Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults

Shin, M.J.,Kim, D.W.,Jo, H.S.,Cho, S.B.,Park, J.H.,Lee, C.H.,Yeo, E.J.,Choi, Y.J.,Kim, J.A.,Hwang, J.S.,Sohn, E.J.,Jeong, J.H.,Kim, D.S.,Kwon, H.Y.,Cho, Y.J.,Lee, K.,Han, K.H.,Park, J.,Eum, W.S.,Choi, Pergamon ; Elsevier Science Ltd 2016 FREE RADICAL BIOLOGY AND MEDICINE Vol.97 No.-

Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia. We showed that Tat-PRAS40 transduced into HT-22 cells, and significantly protected against cell death by reducing the levels of H<SUB>2</SUB>O<SUB>2</SUB> and derived reactive species, and DNA fragmentation as well as via the regulation of Bcl-2, Bax, and caspase 3 expression levels in H<SUB>2</SUB>O<SUB>2</SUB> treated cells. Also, we showed that transduced Tat-PARS40 protein markedly increased phosphorylated RRAS40 expression levels and 14-3-3σ complex via the Akt signaling pathway. In an animal ischemia model, Tat-PRAS40 effectively transduced into the hippocampus in animal brain and significantly protected against neuronal cell death in the CA1 region. We showed that Tat-PRAS40 protein effectively transduced into hippocampal neuronal cells and markedly protected against neuronal cell damage. Therefore, we suggest that Tat-PRAS40 protein may be used as a therapeutic protein for ischemia and oxidative stress-induced brain disorders.

국내 HIV 감염자에서의 기회성 감염증에 관한 연구(Ⅱ)

신영오,이주실,이홍래,강춘,남정구,최병선,김상형,민복순,이재상 국립보건연구원 1994 국립보건원보 Vol.31 No.1

Cross-protective efficacies of highly-pathogenic avian influenza H5N1 vaccines against a recent H5N8 virus

Park, S.J.,Si, Y.J.,Kim, J.,Song, M.S.,Kim, S.m.,Kim, E.H.,Kwon, H.i.,Kim, Y.I.,Lee, O.J.,Shin, O.S.,Kim, C.J.,Shin, E.C.,Choi, Y.K. Academic Press 2016 Virology Vol.498 No.-

<P>To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10-40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD(50) of H5N8 virus, with the exception of mice vaccinated with 3.5 mu g of Rg Vietnam/1194/04xPR8. Of note, the Rg Korea/ES223N/03xPR8 vaccine provided not only effective protection, but also markedly inhibited viral replication in the lungs and nasal swabs of vaccine recipients within five days of HPAI H5N8 virus challenge. Further, we demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) of an antibody-coated target cell by cytotoxic effector cells also plays a role in the heterologous protection of H5N1 vaccines against H5N8 challenge. (C) 2016 Elsevier Inc. All rights reserved.</P>

Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway

Park, Y-H,Kim, S-U,Kwon, T-H,Kim, J-M,Song, I-S,Shin, H-J,Lee, B-K,Bang, D-H,Lee, S-J,Lee, D-S,Chang, K-T,Kim, B-Y,Yu, D-Y Macmillan Publishers Limited 2016 Oncogene Vol.35 No.27

<P>The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently- expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.</P>

H. pylori성 위염에서 위축진행과 Myeloperoxidase(MPO) 유전자 다형성(genetic polymorphism)의 관련성

이만용 ( M. Y. Lee ),노임환 ( I. H. Roe ),양미라 ( M. R. Yang ),남승우 ( S. W. Nam ),허재형 ( J. H. Heo ),임창영 ( C. Y. Lim ),송일한 ( I. H. Song ),김정원 ( J. W. Kim ),신지현 ( J. H. Shin ) 대한소화기학회 2002 대한소화기학회 춘계학술대회 Vol.2002 No.-

<목적> H. pylori는 위 점막에서 많은 중성구들의 침윤이 특징적으로 관찰되는 활동성 위염을 일으키며 중성구들에서 나오는 많은 산소라디칼 등은 상피세포의 손상과 apoptosis을 유도하고 위축성 변화로 진전하는데 주도적인 역할을 한다. 특히 중성구의 myeloperioxidase(MPO)는 산소라디칼의 공격적인 산화적 잠재력을 중폭시키고 monochloramine을 생성하여 위세포의 손상과 위축성 변화를 야기한다고 이해되고 있다. 그러나 위축성위

Syntheses, crystal structures, circular dichroism, and magnetic properties of chiral dinuclear and polymeric nickel(II) compounds

Shin, J.W.,Son, H.J.,Kim, S.K.,Min, K.S. Pergamon Press 2013 Polyhedron Vol.52 No.-

Chiral dinuclear nickel(II) complexes, [Ni(L<SUP>R,R</SUP>)(C<SUB>2</SUB>O<SUB>4</SUB>)Ni(L<SUP>R,R</SUP>)](ClO<SUB>4</SUB>)<SUB>2</SUB>.4CH<SUB>3</SUB>CN (3) and [Ni(L<SUP>S,S</SUP>)(C<SUB>2</SUB>O<SUB>4</SUB>)Ni(L<SUP>S,S</SUP>)](ClO<SUB>4</SUB>)<SUB>2</SUB>.4CH<SUB>3</SUB>CN (4) and chiral polymeric compounds, [Ni(L<SUP>R,R</SUP>)(CrO<SUB>4</SUB>)]<SUB>n</SUB>.2H<SUB>2</SUB>O.CH<SUB>3</SUB>CN (5) and [Ni(L<SUP>S,S</SUP>)(CrO<SUB>4</SUB>)]<SUB>n</SUB>.2H<SUB>2</SUB>O.CH<SUB>3</SUB>CN (6) have been synthesized and characterized (L<SUP>R,R/S,S</SUP>=1,8-di((R/S)-α-methylbenzyl)-1,3,6,8,10,13-hexaazacyclotetradecane). These chiral compounds were characterized by X-ray crystallography, circular dichroism, and molecular magnetism. The nickel(II) ions in 3 and 4 have a distorted octahedral geometry by coordination with four nitrogens of a macrocyclic ligand with chiral pendents in a folded conformation and two oxygens of an oxalate ion in the cis positions. The nickel(II) ions in 5 and 6 have a distorted octahedral geometry by coordination with four nitrogens of a macrocyclic ligand in a planar conformation and two oxygens of two chromate ions in the axial positions. Complexes 3 and 4 show strong antiferromagnetic interactions [3: g=2.36, J/k<SUB>B</SUB>=-29.9K (-20.8cm<SUP>-1</SUP>); 4: g=2.18, J/k<SUB>B</SUB>=-25.5K (-17.7cm<SUP>-1</SUP>)], while 5 and 6 exhibit weak antiferromagnetic couplings [5: g=2.25, J/k<SUB>B</SUB>=-1.20K (-0.83cm<SUP>-1</SUP>); 6: g=2.25, J/k<SUB>B</SUB>=-0.68K (-0.47cm<SUP>-1</SUP>)]. The former complexes occur strong antiferromagnetic interactions via the oxalato bridges within the nickel(II) dimers, the latter compounds are weak antiferromagnetic interactions through the chromate ions within the 1D polymers. The circular dichroism (CD) spectrum of 3 has exhibited two negative peaks at 336 and 533nm, and that of 4 has displayed an enantiomeric pattern. The CD spectrum of 5 has appeared a negative absorption above ca. 550nm, while that of 6 has shown an enantiomeric pattern in the same wavelength region.

H. pylori 제균 실패율과 clarithromycin 내성률의 일치성

허재형 ( J. H. Heo ),남승우 ( S. W. Nam ),노임환 ( I. H. Roe ),양미라 ( M. R. Yang ),김정택 ( J. T. Kim ),송일환 ( I. H. Song ),임창영 ( C. Y. Lim ),김정원 ( J. W. Kim ),신지현 ( J. H. Shin ) 대한소화기학회 2002 대한소화기학회 춘계학술대회 Vol.2002 No.-

<목적> H. pylori 제균 치료성적을 좌우하는 요소에는 약제와 대상 환자군의 선정, 균검사방법의 차이, 항생제 저항성 등이 중요시되고 있다. 이 중에서도 항생제 저항성은 나라간의 H. pylori 제균 성적을 다르게 하는 대표적인 원인이다. 우리나라는 제균률이 외국보다 저조하여 85%내외로 보고되고 있다. 본 연구의 목적은 H. pylori 제균 실패율과 clarithromycin 내성률을 조사하여 제균 실패 원인으로서의 clarithromycin

Anti-inflammatory effect of desoxo-narchinol-A isolated from Nardostachys jatamansi against lipopolysaccharide

Shin, J.Y.,Bae, G.S.,Choi, S.B.,Jo, I.J.,Kim, D.G.,Lee, D.S.,An, R.B.,Oh, H.,Kim, Y.C.,Shin, Y.K.,Jeong, H.W.,Song, H.J.,Park, S.J. Elsevier Science 2015 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.29 No.2

We previously reported that Nardostachys jatamansi (NJ) exhibits anti-inflammatory activity against lipopolysaccharide (LPS). However, the active compound in NJ is unknown. Therefore, here, we examined the effects of desoxo-narchinol-A (DN) isolated from NJ against LPS-induced inflammation. To demonstrate the anti-inflammatory effect of DN against LPS, we used two models; murine endotoxin shock model for in vivo model, and peritoneal macrophage responses for in vitro. In endotoxin shock model, DN was administrated intraperitoneally 1h before LPS challenge, then we evaluated mice survival rates and organ damages. Pretreatment with DN (0.05mg/kg, 0.1mg/kg, or 0.5mg/kg) dramatically reduced mortality in a murine LPS-induced endotoxin shock model. Furthermore, DN inhibited tissue injury and production of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), in the liver and lung. In in vitro macrophage model, we examined the inflammatory mediators and regulatory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB). DN inhibited the production of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and its derivative nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), IL-1β, IL-6 and TNF-α and H3 protein acetylation in murine peritoneal macrophages. DN also inhibited p38 activation, but not extracellular signal-regulated kinase (ERK), c-jun NH<SUB>2</SUB>-terminal kinase (JNK), and NF-κB. These results suggest that DN from NJ exhibits protective effects against LPS-induced endotoxin shock and inflammation through p38 deactivation.

Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication

Shin, C. M.,Kim, N.,Chang, H.,Kim, J. S.,Lee, D. H.,Jung, H. C. Plenum Pub. Corp 2016 Digestive diseases and sciences Vol.61 No.4

<P>Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet. To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM). Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H. pylori eradication therapy. Forty-four subjects were H. pylori negatives. Expression levels in CDX1 and CDX2 from noncancerous gastric mucosae of the corpus, as well as the histologic findings of gastric mucosae, were evaluated during the follow-up. Average follow-up duration was 33.7 months (range 2-97 months). Expression levels in both CDX1 and CDX2 mRNAs were correlated with IM grade in the corpus (rho = 0.633 and 0.554, respectively, all P < 0.001). Changes in CDX1/CDX2 mRNA expressions following H. pylori eradication showed only insignificant results; IM grade at the antrum and corpus showed a tendency to decrease after H. pylori eradication without statistical significance (P > 0.05). However, histologic improvement of IM at the corpus was associated with a decrease in CDX2 mRNA expression during the follow-up (linear mixed model, P for slope = 0.015). In this study, eradication of H. pylori did not show any beneficial effects on aberrant CDX1/CDX2 expressions or IM. Reversibility of IM may be associated with a decrease in CDX2 mRNA expression.</P>

Display of membrane proteins on the heterologous caveolae carved by caveolin-1 in the Escherichia coli cytoplasm

Shin, J.,Jung, Y.H.,Cho, D.H.,Park, M.,Lee, K.E.,Yang, Y.,Jeong, C.,Sung, B.H.,Sohn, J.H.,Park, J.B.,Kweon, D.H. IPC Science and Technology Press ; Elsevier Scienc 2015 Enzyme and microbial technology Vol.79 No.-

Caveolae are membrane-budding structures that exist in many vertebrate cells. One of the important functions of caveolae is to form membrane curvature and endocytic vesicles. Recently, it was shown that caveolae-like structures were formed in Escherichia coli through the expression of caveolin-1. This interesting structure seems to be versatile for a variety of biotechnological applications. Targeting of heterologous proteins in the caveolae-like structure should be the first question to be addressed for this purpose. Here we show that membrane proteins co-expressed with caveolin-1 are embedded into the heterologous caveolae (h-caveolae), the cavaolae-like structures formed inside the cell. Two transmembrane SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, Syntaxin 1a and vesicle-associated membrane protein 2 (VAMP2), were displayed on the h-caveolae surface. The size of the h-caveolae harboring the transmembrane proteins was ~100nm in diameter. The proteins were functional and faced outward on the h-caveolae. Multi-spanning transmembrane proteins FtsH and FeoB could be included in the h-caveolae, too. Furthermore, the recombinant E. coli cells were shown to endocytose substrate supplemented in the medium. These results provide a basis for exploiting the h-caveolae formed inside E. coli cells for future biotechnological applications.