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Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells
Kim, Sang Bum,Kim, Hye Rim,Park, Min Chul,Cho, Seongmin,Goughnour, Peter C.,Han, Daeyoung,Yoon, Ina,Kim, YounHa,Kang, Taehee,Song, Eunjoo,Kim, Pilhan,Choi, Hyosun,Mun, Ji Young,Song, Chihong,Lee, Sang Rockefeller University Press 2017 The Journal of cell biology Vol.216 No.7
<P>Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.</P>
( Hyosun Cho ),( Chang Wook Kim ),( Ji Young Kim ),( Yun Hui Kim ),( Seok Cheon Yeom ),( Su Gyeong Lee ),( Hee Yeon Kim ),( Si Hyun Bae ),( Jong Young Choi ),( Seung Kew Yoon ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Immune regulatory molecules such as forkhead box P3 (Foxp3) on CD4+ T cell and programmed death-1 (PD-1) and cytotoxic T lymphocyte- associated antigen 4 (CTLA-4) on CD8+ T cell are associated with antiviral effector T cell dysfunction, which influences on T cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B, These Foxp3, PD-1 and CTLA-4 are up-regulated in chronic viral infection such as chronic hepatitis C, chronic hepatitis B and human immunodeficiency virus infection but there is few report about the role of Foxp3, PD-1 and CTLA-4 in patients with chronic hepatitis B during antiviral therapy with tenofovir. We investigated the expression of Foxp3, PD-1 and CTLA-4 during 1 year tenofovir treatment in patients with chronic hepatitis B. Methods: Thirty patients with chronic hepatitis B under tenofovir treatment were enrolled for detection of Foxp3, PD-1 and CTLA-4 on T cells. Peripheral blood mononuclear cells (PBMC) were isolated from these subjects before tenofovir treatment (T0), 1 month (T1), 3 month T3), 6 month (T6) and 12 month (T12) during tenofovir treatment. The expressions of Foxp3, PD-1 and CTLA-4 on T cells were monitored by flow cytometry. Results: T cells from patients with chronic hepatitis B under tenofovir treatment showed decreased expression of Foxp3 and PD-1 at T12 compared to T0 significantly but, the expression of CTLA-4 were decreased initially then increased at T12 compared to T0. Conclusions: In chronic hepatitis B, PD-1 as inhibitory T cell molecules and FoxP3 as regulatory T cell marker are down-regulated during 1 year tenofovir therapy, which could restore HBV-specific T cell function during tenofovir antiviral therapy. Interestingly, CTLA-4 may be up-regulated during 12 months tenofovir therapy in chronic hepatitis B, may play an important role in failing to eradicate HBV in spite of complete virologic response with tenofovir.
( Seokhwan Kim ),( Hansol Kim ),( Hai-seong Kang ),( Yonghoon Kim ),( Migyeong Kim ),( Hyosun Kwak ),( Sangryeol Ryu ) 한국미생물생명공학회(구 한국산업미생물학회) 2020 Journal of microbiology and biotechnology Vol.30 No.12
The spread of plasmid-mediated colistin resistance has posed a serious threat to public health owing to its effects on the emergence of pandrug-resistant bacteria. In this study, we investigated the prevalence and characteristics of mcr-1-positive Escherichia coli isolated from retail meat samples in Korea. In total, 1,205 E. coli strains were isolated from 3,234 retail meat samples in Korea. All E. coli strains were subjected to antimicrobial susceptibility testing and were examined for the presence of mcr-1 gene. All mcr-1-positive E. coli (n = 10, 0.8%) from retail meat were subjected to pulse-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). The transferability of mcr-1 gene was determined by conjugation assays. The mcr-1-positive strains exhibited diverse clonal types. Our mcr-1 genes were located in plasmids belonged to the IncI2 (n = 1) and IncX4 (n = 8) types, which were reported to be prevalent in Asia and worldwide, respectively. Most mcr-1 genes from mcr-1-positive strains (9/10) were transferable to the recipient strain and the transfer frequencies ranged from 2.4 × 10<sup>-3</sup> to 9.8 × 10<sup>-6</sup>. Our data suggest that the specific types of plasmid may play an important role in spreading plasmid-mediated colistin resistance in Korea. Furthermore, our findings suggest that the retail meat may be an important tool for disseminating plasmid-mediated colistin resistance.
김동하(Dongha Kim),김민정(Minjeong Kim),김희수(Heesu Kim),양동준(Dongjoon Yang),임승록(Seungrok Lim),김효선(Hyosun Kim) 한국HCI학회 2013 한국HCI학회 학술대회 Vol.2013 No.1
태블릿 PC에서 활용되는 "필기노트" 어플리케이션의 사용성을 향상시키고자 인터뷰와 설문을 실시하였다. 인터뷰와 설문을 통해서 필기노트 어플리케이션의 필기모드에서 사람들이 선호하는 기능 제공 방식과 그 이유들을 분석 하였다. 본 연구의 결과는 필기노트 어플리케이션 제작 시 고려해야할 사항을 발견할 수 있다는 것에 의의가 있으며, 향후 해당 어플리케이션의 사용성 발전에 도움이 될 것이다. In this paper, the result of survey and interview provides suggestions to improve usability for "Writing application" using tablet PC. Through this interview and survey, we found out the preferable method of providing different functions when using writing application. Through this analysis, what to be considered before designing writing application is presented in details and it can be considered when improving usability.
Kim, Kibong,Choi, Shin Hei,Jeon, June,Lee, Hyosun,Huh, Jung Oh,Yoo, Jaeduk,Kim, Jong Taek,Lee, Chang-Hee,Lee, Yoon Sup,Churchill, David G. American Chemical Society 2011 Inorganic Chemistry Vol.50 No.12
<P>One 8-phenyl and two 8-mesityl-substituted “scorpionate”-like BODIPY-type species of the formula [3,4,4-tris(5-<I>R</I>-(2-thienyl))-8-(2,4,6-<I>R′</I>-phenyl)-4-bora-3a,4a-diaza-<I>s</I>-indacene (R = H, R′ = H, <B>3a</B>; R, = H, R′ = Me, <B>2a</B>; R, = Me, R′ = Me, <B>2b</B>)] have been synthesized and fully characterized. Importantly, differences in their solution (MeCN) optical Cu<SUP>2+</SUP> and Hg<SUP>2+</SUP> probing capacity via <I>SSS</I>-chelation were investigated. Compounds <B>2a</B>–<B>3a</B> were prepared from the requisite 8-substituted BODIPY complexes. They were characterized first by complete <SUP>1</SUP>H, <SUP>11</SUP>B and <SUP>13</SUP>C NMR spectroscopic assignments (CD<SUB>3</SUB>Cl or CD<SUB>3</SUB>C(O)CD<SUB>3</SUB>); the molecular structures of <B>2a</B> and <B>3a</B> were determined by X-ray crystallography. Compounds <B>2a</B>–<B>3a</B> were studied by UV–vis and fluorescence spectroscopy [Φ<SUB>F</SUB> = 0.27 ± 0.013 (<B>2a</B>); 0.024 ± 0.0016 (<B>2b</B>); 0.0034 ± 0.00047 (<B>3a</B>)]. Importantly, low [Cu<SUP>2+</SUP>] with <B>3a</B> (<3.0 × 10<SUP>–5</SUP> M) gave rise to an increase of fluorescence intensity (off–on; 6.3-fold), whereas with <B>2a</B> it decreased (on–off). When [Hg<SUP>2+</SUP>] (<3.0 × 10<SUP>–5</SUP> M) was added to <B>2b</B>, the λ<SUB>em,max</SUB> value increased (off–on<I>;</I> 3.2-fold), and for <B>2a</B>, it decreased (on–off). The association constant (<I>K</I><SUB>a</SUB>) for Hg<SUP>2+</SUP>·<B>2a</B> was determined to be 3120 ± 307 M<SUP>–1</SUP>. An approximate stoichiometric 1:1 binding determined by Job plot analysis is in line with successful DFT modeling of <I>SSS</I>-Cu<SUP>2+</SUP> binding for this system type. <SUP>1</SUP>H NMR spectroscopy also revealed tentative sets of product complex peaks. These simple differences caused by formal ligand Me-group incorporation are the first for any related fluorophores, to the best of our knowledge.</P><P>Three new “scorpionate”-like BODIPY species have been isolated and characterized. They exposed interesting differences in low [Cu<SUP>2+</SUP>] and [Hg<SUP>2+</SUP>] on−off and off−on fluorescence responses through formal methyl group placement into the fluorophore skeleton.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/inocaj/2010/inocaj.2010.50.issue-12/ic101681h/production/images/medium/ic-2010-01681h_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ic101681h'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ic101681h'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ic101681h'>ACS Electronic Supporting Info</A></P>