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Kim, Ji Yeon,Hwang, Joo-Yeon,Lee, Dae Yeon,Song, Eun Hyun,Park, Keon Jae,Kim, Gyu Hee,Jeong, Eun Ae,Lee, Yoo Jeong,Go, Min Jin,Kim, Dae Jin,Lee, Seong Su,Kim, Bong-Jo,Song, Jihyun,Roh, Gu Seob,Gao, Bi American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.39
<▼1><P><B>Background:</B> Chronic ethanol consumption induces pancreatic β-cell dysfunction and metabolic syndrome.</P><P><B>Results:</B> Ethanol-induced Atf3 inhibits glucokinase transcriptional activity through direct binding or Atf3/Pdx-1/Hdac1 axis on glucokinase promoter.</P><P><B>Conclusion:</B> ATf3 fosters β-cell dysfunction via <I>Gck</I> down-regulation and triggers T2D, which is ameliorated by <I>in vivo Atf3</I> silencing.</P><P><B>Significance:</B> The presented data uncover a new role for Atf3 as a potential therapeutic target in treating type 2 diabetes.</P></▼1><▼2><P>Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that <I>Gck</I> gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure <I>in vivo</I> and <I>in vitro</I>, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the <I>Gck</I> promoter were up-regulated. Furthermore, <I>in vitro</I> ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on <I>Gck</I> transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the <I>Gck</I> promoter, which were diminished by <I>Atf3</I> siRNA. <I>In vivo Atf3</I>-silencing reversed ethanol-mediated <I>Gck</I> down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced <I>Atf3</I> fosters β-cell dysfunction via <I>Gck</I> down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The <I>Atf3</I> gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis.</P></▼2>
Kim, Hyun‐,Ouk,Kim, Eunjung,An, Yonghee,Choi, Jihye,Jang, Eunji,Choi, Eun Bi,Kukreja, Aastha,Kim, Myeong‐,Hoon,Kang, Byunghoon,Kim, Dong‐,Joo,Suh, Jin‐,Suck,Huh, Yong‐,Mi WILEY‐VCH Verlag 2013 Macromolecular bioscience Vol.13 No.6
<P><B>Abstract</B></P><P>Combined cancer treatment via co‐delivery of siRNAs and an anticancer drug can be a promising strategy due to the synergistic effect of simultaneously minimizing gene/drug administration. In this study, Bcl‐xL siRNA and doxorubicin (DOX) are encapsulated into designed methoxy‐poly(ethylene glycol)‐<I>block</I>‐poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>‐lactic acid) (mPEG‐<I>b</I>‐PLA) block copolymer polymersomes (PSomes). A study of the cytotoxicity of Bcl‐xL siRNA and DOX co‐encapsulated PSomes (CPSomes) shows more inhibited proliferation of MKN‐45 and MKN‐28 human gastric cancer cell lines than only gene‐ and drug‐loaded ones. Consequently, these results demonstrate that co‐delivery of genes and drugs using PSomes results in a synergistic efficacy and indicates the potential of PSomes as efficient nanocarriers for combined cancer therapy. </P>
Ferromagnetism in single crystal and nanocomposite Sr(Ti,Fe)O<sub>3</sub> epitaxial films
Kim, Hyun-Suk,Bi, Lei,Kim, Dong Hun,Yang, Dae-Jin,Choi, Yoon Jeong,Lee, Jung Woo,Kang, Jeung Ku,Chang Park, Yun,Dionne, Gerald F.,Ross, Caroline A. Royal Society of Chemistry 2011 Journal of materials chemistry Vol.21 No.28
<P>The ferromagnetic properties and electrical leakage current of single-phase SrTi<SUB>1−<I>x</I></SUB>Fe<SUB><I>x</I></SUB>O<SUB>3</SUB> (STF) perovskite films are compared for two different samples: a single-crystal film with a (100) orientation, and a ‘doubly oriented’ nanocomposite film consisting of (110)-oriented nanopillars embedded homoepitaxially in a (100)-oriented matrix. The STF films contain mixed valence Fe ions, with a lower average valence state present in the single crystal film. The films are under an in-plane compressive strain, and exhibit an out-of-plane magnetic easy axis due to magnetoelastic effects. The nanopillars in the double-epitaxial STF films act as single ferromagnetic domains, whereas the single-crystal films show a maze-like domain structure. Composition fluctuations seen in single-crystal films are suppressed in the double-epitaxial structure, which has a lower electrical leakage current. First-principles modeling supports a tendency for Fe ions to occupy adjacent sites. The correlations between the valence state and distribution of the Fe ions, the microstructure, and the magnetic and electrical properties provide a general method of tailoring the properties of perovskite films, which have immense technological value in a range of multiferroic, ferromagnetic, optical, spintronic and hybrid devices.</P> <P>Graphic Abstract</P><P>The ferromagnetic and electrical properties of SrTi<SUB>1−<I>x</I></SUB>Fe<SUB><I>x</I></SUB>O<SUB>3</SUB> films grown on buffered Si are characterized for both (100)-oriented single crystal films and double-epitaxial films consisting of (110)-oriented nanopillars embedded homoepitaxially in a (100)-oriented matrix. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1jm11286d'> </P>
Hyun-Bi Kim,전종성,Jung-Il Cho,Nayeon Ryoo,Shaohong Qu,Guo-Liang Wang 한국분자세포생물학회 2012 Molecules and cells Vol.33 No.1
The development of rapid and efficient strategies to gen-erate selectable marker-free transgenic plants could help increase the consumer acceptance of genetically modified (GM) plants. To produce marker-free transgenic plants without conditional treatment or the genetic crossing of offspring, we have developed a rapid and convenient DNA excision method mediated by the Cre/loxP recombination system under the control of a -46 minimal CaMV 35S promoter. The results of a transient expression assay showed that -46 minimal promoter::Cre recombinase (-46::Cre) can cause the loxP-specific excision of a selectable marker, thereby connecting the 35S promoter and -glucuronidase (GUS) reporter gene. Analysis of stable transgenic Arabidopsis plants indicated a positive correlation between loxP-specific DNA excision and GUS expression. PCR and DNA gel-blot analysis further revealed that nine of the 10 tested T1 transgenic lines carried both excised and non-excised constructs in their genomes. In the subsequent T2 generation plants, over 30% of the individuals for each line were marker-free plants harboring the excised construct only. These results demonstrate that the -46::Cre fusion construct can be efficiently and easily utilized for producing marker-free transgenic plants.
인간 HepG2 Cell에서 항산화 효소의 mRNA 발현에 대한 잔대 에틸아세테이트 추출물 효과
최현진(Hyun-Jin Choi),김수현(Soo-Hyun Kim),오현택(Hyun-Taek Oh),정미자(Mi-Ja Chung),최승필(Cheng-Bi Cui),함승시(Seung-Shi Ham) 한국식품영양과학회 2008 한국식품영양과학회지 Vol.37 No.10
잔대 뿌리는 우리나라에서 예로부터 민간약으로 이용되어 오고 있다. 본 연구에서는 인간 간세포인 HepG2에 잔대 뿌리의 에틸아세테이트 추출물을 처리했을 때 sodium nitroprusside(SNP)에 의해 유도된 세포 독성 및 항산화 유전자 발현에 미치는 영향력을 알아보았다. 먼저, 잔대 에틸아세테이트 추출물이 NO에 의해 유도된 세포 사멸을 저해할 수 있는지를 알아보기 위하여 HepG2 세포에 잔대 에틸아세 테이트 추출물(각각 50과 100 ㎍/mL)을 24시간 먼저 처리한 후 세포내에서 NO을 생성시킬 수 있는 0.5 mM SNP를 처리하였다. NO에 의한 세포독성이 에틸아세테이트 추출물에 의해 저해되었다는 것을 mitochondrial dehydrogenase 활성을 알아보는 MTT assay를 실시하여 알아보았다. 더하여 우리는 잔대 에틸아세테이트 추출물이 세포내 항산화 방어 시스템인 Cu,Zn superoxide dismutase(SOD 1), Mn SOD(SOD 2), glutathione peroxidase(GPx), catalase와 glutathione metabolism과 관련되어져 있는 glutathione reductase(GR), γ-glutamyl-cystein synthetase(GCS), glutathione-S-transferase(GST), γ-glutamyltranspeptidase (γ-GT), glucose-6-phosphate dehydrogenase(G6PD)의 mRNA 발현에 미치는 영향을 RT-PCR로 알아보았다. CAT, GCS 그리고 G6PD mRNA 수준이 잔대 에틸아세테이트 추출물 처리 후 증가하였으나, SOD 1, SOD 2, GPx, GST 그리고 γ-GT mRNA 수준은 변화지 않았다. 따라서 잔대 에틸아세테이트 추출물이 간접적 항산화 효과가 있고, 이들 효과는 아마 CAT, GCS, GR 그리고 G6PD 유전자 발현 증가에 의한 것이라고 추정되었다. The root of Adenophora triphylla is widely used as traditional herbal medicine in Korea. We studied its effects on sodium nitroprusside (SNP) cytotoxicity and antioxidant genes expression in HepG2 cells. To study whether Adenophora triphylla ethylacetate extract (ATea) inhibited NO-induced cell death, HepG2 cells were preincubated for 24 hr with 50 and 100 ㎍/mL ATea followed by 24-hr exposure to 0.5 mM SNP (exogenous NO donor). No-induced cytotoxicity was inhibited by pretreatment of ATea, as assessed by mitochondrial dehydrogenase activity (MTT assay). We further investigated the effects of ATea on mRNA levels of various enzymes of the antioxidant system such as Cu, Zn superoxide dismutase (SOD 1), Mn SOD (SOD 2), glutathione peroxidase (GPx), catalase and several enzymes of the glutathione metabolism [glutathione reductase (GR), γ-glutamyl-cystein synthetase (GCS), glutathione-S-transferase (GST), γ-glutamyltranspeptidase (γ-GT), glucose-6-phosphate dehydrogenase (G6PD)] by RT-PCR. CAT, GCS, GR and G6PD mRNA levels were increased after treatment with ATea. The SOD 1, SOD 2, GPx, GST and γ-GT mRNA levels were not affected in ATea-treated HepG2 cells. We concluded that ATea have an indirect antioxidant effects, perhaps via induction of CAT, GCS, GR and G6PD.
( Ji Hyun An ),( Young Suk Lim ),( Ki Ae Kim ),( Dan Bi Lee ),( Ju Hyun Shim ),( Kang Mo Kim ),( Han Chu Lee ),( Young Hwa Jung ),( Yung Sang Lee ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: It has been suggested that the existence of large spontaneous porto-systemic shunt is frequent cause of recurrent hepatic encephalopathy (HEP). Occlusion of the shunt may prevent the recurrence of HEP. However, little is known about its effect and suitable candidates. Methods: Data of 20 patients who underwent occlusion of porto-systemic shunt for recurrent HEP between 2006 and 2011 in a single tertiary referral hospital were analyzed. Results: Median age of patients was 63 years (range, 48-79 years), and 11 (55%) were males. The number of patients with Child-Turcott-Pugh (CTP) class B and C was 12 and 8, respectively. Shunt occlusion failed technically in 3 patients, and all of them had CTP class C. There was significant difference in overall survival after shunt occlusion between patients with CTP B and C (1-year survival 89% vs. 20%, p < 0.01). The median survival time for patients with CTP C was 4 months. The number of HEP episodes and hospitalization due to HEP during 3 months before and after shunt occlusion significantly decreased in patients with CTP B (4.83 vs. 0.08, p<0.01 and 1.67 vs. 0.08, p < 0.01, respectively). Among patients with CTP class B, CTP and MELD score improved in 9 (75.0%) and 6 (50.0%) patients, respectively, within 3 months after shunt occlusion. Hepatic decompensation and hepatorenal syndrome after occlusion occurred only in 3 patients with Child C. Conclusions: Occlusion of spontaneous porto-systemic shunt is effective in preventing HEP particularly in patients with CTP class B. In some patients with CTP class B, improvement of liver function can also be expected. However, it should be carefully considered in patients with CTP class C.