• Title/Summary/Keyword: ATF

Search Result 201, Processing Time 0.021 seconds

Anti-inflammatory effect of Lonicera caerulea through ATF3 and Nrf2/HO-1 Activation in LPS-stimulated RAW264.7 Cells

  • Kim, Ha Na;Park, Su Bin;Kim, Jeong Dong;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
    • /
    • 2019.10a
    • /
    • pp.65-65
    • /
    • 2019
  • In this study, we evaluated the anti-inflammatory effect of extracts of leaves (LCLE) and branches (LCBE) from L. caerulea in LPS-stimulated RAW264.7 cells. Inhibitory effect of LCLE and LCBE against LPS-induced overproduction of NO, iNOS and $IL-1{\beta}$ was higher than LCFE. Furthermore, LCLE and LCBE significantly inhibited the overexpression of COX-2, IL-6 and $TNF-{\alpha}$ in LPS-stimulated RAW264.7 cells. LCLE and LCBE did not inhibited LPS-induced degradation of $I{\kappa}B-{\alpha}$, but blocked the nuclear accumulation of p65. LCLE did not inhibited LPS-induced phosphorylation of ERK1/2 and p38, while LCBE significantly attenuated phosphorylation level of p38. LCLE and LCBE increased HO-1 protein level and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by HO-1 knockdown. The inhibition of p38 by SB203580 and ROS by NAC blocked HO-1 expression by LCLE and LCBE. LCLE and LCBE increased p38 phosphorylation and the inhibition of ROS by NAC blocked p38 phosphorylation LCLE and LCBE. LCLE and LCBE induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 and ROS. In addition, LCLE and LCBE increased ATF3 expression and decrease of iNOS and $IL-1{\beta}$ expression by LCLE and LCBE was inhibited by ATF3 knockdown. Collectively, LCLE and LCBE inhibited LPS-induced $NF-{\kappa}B$ activation by blocking p65 nuclear accumulation, increased HO-1 expression by ROS/p38/Nrf2 activation, and increased ATF3 expression. Furthermore, LCBE inhibited LPS-induced p38 phosphorylation.

  • PDF

An evaluation on in-pile behaviors of SiCf/SiC cladding under normal and accident conditions with updated FROBA-ATF code

  • Chen, Ping;Qiu, Bowen;Li, Yuanming;Wu, Yingwei;Hui, Yongbo;Deng, Yangbin;Zhang, Kun
    • Nuclear Engineering and Technology
    • /
    • v.53 no.4
    • /
    • pp.1236-1249
    • /
    • 2021
  • Although there are still controversial opinions and uncertainty on application of SiCf/SiC composite cladding as next-generation cladding material for its great oxidation resistance in high temperature steam environment and other outstanding advantages, it cannot deny that SiCf/SiC cladding is a potential accident tolerant fuel (ATF) cladding with high research priority and still in the engineering design stage for now. However, considering its disadvantages, such as low irradiated thermal conductivity, ductility that barely not exist, further evaluations of its in-pile behaviors are still necessary. Based on the self-developed code we recently updated, relevant thermohydraulic and mechanical models in FROBA-ATF were applied to simulate the cladding behaviors under normal and accident conditions in this paper. Even through steady-state performance analysis revealed that this kind of cladding material could greatly reduce the oxidation thickness, the thermal performance of UO2-SiC was poor due to its low inpile thermal conductivity and creep rate. Besides, the risk of failure exists when reactor power decreased. With geometry optimization and dopant addition in pellets, the steady-state performance of UO2-SiC was enhanced and the failure risk was reduced. The thermal and mechanical performance of the improved UO2-SiC was further evaluated under Loss of coolant accident (LOCA) and Reactivity Initiated Accident (RIA) conditions. Transient results showed that the optimized ATF had better thermal performance, lower cladding hoop stress, and could provide more coping time under accident conditions.

Anti-Inflammatory Activity of Acacia Honey through Inhibition of NF-κB and MAPK/ATF2 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

  • Kim, Ha Na;Son, Kun Ho;Jeong, Hyung Jin;Park, Su Bin;Kim, Jeong Dong;Jeong, Jin Boo
    • Korean Journal of Plant Resources
    • /
    • v.31 no.6
    • /
    • pp.612-621
    • /
    • 2018
  • Honey used as conventional medicine has various pharmacological properties. In the honey and anti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However, the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, we investigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuated NO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased the expressions of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatory chemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated $I{\kappa}B$-${\alpha}$ degradation and subsequent nuclear accumulation of p65, which resulted in the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. AH dose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AH significantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators such as NO, iNOS, $TNF-{\alpha}$, IL-6, $IL-1{\beta}$ and MCP-1 via interruption of the $NF-{\kappa}B$ and MAPK/ATF2 signaling pathways.

Laminar Flow Inhibits ER Stress-Induced Endothelial Apoptosis through PI3K/Akt-Dependent Signaling Pathway

  • Kim, Suji;Woo, Chang-Hoon
    • Molecules and Cells
    • /
    • v.41 no.11
    • /
    • pp.964-970
    • /
    • 2018
  • Atherosclerosis preferentially involves in prone area of low and disturbed blood flow while steady and high levels of laminar blood flow are relatively protected from atherosclerosis. Disturbed flow induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). ER stress is caused under stress that disturbs the processing and folding of proteins resulting in the accumulation of misfolded proteins in the ER and activation of the UPR. Prolonged or severe UPR leads to activate apoptotic signaling. Recent studies have indicated that disturbed flow significantly up-regulated $p-ATF6{\alpha}$, $p-IRE1{\alpha}$, and its target spliced XBP-1. However, the role of laminar flow in ER stress-mediated endothelial apoptosis has not been reported yet. The present study thus investigated the role of laminar flow in ER stress-dependent endothelial cell death. The results demonstrated that laminar flow protects ER stress-induced cleavage forms of PARP-1 and caspase-3. Also, laminar flow inhibits ER stress-induced $p-eIF2{\alpha}$, ATF4, CHOP, spliced XBP-1, ATF6 and JNK pathway; these effects are abrogated by pharmacological inhibition of PI3K with wortmannin. Finally, nitric oxide affects thapsigargin-induced cell death in response to laminar flow but not UPR. Taken together, these findings indicate that laminar flow inhibits UPR and ER stress-induced endothelial cell death via PI3K/Akt pathway.

Potentiation of Anticancer Effect of Artesunate by Combination with Nonsteroidal Anti-inflammatory Drugs on Human Cancer Cells (Artesunate와 비스테로이드소염제 NSAID의 병용 처리에 의한 항암 활성 증강)

  • Moon, Hyun-Jung;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
    • /
    • v.31 no.10
    • /
    • pp.873-884
    • /
    • 2021
  • The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

FMDV 2C Protein of Foot-and-mouth Disease Virus Increases Expression of Pro-inflammatory Cytokine TNFα via Endoplasmic Reticulum Stress (구제역바이러스의 FMDV 2C 단백질은 소포체 스트레스를 통해서 염증 유도 사이토카인 TNFα의 발현을 증가시킴)

  • Kang, Hyo Rin;Seong, Mi So;Nah, Jin Ju;Ryoo, Soyoon;Ku, Bok Kyung;Cheong, JaeHun
    • Journal of Life Science
    • /
    • v.30 no.3
    • /
    • pp.285-290
    • /
    • 2020
  • Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

A Study for Effects of Automatic Transmission Fluid on Fuel Economy (자동변속기유가 연비에 미치는 영향에 대한 연구)

  • Cha SangYeob;Yang SiWon
    • Proceedings of the Korean Society of Tribologists and Lubrication Engineers Conference
    • /
    • 2004.11a
    • /
    • pp.117-122
    • /
    • 2004
  • In order to improve the fuel economy by design change of automatic transmission, various technologies such as increased shift stages, slip control of lock-up clutch and compact and low-weight design have been developed. And also many OEMs have developed their own ATFs as a part of these automatic transmissions. In this study. to investigate the effects of ATF characteristics on fuel economy, we got the worldwide OEM ATFs and made some reference fluids. And physical properties, frictional characteristics and fuel economy using dynamometer test for these fluids were evaluated. From the investigation, it was found that viscosities of ATFs are correlated with fuel economy in dynamometer test and reducing the viscosities made it possible to obtain fuel economy.

  • PDF

Structure Optimization of Fuzzy Neural Network by Genetic Algorithm

  • Fukuda, Toshio;Ishigame, Hideyuki;Shibata, Takanori;Arai, Fumihito
    • Proceedings of the Korean Institute of Intelligent Systems Conference
    • /
    • 1993.06a
    • /
    • pp.964-967
    • /
    • 1993
  • This paper presents an auto tuning method of fuzzy inference using Genetic Algorithm. The determination of membership functions by human experts is a difficult problem. Therefore, some auto-tuning methods have been proposed to reduce the time-consuming operations. However, the convergence of the tuning by the previous methods depends on the initial conditions of the fuzzy model. So, we proposes an auto tuning method for the fuzzy neural network by Genetic Algorithm (ATF system). This paper shows effectiveness of the ATF system by simulations.

  • PDF