• 동의생리병리학회지
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• 제28권1호
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• pp.63-68
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• 2014

The fruit of Tribulus terrestris L. (Zygophyllaceae) is an important source of traditional Korean and Chinese medicines. In this study, NNMBS223, consisting of the ethanol extract of T. terrestris, showed potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS223 in suppressing the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and production of iNOS-derived nitric oxide (NO), COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages. In addition, NNMBS223 induced expression of heme oxygenase (HO)-1 through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of NNMBS223 on LPS-induced production of NO and PGE2 were partially reversed by the HO activity inhibitor tin protoporphyrin (SnPP). These findings suggest that Nrf2-dependent increases in expression of HO-1 induced by NNMBS223 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

• Journal of Applied Biological Chemistry
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• 제57권3호
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• pp.205-210
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• 2014

Persicaria orientalis (L.) Spach (Po)와 Potentilla fragarioides var. major Maxim (Pf)의 추출물로 reactive oxygen species (ROS)와 같은 free radical의 억제를 통한 항염증 활성을 살펴보았다. 또한, Po와 Pf로 LPS를 처리한 murine macrophage RAW 264.7 세포에서 발생한 nitric oxide의 저해와 NF-${\kappa}B$의 핵으로 translocation의 저해를 살펴보았다. 3-morpholinosydnonimine hydrochloride (SIN-1) $50{\mu}M$에 의해 유도된 ROS의 Po에 의한 50% 저해값 ($IC_{50}$)은 $23.35{\pm}1.27mg/mL$, Pf에 의한 $IC_{50}$은 $8.46{\pm}1.22mg/mL$이었다. 또한, SIN-1 $50{\mu}M$에 의해 유도된 peroxynitrite의 Po에 의한 $IC_{50}$은 $2.19{\pm}0.04mg/mL$, Pf에 의한 $IC_{50}$은 $0.80{\pm}0.02mg/mL$이었다. LPS 1 mg/mL을 처리한 RAW 264.7 세포에서 Nitric oxide는 증가하였으나 Po와 Pf 추출물을 처리한 그룹에서 농도의존적, 유의적으로 감소하였다. Po 추출물을 처리한 그룹의 Nitric oxide 생성량은 $13.34{\pm}0.67{\mu}M$, Pf 추출물을 처리한 그룹의 Nitric oxide 생성량은 $11.45{\pm}0.57{\mu}M$이었다. 또한, Po와 Pf 추출물은 LPS를 처리한 RAW 264.7 세포에서 NF-${\kappa}B$의 핵으로의 translocation을 저해하였다. 그러므로, Po와 Pf는 항염증 소재로서의 가능성이 충분하다고 사료된다.

• Journal of Radiation Protection and Research
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• 제25권1호
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• pp.21-30
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• 2000

벼의 방사성 핵종 직접오염 경로를 분석하기 위하여 동위원소 실험온실내에서 $^{54}Mn,\;^{57}Co,\;^{85}Sr,\;^{134}Cs$의 혼합용액을 벼의 생육중 여섯 차례에 걸쳐 작물체 지상부에 처리하였다. 작물체 차단계수는 핵종 간에 차이가 없었고 처리시기가 수확기에 가까울수록 증가하여 최고 약 0.94에 달리하였다. 작물계에 침적한 각 핵종의 수확시 잔류율은 방사능 붕괴가 없다고 가정할 예 처리시기에 따라 각각 $19{\sim}47%,\;17{\sim}43%,\;19{\sim}42%,\;23{\sim}61%,\;11{\sim}69%$였다. 종실 전류계수는 처리시기에 따라 각각 $6.9{\times}10^{-4}{\sim}3.8{\times}10^{-2},\;3.6{\times}10^{-3},\;1.6{\times}10^{-1}{\sim}5.8{\times}10^{-4}{\sim}3.2{\times}10^{-2},\;1.6{\times}10^{-4}{\sim}7.6{\times}10^{-5},\;3.2{\sim}10^{-2}{\sim}2.0{\times}10^{-1}$의 범위였고 모두 종실의 발육성기 처리시 가장 높았다. 강우 빈도의 차이가 2배 이내일 때는 강우빈도가 잔류율과 전류계수에 큰 영향을 미치지 않는 것으로 나타났다. 본 연구결과는 벼의 생육중 사고침적시 쌀알 내 핵종농도 예측에 활용될 수 있다.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.406-412
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• 2012

This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride ($CCl_4$)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after $CCl_4$ (20 ${\mu}l/kg$) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after $CCl_4$ treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. $CCl_4$ markedly increased serum tumor necrosis factor-${\alpha}$ level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after $CCl_4$ injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin-3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. $CCl_4$ increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased after $CCl_4$ administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-${\kappa}B$ and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates $CCl_4$-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

• Molecules and Cells
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• 제38권7호
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• pp.610-615
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• 2015

Alveolar epithelial cells have been functionally implicated in Mycobacterium tuberculosis infection. This study investigated the role of ursolic acid (UA)-a triterpenoid carboxylic acid with potent antioxidant, anti-tumor, anti-inflammatory, and anti-tuberculosis properties in mycobacterial infection of alveolar epithelial A549 cells. We observed that M. tuberculosis successfully entered A549 cells. Cytotoxicity was mediated by nitric oxide (NO). A549 toxicity peaked along with NO generation 72 h after infection. The NO generated by mycobacterial infection in A549 cells was insufficient to kill mycobacteria, as made evident by the mycobacteria growth indicator tube time to detect (MGIT TTD) and viable cell count assays. Treatment of mycobacteria-infected cells with UA reduced the expression of inducible nitric oxide synthase, NO generation, and eventually improved cell viability. Moreover, UA was found to quench the translocation of the transcription factor, nuclear factor kappa B (NF-${\kappa}B$), from the cytosol to the nucleus in mycobacteria-infected cells. This study is the first to demonstrate the cytotoxic role of NO in the eradication of mycobacteria and the role of UA in reducing this cytotoxicity in A549 cells.

• 한국동물학회지
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• 제33권3호
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• pp.266-275
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• 1990

Onocogene의 일종인 c-raf protein kinase는 세포질 속에 존재하는 serine / threonine-speccific protein이며, 이것은 mitogene signal에 의해 활성화된다. c-raf protein kinase의 구조와 기능은 protein kinase C와 매우 유사한 것으로 생각된다. 면역세포화학적으로 c-raf protein kinase의 signal transduction을 조사하기 위하여 EC-4 세포에 tumor promotor인 12-0-tet-radecanoylphorbol-13-acetae와 mitogenic gactor인 platelet-derived growth factor로 time-course에 따라서 처리하였다. Translocotion되는 c-raf는 먼저 perinuclear membrane에 모이고 그 후에 핵내로 이동되었다. 그런데 TPA와 PDGF로 처리한 c-raf의 translocotion은 각각의 다른 경로를 가짐을 알 수 있었다. TPA와 PAGF을 장기간 처리하였을 때, c-raf protein kinase의 down regulation이 유도됨을 알 수 있었다.

• Molecules and Cells
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• 제28권5호
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• pp.495-499
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• 2009

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

• Reproductive and Developmental Biology
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• 제29권2호
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• pp.101-108
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• 2005

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear $factor-{\kappa}B(NF-{\kappa}B)$ determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce $NF-{\kappa}B$ and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

• 한국식품과학회지
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• 제52권2호
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• pp.138-143
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• 2020

본 연구에서는 다양한 만성 대사성 질환에 기초적 유발 기전인 산화적 스트레스 및 염증에 대한 폴리페놀 함유 블랙 초크베리의 보호 효과를 살펴보았다. 블랙 초크베리는 DPPH, ·OH, 및 NO 등 다양한 라디컬 소거능을 나타냈다. 내독소인 LPS에 의해 활성화된 대식세포 내 ROS 증가는 폴리페놀 함유 블랙 초크베리에 의해 감소하였다. 이는 블랙 초크베리가 전사인자인 NRF2의 핵 내 이동 및 이로 인해 조절되는 SOD에 의한 ROS 소거능 및 NOX2에 의한 ROS 생성 저하에 의한 것으로 나타났다. 블랙 초크베리의 염증 보호 효과는 활성화된 대식세포에서 증가하는 NF-κB의 핵 내 이동에 따른 COX-2, iNOS와 같은 염증 매개인자 관련 효소와 TNF-α, IL-6, IL-1β와 같은 염증성 사이토카인의 저하에 의한 것으로 나타났다. 결론적으로 블랙 초크베리의 산화적 스트레스 및 염증 보호 효과는 항산화 효소 관련 전사 인자인 NRF2 조절 기전 및 염증 관련 전사 인자인 NF-κB와 관련 유전자 발현의 조절을 통하여 나타났다. 추후 블랙 초크베리 내 기능성 물질에 대한 심도 있는 기전 연구를 통해 천연물 유래 기능성 소재로서의 역할을 할 것으로 판단된다.

• Molecules and Cells
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• 제44권1호
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• pp.38-49
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• 2021

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel-forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.