• Biomolecules & Therapeutics
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• 제20권4호
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• pp.393-398
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• 2012

Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

• The Plant Pathology Journal
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• 제15권6호
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• pp.323-329
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• 1999

Anthracnose of pepper casued by Colletotrichum spphas been a great problems for pepper production in Korea and China. Especially Colletotrichum gloeosporioides was found predominantly over cultivation areas during infection periods and caused severe rots on bath unripe and ripe fruits that resulted in major yield losses. In this study, comparison of Colletrichum spp.isolated from Korea and China in morphology and pathgenicity, and RAPD-PCR analysis were conducted. Based on morphological characteristics, the pathogen isolates, K1 and C1, K2 and C2, and K3 and C3 were identified as Colletotrichum gloeosporioides (G) type, C. gloeosporioides (R) type and C. coccodes, respectively. in pathogenicity test, K1 and C1, and K2 and C2 were found to attack mainly fruits and to be the most virulent among isolates. K3 and C3 were strongly virulent to leaves and seedling. Pathogenicity between Korean and Chinese isolates. K3 and C3 were strongly virulent to leaves and seedling. Pathogenicity between Korean and Chinese isolates did not show any difference. Results of the RAPD-PCR analyses indicate the varying levels of molecular diversity within and between Colletotrichum spp.of Korea and China. The similarities between K1 and C1, K2 and C2, and K3 and C3 were 85.71%, 71.43% and 50.0% respectively.

• 대한기계학회논문집A
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• 제31권11호
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• pp.1108-1114
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• 2007

The low kinds of $Al_2O_3$ composite ceramics were prepared using a mixture of 85 wt.% $Al_2O_3$ (mean size $0.5\;{\mu}m$), 15 wt.% SiC Powder with $Y_2O_3$, as an additive powder (0, 1, 3 and 5 wt.%). The crack-healing strengths were studied as functions of crack-healing temperature and amount of $Y_2O_3$. The in-situ crack-healing behavior was observed at 1,573 K for 1 h in the air. The heat treated specimen with 3 wt.% of $Y_2O_3$ showed better crack-healing ability than specimen with 1 or 5 wt.% of $Y_2O_3$. In case of specimen with 3 wt.% of $Y_2O_3$, the bending strength of the crack-healed specimen at 1,473 K was recovered to the bending strength of smooth specimen treated at 1573 K. The heat-resistance limit temperature of $Al_2O_3$ composite ceramics was 1,073 K, 1,373 K, 873 K for the specimen with 1, 3, 5 wt.% of $Y_2O_3$.

• 한국자기학회지
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• 제17권3호
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• pp.114-119
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• 2007

[ $bcc-Th_3P_4$ ] 구조를 가지고 있는 단결정 $Nd_3Se_4$를 성장 시킨 후 $4{\sim}300\;K$ 사이의 온도 영역에서 자기감수율을 측정했다. 측정된 자기기감수율을 축퇴된 $Nd^{3+}$ 기저상태가 결정장의 영향을 받아 발생하는 에너지 갈라짐에 의한 이론적인 자기감수율값과 비교했다. 분석 결과 $Nd_3Se_4$ 결정체 안에 있는 $Nd^{3+}$ 이온의 경우에는 결정장에 의한 영향이 거의 없음을 알 수 있었다. 또한 $T_c$가 53 K인 $Nd_3Se_4$의 자발자기화의 온도에 따른 곡선이 J=9/2에 해당하는 Brillouin function과 일치함을 확인했다.

• 미생물학회지
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• 제52권4호
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• pp.487-494
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• 2016

출아 효모에서의 Paf1 복합체는 총5개의 단백질로 구성되어있고, 구성성분들은 출아효모, 초파리, 식물들, 그리고 인간에 이르기까지 구조적으로, 기능적으로 잘 보존되어 있다. RNA 중합효소 II와 결합한 상태로 전사 개시부위부터 종결부위까지 함께 이동하며, 여러 전사인자들의 유입을 위한 매개체로 작용하여, 유전자 발현 조절의 핵심적인 역할을 수행한다. Paf1 복합체는 H2BK123 monoubiquitination에 기여하고, histone crosstalk에 의해 간접적으로 H3K4의 di-, tri-methylation에 기여하는 것이 알려져 있다. 하지지만, Paf1 복합체 구성요소들의 개별적인 기능에 대해서는 연구가 되어있지 않다. 이 연구에서는, Paf1 복합체 구성요소들의 단일 결핍 돌연변이 균주를 만든 후, 이들의 H2BK123 monoubiquitination 및 H3K4 mono-, di-, tri-methylation에 미치는 영향을 관찰했다. 놀랍게도, ${\Delta}paf1$, ${\Delta}rtf1$, ${\Delta}ctr9$ 돌연변이 균주에서는 H2Bub에 영향을 받는 H3K4me2와 H3K4me3뿐 아니라, H2B monoubiquitination에 영향을 받지 않는 H3K4 monomethylation의 심각한 감소를 관찰했다. 그러나, methyl기 전달 효소인 Set1의 발현 정도는 이 돌연변이 균주들에서 변하지 않았다. 이러한 결과로부터, Paf1 복합체가 Set1의 활성이나 Set1 복합체의 안정성을 직접 조절함으로써 H3K4 methylation을 조절할 수 있음을 제시한다.

• 한국임상약학회지
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• 제13권1호
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• pp.29-39
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• 2003

Neurodegenerative disorders are associated with apoptosis as a causing factor or an inducer. On the other hand, it has been reported that epigallocatechin gallate (EUG), one of antioxidants and flavonoids, and z-VAD-fmk, a nonselective caspase inhibitor, suppress oxidative-radical-stress-induced apoptosis. However, it is not yet known what is the effects of EGCG and z-VAD-fmk on the apoptotic pathway is through phosphoinositide 3-kinase (PI3K), Akt and glycogen synthase kinase-3 (GSK-3) as well as mitochondria, caspase-3 and poly (ADP-ribose) polymerase (PARP). We investigated the effects of EGCG by using $H_2O_2$ treated N18D3 cells, mouse DRG hybrid neurons. Methods: Following 30 min $100\;{\mu}m\;H_2O_2$ exposure, the viability of N18D3 cells (not pretreated vs. EGCG or z-VAD-fmk pretreated) was evaluated by using MTT assay. The effect of EGCG on immunoreactivity (IR) of cytochrome c, caspase-3, PARP, PI3K/Akt and GSK-3 was examined by using Western blot, and was compared with that of z-Y4D-fmk. Results: EGCG or z-VAD-fmk pretreated N18D3 cells showed increased viability. Dose-dependent inhibition of caspase-3 activation accompanied by PARP cleavage were demonstrated by pretreatment of both agents. However, inhibition of cytochrome c release was only detected in EGCG pretreated N18D3 cells. On the pathway through PI3K/Akt and GSK-3, however, the result of Western blot in EGCG pretreated N18D3 cells showed decreased IR of Akt and GSK-3 and increased IR of p85a PI3K, phosphorylated Akt and GSK-3, and contrasted with that in z-VAD-fmk pretreated N18D3 cells showing no changes on each molecule. Conclusion: These data show that EGCG affects apoptotic pathway through upstream signal including PI3K/Akt and GSK-3 pathway as well as downstream signal including cytochrome c and caspase-3 pathway. Therefore, these results suggest that EGCG mediated activation of PI3K/Akt and inhibition GSK-B could be new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.

• 약학회지
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• 제40권1호
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• pp.46-51
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• 1996

Eight new D-1.3-dioxolanyl and L-1,3-oxathiolanyl nucleosides containing 5-phenyl- selenyl pyrimidine bases which are expected to have antiviral activity were synthesized. Condensation of D-1,3-dioxolane acetate and L-1,3-oxathiolane acetate with 5-phenylselenyl pyrimidines gave anomeric mixtures of their nucleosides which were separated by silicagel column chromatography.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.172-183
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• 2020

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

• 대한화학회지
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• 제47권6호
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• pp.585-590
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• 2003

코발트 산소 운반체인 N,N''-ethylenebis(3-methoxysalycylideneiminato)cobalt(II), Co(3MeOsalen)을 $25{\circ}C$에서 합성하였다. 이 착물과 하이드라조벤젠의 자외선 및 가시부분 광스펙트럼은 파장 범위 200-600 nm에서 비수용매 메탄올을 사용하여 연구하였다. 하이드라조벤젠의 산소와의 산화반응은 메탄올에서 Co(3MeOsalen) 촉매로 사용하였다. 트라이페닐포스핀($PPh_3$) 존재하에서, 반응속도는 감소하였으며 이는 촉매가 리간드 트라이페닐포스핀과 배위화합된 것으로 추정되며 촉매가 비활성인 Co(3MeOsalen)$(PPh_3)_2$으로 되어 속도가 급격히 떨어지는 것으로 생각된다. 리간드 트라이페닐포스핀과 하이드라조벤젠의 초기산화속도는 이론속도식, Rate=$k_1+k_2K_1[P]/1+K_1[P]+K_1K_2[P]^2$으로 측정되었다. 이것은 리간드가 메탄올 분자보다 더 좋지않은 σ-주게일 것으로 간주된다.

• 생명과학회지
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• 제17권3호통권83호
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• pp.386-395
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• 2007

본 연구는 1999년에서 2001년도 걸쳐서 3년간 국내에서 분리된 환자유래 장염비브리오 18균주와 일본 후쿠오카 지역에서 2002년도에 환자에서 분리한 장염비브리오 9균주 등 총 27균주에 대하여 toxR 유전자의 검출, 혈청형별 검사, 약제내성의 양상, tdh, trh1 및 trh2 유전자의 보유상태 및 urease 생성성을 살펴보고, 혈청형 O3:K6 균주에 대하여 TDH의 생성성 검사, tdh 양성균주의 RFLP 형별, ORF 8의 분포, PFGE법과 RAPD법을 실시하였으며 결과는 다음과 같다. 1. 한국 및 일본의 환자유래 균주 대부분에서 urease음성이었으며, toxR 유전자로 확인 동정하였고 혈청형의 분포는 국내 분리 주의 O3:K6, O4:K9, O6:K46, O3:K57, O5:Kl5와 일본 분리주의 O3:K6, O1:K38, O4:K68, O4:Kl2의 혈청형으로 나타났다. 2. 항생제 감수성 시험에서는 vancomycin과 oxacillin은 27균주 (100%), penicillin은 26균주 (96.3%)로 높은 내성을 나타내었고, 14균주 (51.9%)가 4가지 이상의 항생제에 다제내성을 나타내었다. 항생제의 내성양상은 6종류로 혈청형에 관계없이 vancomycin, oxacillin, penicillin에 내성을 나타내는 V형이 15균주 (55.6%)로 가장 많이 나타났다. 3. tdh 유전자는 26균주가 PCR법과 DNA probe hybridization법의 결과에서 양성으로 나타났으며, urease양성이었던 일본 환자유래 혈청형 O3:K6 1균주만이 tdh유전자 음성, trh2 유전자 양성을 나타냈다. 혈청형 O3:K6의 TDH 생성성역가는 전 균주가 256배에서 2,048배 정도로 나타났으며, RFLP 양상은 모든 균주가 11.5 kb와 4.3 kb에 tdh 유전자를 보유하고 있었다. 또한 혈청형 O3:K6 균주들은 RAPD법과 PFGE법으로 유전자형별을 비교 검토한 결과 8형으로 거의동일한 유전자형별의 결과를 나타내었다. 4. ORF 8의 분포는 혈청형 O3:K6 전 균주에서 양성이었고, 특히 혈청형 O6:K46 4균주 모두에서 ORF 8 양성을 나타내어 새롭게 나타난 유행균주일 가능성을 시사 하였다. 따라서 ORF 8 유전자의 검출은 범세계적으로 유행하는 균주들을 동정하는데 있어 genetic marker로서 매우 유용한 것으로 사료된다.