• 생명과학회지
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• 제24권7호
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• pp.769-776
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• 2014

Anisomycin은 Streptomyces griseolus에 의하여 생성되는 항생제의 일종으로 flagecidin으로도 알려져 있으며, ribosomal 28S subunit에 결합함으로서 단백질의 생성을 억제하는 것으로 알려져 있다. TRAIL은 ligand로서의 death receptor와의 결합을 통하여 세포의 apoptosis를 유발하는 것으로 알려져 있으나, 많은 암세포에서는 이미 TRAIL에 대한 저항성을 획득하여 TRAIL 유도 apoptosis를 회피하는 능력을 가지고 있다. 본 연구에서는 TRAIL 저항성 Hep3B 간암세포를 대상으로 anisomycin이 TRAIL 매개 apoptosis를 촉진 시킬 수 있는지의 여부를 조사하였다. 본 연구의 결과에 의하면, 단독 처리 조건에서 Hep3B 세포의 증식에 유의적인 영향을 미치는 않았던 anisomycin과 TRAIL의 동시 처리는 anisomycin 처리 농도 의존적으로 세포의 증식을 시켰으며, 이는 caspase 활성화를 통한 apoptosis 유발 증가와 연관성이 있음을 확인하였다. 특히 siRNA를 이용한 Hep3B 세포의 인위적인 Bid 발현의 차단은 anisomycin과 TRAIL 동시 처리군에 비하여 apoptosis 유발능이 더욱 증대시켜 TRAIL 연관 Bid의 truncation을 통한 미토콘드리아 의존적 apoptosis 유발 과정을 anisomycin이 효과적으로 촉진시켰음을 보여주었다. 따라서 본 연구의 결과는 anisomycin과 TRAIL의 동시 처리는 TRAIL 저항성 암세포의 사멸을 촉진시킬 수 있는 효과적인 방법임을 의미한다.

• BMB Reports
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• 제54권11호
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• pp.545-550
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• 2021

Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

• Bulletin of the Korean Chemical Society
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• 제20권3호
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• pp.321-324
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• 1999

Anisomycin derivatives have been synthesized via syn-amidoalkylation followed by installation of p-methoxy-phenyl group and subsequent transformation.

• Applied Biological Chemistry
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• 제39권2호
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• pp.153-158
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• 1996

광독립 영양세포를 이용하여 미생물유래 제초활성 물질을 탐색하던 중 강한 제초활성을 갖는 균주를 선발하고, 그 균주가 생산하는 활성 물질들을 분리 정제한 후 구조를 결정하였으며, 이들의 활성을 조사하였다. 선발된 ME-13 균주의 미생물학적 특성을 조사한 결과 Streptomyces로 동정되어 본 균주를 Streptomyces sp. ME-13으로 명명하였다. 균배양 상등액으로부터 활성탄소흡착, sillca gel, MCI gel등의 column chromatography 및 HPLC를 통하여 2 가지 활성 물질을 순수 분리하였다. 이들 화합물은 기기분석결과, anisomycin계의 AB3217-A와 B로 각각 동정되었다. AB3217-A와 B는 25ppm 농도에서 무와 피의 종자 발아를 완전히 억제하였고, 종자 발아후 50% 생육저해농도는 약 6 ppm 정도로 서로 비슷하였으며 anisomycin보다 6배 정도 강한 제초활성을 보였다. 이와 같은 제초활성은 본 연구에 의하여 처음으로 밝혀졌다.

• Bulletin of the Korean Chemical Society
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• 제19권1호
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• pp.37-38
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• 1998

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.335-345
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• 2009

A major source of paeoniflorin (PF) which was from the Paeonia lactiflora root, has been used as a herbal medicine in East Asia for its antiallergic, antiinflammatory, and immunoregulatory effects. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by PF using DNA microarrays and computational gene-expression analysis tools in human leukemia U937 cells. A comparative global transcription analysis between treatment with PF and anisomycin (AM) that induces apoptosis in U937 cells revealed that c-Jun-$NH_2$-kinase (JNK) pathway related genes were less expressed in PF-treated cells. Elucidation of the mechanisms by which PF conducts its anti-cancer activities through comparative analysis of the gene expression is necessary to provide a solid foundation for its use as a promising agent in prevention and treatment strategies.

• Journal of Ginseng Research
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• 제43권1호
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.121-129
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• 2018

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.