyl-CoA carboxylase (ACC), and glucose uptake in L6 myotube cells. The MVE was fractionated with n-hexane (MVE-H), chloroform (MVE-C), ethylacetate (MVE-E), n-butanol (MVE-B), and water (MVE-W). MVE-H (150 ${\mu}g$/ml) showed the highest phosphorylating activity and increased glucose uptake by 2.3-fold. Oral administration of MVE-H (40 mg/kg) for 4 weeks to type 2 diabetic (db/db) mice reduced non-fasting and fasting blood glucose levels by 17.1% and 23.3%, respectively. Phosphorylation levels of AMPK and ACC in the soleus muscle and liver tissue of db/db mice were significantly increased by the administration of MVE-H. MVE-H was further fractionated using preparative HPLC to identify the AMPK-activating compounds. The NMR and GC-MS analyses revealed that ${\beta}$-sitosterol was a major effective compound in MVE-H. Phosphorylation levels of AMPK and ACC, and glucose uptake were significantly increased by the treatment of MVE-S (${\beta}$-sitosterol) isolated from M. verticillata to L6 cells, and these effects were attenuated by an AMPK inhibitor (Compound C) pretreatment. These results, taken together, demonstrate that increased glucose uptake in L6 myotubes by MVE-H treatment is mainly accomplished through the activation of AMPK. Our finding suggests that the extract isolated from M. verticillata seed would be beneficial for the treatment of metabolic disease including type 2 diabetes and hyperlipidemia.

Ginsenosides from Korean Red Ginseng ameliorate lung inflammatory responses: inhibition of the MAPKs/NF-κB/c-Fos pathways

  • Lee, Ju Hee;Min, Dong Suk;Lee, Chan Woo;Song, Kwang Ho;Kim, Yeong Shik;Kim, Hyun Pyo
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.476-484
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    • 2018
  • Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.

Effects of Reactive Oxygen Species and Nitrogen Species on the Excitability of Spinal Substantia Gelatinosa Neurons

  • Park, Joo Young;Park, Areum;Chun, Sang Woo
    • International Journal of Oral Biology
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    • v.41 no.3
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    • pp.141-147
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    • 2016
  • Reactive oxygen species (ROS) and nitrogen species (RNS) are both important signaling molecules involved in pain transmission in the dorsal horn of the spinal cord. Xanthine oxidase (XO) is a well-known enzyme for the generation of superoxide anions ($O_2^{\bullet-}$), while S-nitroso-N-acetyl-DL-penicillamine (SNAP) is a representative nitric oxide (NO) donor. In this study, we used patch clamp recording in spinal slices of rats to investigate the effects of $O_2^{\bullet-}$ and NO on the excitability of substantia gelatinosa (SG) neurons. We also used confocal scanning laser microscopy to measure XO- and SNAP-induced ROS and RNS production in live slices. We observed that the ROS level increased during the perfusion of xanthine and xanthine oxidase (X/XO) compound and SNAP after the loading of 2',7'-dichlorofluorescin diacetate ($H_2DCF-DA$), which is an indicator of intracellular ROS and RNS. Application of ROS donors such as X/XO, ${\beta}-nicotinamide$ adenine dinucleotide phosphate (NADPH), and 3-morpholinosydnomimine (SIN-1) induced a membrane depolarization and inward currents. SNAP, an RNS donor, also induced membrane depolarization and inward currents. X/XO-induced inward currents were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger) and manganese(III) tetrakis(4-benzoic acid) porphyrin (MnTBAP; superoxide dismutase mimetics). Nitro-L-arginine methyl ester (NAME; NO scavenger) also slightly decreased X/XO-induced inward currents, suggesting that X/XO-induced responses can be involved in the generation of peroxynitrite ($ONOO^-$). Our data suggest that elevated ROS, especially $O_2^{\bullet-}$, NO and $ONOO^-$, in the spinal cord can increase the excitability of the SG neurons related to pain transmission.

The Effects of Acupuncture at GB34 on Disuse Muscle Atrophy in Rats (흰쥐의 불용성 근위축에 양릉천 자침이 미치는 효과)

  • Kim, Bum Hoi
    • Journal of Korean Medicine Rehabilitation
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    • v.28 no.4
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    • pp.1-9
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    • 2018
  • Objectives Disuse muscle atrophy occurs in response to pathologies such as joint immobilization, inactivity or bed rest. Muscle disuse is accompanied by an increase in apoptotic signaling, which mediates some of the responses to unloading in the muscle. GB34 (Yanglingquan) is a acupuncture point on the lower leg and one of the most frequently used points in various skeletomuscular diseases. In this study, the hypothesis that the acupuncture at GB34 could attenuate immobilization-induced skeletal muscle atrophy was tested. Methods The left hindlimb immobilization was performed with casting tape in both GB34 group (n=10) and Control group (n=10). The rats in GB34 group were daily treated with acupuncture at GB34. After 2 weeks of immobilization, the morphology of right and left gastrocnemius muscles in both GB34 and Control groups were assessed by hematoxylin and eosin staining. To investigate the immobilization-induced muscular apoptosis, the immunohistochemical analysis of Bax and Bcl-2 was carried out. Results GB34 group represented the significant protective effects against the reductions of the left gastrocnemius muscles weight and average cross section area to compared with Control group. The acupuncture at GB34 significantly reduced the immunoreactivity of BAX and increased the immunoreactivity of Bcl-2 in gastrocnemius muscle compared with Control group. Conclusions These results suggest that the acupuncture at GB34 has protective effects against immobilization-induced muscle atrophy by regulating the activities of apoptosis-associated BAX/Bcl-2 proteins in gastrocnemius muscle.

Design and Performance Analysis of Cost-Effective and Fast Inter-Domain NEMO Scheme with Multicasting Support (멀티캐스팅 지원의 비용효과적인 도메인간 빠른 NEMO 기법의 설계 및 성능분석)

  • Han, Sunghee;Jeong, Jongpil
    • KIPS Transactions on Computer and Communication Systems
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    • v.1 no.2
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    • pp.87-98
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    • 2012
  • In recent years, there are many data and multimedia services that are supported by WiFi-enabled mobile devices. As a result, the demand for the ability to connect to the Internet anywhere is rapidly increasing and network infrastructure is becoming increasingly important. The design of cost-efficient network mobility (NEMO) protocol is intended to reduce the demand for limited wired/wireless network bandwidth at the signaling of mobility support and packet delivery operations. In this paper, we propose a cost-effective inter-LMA domain mobility management scheme which provides fast handover with multicasting support in NEMO environments. And our Fast PR-NEMO scheme is compared with N-PMIPv6, rNEMO, and PR-NEMO. In conclusion, our proposed scheme shows the best performance in terms of location updating cost, and packet tunneling cost.

Anti-inflammatory and anti-diabetic effects of brown seaweeds in high-fat diet-induced obese mice

  • Oh, Ji-Hyun;Kim, Jaehoon;Lee, Yunkyoung
    • Nutrition Research and Practice
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    • v.10 no.1
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    • pp.42-48
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    • 2016
  • BACKGROUND/OBJECTIVES: Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS: Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS: Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-$1{\beta}$ and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION: Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells.

Development of a Reporter System Monitoring Regulated Intramembrane Proteolysis of the Transmembrane bZIP Transcription Factor ATF6α

  • Kim, Jin-Ik;Kaufman, Randal J.;Back, Sung Hoon;Moon, Ja-Young
    • Molecules and Cells
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    • v.42 no.11
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    • pp.783-793
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    • 2019
  • When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of $ATF6{\alpha}$ by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human $ATF6{\alpha}$ N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-$hATF6{\alpha}$ deletion variant was cleaved to liberate active transcription activator encompassing GV-$hATF6{\alpha}$ fragment which could translocate into the nucleus. The translocated GV-$hATF6{\alpha}$ fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-$hATF6{\alpha}$(333) represents an innovative tool to investigate regulated intramembrane proteolysis of $ATF6{\alpha}$. It can substitute active pATF6(N) binding motif-based reporter cell lines.

Avenanthramide C as a novel candidate to alleviate osteoarthritic pathogenesis

  • Tran, Thanh-Tam;Song, Won-Hyun;Lee, Gyuseok;Kim, Hyung Seok;Park, Daeho;Huh, Yun Hyun;Ryu, Je-Hwang
    • BMB Reports
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    • v.54 no.10
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    • pp.528-533
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    • 2021
  • Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.