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BCI induces apoptosis via generation of reactive oxygen species and activation of intrinsic mitochondrial pathway in H1299 lung cancer cells

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Science China(Life Sciences) 2018年第10期61卷 1243-1253页

作者： Jong-Woon Shin Sae-Bom Kwon Yesol Bak Sang-Ku Lee Do-Young Yoon Department of bioscience and biotechnology Konkuk University Targeted Medicine research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)

The compound(E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1 H-inden-1-one(BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53. Furthermore, BCI treatment increased the level of cellular reactive oxygen species and pre-treatment of cells with N-acetylcysteine markedly attenuated BCI-mediated apoptosis of NCI-H1299 cells. BCI induced cellular morphological changes, inhibited viability, and produced reactive oxygen species in NCI-H1299 cells in a dose-dependent manner. BCI induced processing of caspase-9, caspase-3, and poly ADP-ribose polymerase as well as the release of cytochrome c from the mitochondria into the cytosol. In addition, BCI downregulated Bcl-2 expression and enhanced Bax expression in a dose-dependent manner in NCI-H1299 cells. However, BCI failed to modulate the expression of the death receptor and extrinsic factor caspase-8 and Bid, a linker between the intrinsic and extrinsic apoptotic pathways in NCI-H1299 cells. Thus, BCI induces apoptosis via generation of reactive oxygen species and activation of the intrinsic pathway in NCI-H1299 cells.

关键词： non-small cell lung cancer apoptosis BCI cytotoxicity anticancer ROS

KoNA:korean Nucleotide Archive as A New Data Repository for Nucleotide Sequence Data

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 161-167页

作者： Gunhwan Ko Jae Ho Lee Young Mi Sim Wangho Song Byung-Ha Yoon Iksu Byeon Bang Hyuck Lee Sang-Ok Kim Jinhyuk Choi Insoo Jang Hyerin Kim Jin Ok Yang Kiwon Jang Sora Kim Jong-Hwan Kim Jongbum Jeon Jaeeun Jung Seungwoo Hwang Ji-Hwan Park Pan-Gyu Kim Seon-Young Kim Byungwook Lee korea Bioinformation Center Korea Research Institute of Bioscience&BiotechnologyDaejeon 34141Republic of Korea

During the last decade,the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges,including access to human data,as well as transfer,storage,and sharing of enormous amounts of *** promote data-driven biological research,the korean government announced that all biological data generated from government-funded research projects should be deposited at the korea BioData Station(K-BDS),which consists of multiple databases for individual data ***,we introduce the korean Nucleotide Archive(KoNA),a repository of nucleotide sequence *** of July 2022,the korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome *** ensure data quality and prepare for international alignment,a standard operating procedure was adopted,which is similar to that of the International Nucleotide Sequence Database *** standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline,followed by manual *** ensure fast and stable data transfer,a high-speed transmission system called GBox is used in ***,the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called *** seamless coupling of KoNA,GBox,and Bio-Express enhances the data experience,including submission,access,and analysis of raw nucleotide *** not only satisfies the unmet needs for a national sequence repository in korea but also provides datasets to researchers globally and contributes to advances in *** KoNA is available at https://***/kona/.

关键词： korea BioData Station Nucleotide sequence Next-generation sequencing repository Genomics Deposition and access of big data

Diverse Functions of VDUP1 in Cell Proliferation,Differentiation,and Diseases

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Cellular & Molecular Immunology 2007年第5期4卷 345-351页

作者： Sang Yong Kim Hyun-Woo Suh Jin Woong Chung Suk-Ran Yoon Inpyo Choi Stem Cell research Center Korea Research Institute of Bioscience and BiotechnologyYusongTaejon 305-333Republic of Korea

Vitamin D3 up-regulated protein 1 （VDUP1） is a multifunctional protein involved in maintaining cellular homeostasis. VDUP1 is induced by a variety of stresses. Inversely, VDUP1 is often reduced in various tumor tissues and cell lines. Over-expression of VDUP1 inhibits cell proliferation through cell cycle arrest. VDUP1 interacts with thioredoxin （Trx） and negatively regulates the expression and antioxidant function of Trx which is involved in redox regulation. VDUP1/ mice are more susceptible to carcinogenesis than wild-type mice and are defective in establishing immune system induding the development and function of natural killer cells. Furthermore, VDUP1^-/- mice show impaired Kreb cycle-mediated fatty acid utilization. In this review, we have discussed the multifunctional roles of VDUP1 in diverse cellular responses, in particular its relation to proliferation, apoptosis, differentiation, and diseases such as cancer and stress-related diseases.

关键词： VDUP1 thioredoxin proliferation immune cell

The role of water channel proteins and nitric oxide signaling in rice seed germination

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Cell research 2007年第7期17卷 638-649页

作者： Sang-Soo Kwak korea research institute of bioscience and biotechnology Oun-dong 52 Yusong Taejon 305-333 South korea

Previous studies have demonstrated the possible role of several aquaporins in seed germination. But systematic inves-tigation of the role of aquaporin family members in this process is lacking. Here, the developmental regulation of plasmamembrane intrinsic protein (PIP) expression throughout germination and post-germination processes in rice embryoswas analyzed. The expression patterns of the PIPs suggest these aquaporins play different roles in seed germination andseedling growth. Partial silencing of the water channel genes, OsPIP1;1 and OsPIP1;3, reduced seed germination whileover-expression of OsPIP1;3 promoted seed germination under water-stress conditions. Moreover, spatial expressionanalysis indicates that OsPIP1;3 is expressed predominantly in embryo during seed germination. Our data also revealedthat the nitric oxide (NO) donors, sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO), promoted seed germi-nation; furthermore, the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, inhibitedgermination and reduced the stimulative effects of SNP and GSNO on rice germination. Exogenous NO stimulated thetranscription of OsPIP1;1, OsPIP1;2, OsPIP1;3 and OsPIP2;8 in germinating seeds. These results suggest that waterchannels play an important role in seed germination, acting, at least partly, in response to the NO signaling pathway.

关键词： germination nitric oxide Oryza sativa over-expression silencing water channel

Rice Transcription Factor OsDOFll Modulates Sugar Transport by Promoting Expression of Sucrose Transporter and SWEET Genes

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Molecular Plant 2018年第6期11卷 833-845页

作者： Yunfei Wu Sang-Kyu Lee Youngchul Yoo Jinhuan Wei Suk-Yoon Kwon Sang-Won Lee Jong-Seong Jeon Gynheung An Crop Biotech institute and Graduate School of biotechnology Kyung Hee University Yongin 17104 Korea Plant Systems Engineering research Center Korea Research Institute of Bioscience and Biotechnology Daejeon 34141 Korea

Sucrose is produced in mesophyll cells and transferred into phloem cells before it is delivered long- distance to sink tissues. However, little is known about how sucrose transport is regulated in plants. Here, we identified a T-DNA insertional mutant of Oryza sativa DNA BINDING WITH ONE FINGER 11 （OsDOF11）, which is expressed in the vascular cells of photosynthetic organs and in various sink tissues. The osdofll mutant plants are semi-dwarf and have fewer tillers and smaller panicles as compared with wild-type （WT） plants. Although sucrose enhanced root elongation in young WT seedlings, this enhance- ment did not occur in osdof11 seedlings due to reduced sucrose uptake. Sugar transport rate analyses revealed that less sugar was transported in osdofll plants than in the WT. Expression of four Sucrose Transporter （SUT） genes-OsSUT1, OsSUT3, OsSUT4, and OsSUT5-as well as two Sugars Will Eventually be Exported Transporters （SWEET） genes, OsSWEETll and OsSWEET14, was altered in various organs of the mutant, including the leaves. Chromatin immunoprecipitation assays showed that OsDOFll directly binds the promoter regions of SUT1, OsSWEETll, and OsSWEET14, indicating that the expression of these transporters responsible for sucrose transport via apopiastic loading is coordinately controlled by OsDOFll. We also observed that osdofll mutant plants were less susceptible to infection byXanthomonas oryzae pathovar oryzae, suggesting that OsDOFll participates in sugar distribution during pathogenic in- vasion. Collectively, these results suggest that OsDOFll modulates sugar transport by regulating the expression of both SUT and SWEET genes in rice.

关键词： OsDOF11 phloem loading rice SUT SWEET Xanthomonas oryzae

Genomic and epigenomic heterogeneity in molecularsubtypes of gastric cancer

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World Journal of Gastroenterology 2016年第3期22卷 1190-1201页

作者： Byungho Lim Jong-Hwan Kim Mirang Kim Seon-Young Kim Genome Structure research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 305-806South Korea Department of Functional Genomics University of Science and TechnologyDaejeon 305-350South Korea Epigenome research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 305-806South Korea

Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.

关键词： DNA methylation Gastric cancer Molecularsubtype Mutation Next-generation sequencing

HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway

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World Journal of Gastroenterology 2010年第39期16卷 4932-4937页

作者： Hye-Lin Ha Dae-Yeul Yu Disease Model research Laboratory Aging Research CenterKorea Research Institute of Bioscience and Biotechnology Department of Functional Genomics University of Science and Technology

AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx ***:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was *** ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by *** of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing ***:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in *** ROS were detected by *** suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased *** oxidized PTEN activated the mitogenic pathway through over-activated ***,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced *** produced ROS also stimulated HBx ***:HBx induced ROS promoted Akt pathways via oxidized inactive *** and ROS maintained a positive regulatory loop,which aggravated carcinogenesis.

关键词： Hepatitis B virus X protein Hepatocellular carcinoma Akt Reactive oxygen species Phosphatase and tensin homolog

Extracellular nucleoprotein exacerbates influenza viruspathogenesis by activating Toll-like receptor 4 and the NLRP3inflammasome

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Cellular & Molecular Immunology 2022年第6期19卷 715-725页

作者： Chang-Ung Kim Yu-Jin Jeong Pureum Lee Moo-Seung Lee Jong-Hwan Park Young-Sang Kim Doo-Jin Kim Infectious Disease research Center Korea Research Institute of Bioscience and Biotechnology(KRIBB)DaejeonSouth Korea Department of Biochemistry Chungnam National UniversityDaejeonSouth Korea Environmental Diseases research Center Korea Research Institute of Bioscience and Biotechnology(KRIBB)DaejeonSouth Korea University of Science and Technology(UST) DaejeonSouth Korea College of Veterinary Medicine Chonnam National UniversityGwangjuSouth Korea

Host immune responses, such as those initiated by pattern recognition receptor (PRR) activation, are important for viralclearance and pathogenesis. However, little is known about the interactions of viral proteins with surface PRRs or, moreimportantly, the association of innate immune activation with viral pathogenesis. In this study, we showed that internalinfluenza virus proteins were released from infected cells. Among these proteins, nucleoprotein (NP) played a critical role inviral pathogenesis by stimulating neighboring cells through toll-like receptor (TLR)2, TLR4, and the NLR family pyrin domaincontaining 3 (NLRP3) inflammasome. Through the activation of these PRRs, NP induced the production of interleukin (IL)-1β andIL-6, which subsequently led to the induction of trypsin. Trypsin induced by NP increased the infectivity of influenza virus,leading to increases in viral replication and pathology upon subsequent viral infection. These results reveal the role of releasedNP in influenza pathogenesis and highlight the importance of the interactions of internal viral proteins with PRRs in theextracellular compartment during viral pathogenesis.

关键词： Influenza virus Viral protein release Nucleoprotein Toll-like receptor Cyotkine-trypsin cycle

Characterization and mapping of a novel light-dependent lesion mimic mutant lmm6 in rice(Oryza sativa L.)

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Journal of Integrative Agriculture 2015年第9期14卷 1687-1696页

作者： XIAO Gui-qing ZHANG Hai-wen LU Xiang-yang HUANG Rong-feng College of bioscience and biotechnology Hunan Agricultural University Hunan Agricultural Bioengineering research institute biotechnology research institute Chinese Academy of Agricultural Sciences

A novel rice lesion mimic mutant (LMM) was isolated from an ethane methyl sulfonate (EMS)-induced 02428 mutant bank. The mutant, tentatively designated as lmm6, develops necrotic lesions in the whole growth period along with changes in several important agronomic traits. We found that the initiation of the lesions was induced by light and cel death occurred in lmm6 accompanied with accumulation of reactive oxygen species (ROS). The lower chlorophyl content, soluble protein content and superoxide dismutase (SOD) activity, the higher malondialdehyde (MDA) content were detected in lmm6 than in the wild type (WT). Moreover, the observation by transmission electronic microscope (TEM) demonstrated that some organel es were damaged and the stroma lamel a of chloroplast was irregular and loose in mesophyl cel of lmm6. In addition, lmm6 was more resistant than WT to rice blast fungus Magnaporthe grisea infection, which was consistent with increased expression of four genes involved in the defense-related reaction. Genetic analysis showed that mutant trait of lmm6 is inherited as a monogenic recessive nuclear gene located on the long arm of chromosome 6. Using simple sequence repeat (SSR) markers, the target gene was ifnal y delimited to an interval of 80.8 kb between markers MM2359 and MM2370, containing 7 annotated genes. Taken together, our results provide the information to identify a new gene involved in rice lesion mimic, which wil be helpful in clarifying the mechanism of cel death and disease resistance in rice.

关键词： rice lesion mimic mutant gene mapping ROS blast resistance