The caspase-8/Bid/cytochrome <i>c</i> axis links signals from death receptors to mitochondrial reactive oxygen species production

Kim, Wan-Sung,Lee, Kwang-Soon,Kim, Ji-Hee,Kim, Chun-Ki,Lee, Gwangsoo,Choe, Jongseon,Won, Moo-Ho,Kim, Tae-Hyoung,Jeoung, Dooil,Lee, Hansoo,Kim, Ji-Yoon,Ae Jeong, Mi,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Y PERGAMON PRESS 2017 FREE RADICAL BIOLOGY AND MEDICINE Vol.112 No.-

<P><B>Abstract</B></P> <P>Ligation of the death receptors for TNF-α, FasL, and TRAIL triggers two common pathways, caspase-dependent intrinsic apoptosis and intracellular reactive oxygen species (ROS) generation. The apoptotic pathway is well characterized; however, a signaling linker between the death receptor and ROS production has not been clearly elucidated. Here, we found that death receptor-induced ROS generation was strongly inhibited by mitochondrial complex I and II inhibitors, but not by inhibitors of NADPH oxidase, lipoxygenase, cyclooxygenase or xanthine oxidase, indicating that ROS are mostly generated by the impairment of the mitochondrial respiratory chain. ROS generation was accompanied by caspase-8 activation, Bid cleavage, and cytochrome <I>c</I> release; it was blocked in FADD- and caspase-8-deficient cells, as well as by caspase-8 knockdown and inhibitor. Moreover, Bid knockdown abrogated TNF-α- or TRAIL-induced ROS generation, whereas overexpression of truncated Bid (tBid) or knockdown of cytochrome <I>c</I> spontaneously elevated ROS production. In addition, p53-overexpressing cells accumulated intracellular ROS via cytochrome <I>c</I> release mediated by the BH3-only protein Noxa induction. In a cell-free reconstitution system, caspase-8-mediated Bid cleavage and recombinant tBid induced mitochondrial cytochrome <I>c</I> release and ROS generation, which were blocked by Bcl-xL and antioxidant enzymes. These data suggest that anti-apoptotic Bcl-2 proteins play an important role in mitochondrial ROS generation by preventing cytochrome <I>c</I> release. These data provide evidence that the FADD/caspase-8/Bid/cytochrome <I>c</I> axis is a crucial linker between death receptors and mitochondria, where they play a role in ROS generation and apoptosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Death receptor ligands produce mitochondrial ROS (mROS) in a caspase-8-dependent manner. </LI> <LI> mROS production requires tBid formation and cytochrome <I>c</I> release. </LI> <LI> The caspase-8/Bid/cytochrome <I>c</I> axis plays a key role in death receptor-mediated mROS generation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

프라이버시 보호 데이터 배포를 위한 모델 조사

김종선(Jongseon Kim),정기정(Kijung Jung),이혁기(Hyukki Lee),김수형(Soohyung Kim),김종욱(Jong Wook Kim),정연돈(Yon Dohn Chung) 한국정보과학회 2017 정보과학회논문지 Vol.44 No.2

최근 다양한 분야에서 데이터들이 활발하게 활용되고 있다. 이에 따라 데이터의 공유나 배포를 요구하는 목소리가 높아지고 있다. 그러나 공유된 데이터에 개인과 관련된 민감한 정보가 있을 경우, 개인의 민감한 정보가 드러나는 프라이버시 유출이 발생할 수 있다. 개인 정보가 포함된 데이터를 배포하기 위해 개인의 프라이버시를 보호하면서 데이터를 최소한으로 변형하는 프라이버시 보호 데이터 배포(privacy-preserving data publishing, PPDP)가 연구되어 왔다. 프라이버시 보호 데이터 배포 연구는 다양한 공격자 모델을 가정하고 이러한 공격자의 프라이버시 유출 공격으로부터 프라이버시를 보호하기 위한 원칙인 프라이버시 모델에 따라 발전해왔다. 본 논문에서는 먼저 프라이버시 유출 공격에 대해 알아본다. 그리고 프라이버시 모델들을 프라이버시 유출 공격에 따라 분류하고 각 프라이버시 모델들 간의 차이점과 요구 조건에 대해 알아본다. In recent years, data are actively exploited in various fields. Hence, there is a strong demand for sharing and publishing data. However, sensitive information regarding people can breach the privacy of an individual. To publish data while protecting an individual’s privacy with minimal information distortion, the privacy- preserving data publishing(PPDP) has been explored. PPDP assumes various attacker models and has been developed according to privacy models which are principles to protect against privacy breaching attacks. In this paper, we first present the concept of privacy breaching attacks. Subsequently, we classify the privacy models according to the privacy breaching attacks. We further clarify the differences and requirements of each privacy model.

miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Kim, Youngmi,Kim, Hyuna,Park, Hyunmi,Park, Deokbum,Lee, Hansoo,Lee, Yun Sil,Choe, Jongseon,Kim, Young Myeong,Jeoung, Dooil American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.40

<P>Histone modification is known to be associated with multidrug resistance phenotypes. Cancer cell lines that are resistant or have been made resistant to anti-cancer drugs showed lower expression levels of histone deacetylase-3 (HDAC3), among the histone deacetylase(s), than cancer cell lines that were sensitive to anti-cancer drugs. Celastrol and Taxol decreased the expression of HDAC3 in cancer cell lines sensitive to anti-cancer drugs. HDAC3 negatively regulated the invasion, migration, and anchorage-independent growth of cancer cells. HDAC3 conferred sensitivity to anti-cancer drugs <I>in vitro</I> and <I>in vivo</I>. TargetScan analysis predicted <I>miR-326</I> as a negative regulator of HDAC3. ChIP assays and luciferase assays showed a negative feedback loop between HDAC3 and <I>miR-326. miR-326</I> decreased the apoptotic effect of anti-cancer drugs, and the <I>miR-326</I> inhibitor increased the apoptotic effect of anti-cancer drugs. <I>miR-326</I> enhanced the invasion and migration potential of cancer cells. The <I>miR-326</I> inhibitor negatively regulated the tumorigenic, metastatic, and angiogenic potential of anti-cancer drug-resistant cancer cells. HDAC3 showed a positive feedback loop with miRNAs such as <I>miR-200b</I>, <I>miR-217</I>, and <I>miR-335. miR-200b</I>, <I>miR-217</I>, and <I>miR-335</I> negatively regulated the expression of <I>miR-326</I> and the invasion and migration potential of cancer cells while enhancing the apoptotic effect of anti-cancer drugs. TargetScan analysis predicted <I>miR-200b</I> and <I>miR-217</I> as negative regulators of cancer-associated gene, a cancer/testis antigen, which is known to regulate the response to anti-cancer drugs. HDAC3 and <I>miR-326</I> acted upstream of the cancer-associated gene. Thus, we show that the miR-326-HDAC3 feedback loop can be employed as a target for the development of anti-cancer therapeutics.</P>

TC1(C8orf4) is upregulated by IL-1β/TNF-α and enhances proliferation of human follicular dendritic cells

Kim, Youngmi,Kim, Jungtae,Park, Juhee,Bang, Seunghyun,Jung, Yusun,Choe, Jongseon,Song, Kyuyoung,Lee, Inchul Elsevier 2006 FEBS letters Vol.580 No.14

<P><B>Abstract</B></P><P>Follicular dendritic cells (FDC) play crucial roles in immune regulation. TNF-α has been shown to be essential to the FDC network. However, the molecular regulation of FDC proliferation has not been characterized. Here, we show that TC1(C8orf4), a novel positive regulator of the Wnt/β-catenin pathway in vertebrates, is upregulated by IL-1β and TNF-α in the human FDC-like line HK. TC1 enhances HK cell proliferation, while TC1-knockdown inhibits the proliferation induced by IL-1β, suggesting a role of TC1 as a regulator of FDC proliferation. The regulation by pro-inflammatory cytokines suggests that TC1 might be implicated in linking local inflammation to immune response by stimulating FDC.</P>

Modeling and Analysis of Floating-Poing Quantization Effects in M-Band Subband Codec

Jongseon Kim,Kyusik Park,Jaehyun Park,Heonwook Kim 대한전자공학회 1994 대한전자공학회 학술대회 Vol.1994 No.11

Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia

Kim, Joohwan,Lee, Kyu-Sun,Kim, Ji-Hee,Lee, Dong-Keon,Park, Minsik,Choi, Seunghwan,Park, Wonjin,Kim, Suji,Choi, Yoon Kyung,Hwang, Jong Yun,Choe, Jongseon,Won, Moo-Ho,Jeoung, Dooil,Lee, Hansoo,Ryoo, Sun PERGAMON PRESS 2017 FREE RADICAL BIOLOGY AND MEDICINE Vol.104 No.-

<P><B>Abstract</B></P> <P>Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, <I>microRNA (miR)−155</I>, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia. Aspirin prevented the TNF-α-mediated increase in <I>miR-155</I> biogenesis and decreases in eNOS expression and NO/cGMP production in cultured human umbilical vein endothelial cells (HUVECs). Similar effects of aspirin were also observed in HUVECs treated with H<SUB>2</SUB>O<SUB>2</SUB>. The preventive effects of aspirin was associated with the inhibition of nuclear factor-κB (NF-κB)-dependent <I>MIR155HG</I> (<I>miR-155</I> host gene<B>)</B> expression. Aspirin recovered the TNF-α-mediated decrease in wild-type, but not mutant, eNOS 3′-untranslated region reporter activity, whose effect was blocked by miR-155 mimic. Moreover, aspirin prevented TNF-α-mediated endothelial cell dysfunction associated with impaired vasorelaxation, angiogenesis, and trophoblast invasion, and the preventive effects were blocked by miR-155 mimic or an eNOS inhibitor. Aspirin rescued TNF-α-mediated eNOS downregulation coupled with endothelial dysfunction by inhibiting NF-κB-dependent transcriptional <I>miR-155</I> biogenesis. Thus, the redox-sensitive NF-κB/<I>miR-155</I>/eNOS axis may be crucial in the pathogenesis of vascular disorders including preeclampsia.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α, <I>miR-155</I>, and eNOS are differentially regulated in preeclamptic patients. </LI> <LI> Aspirin prevents TNF-α-mediated <I>miR-155</I> biogenesis and eNOS downregulation. </LI> <LI> Aspirin preserves vascular function by blocking NF-kB-mediated eNOS downregulation. </LI> <LI> Thus, the NF-kB/<I>miR-155</I>/eNOS pathway is crucial for the pathogenesis of preeclampsia. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

miR-200b and Cancer/Testis Antigen CAGE Form a Feedback Loop to Regulate the Invasion and Tumorigenic and Angiogenic Responses of a Cancer Cell Line to Microtubule-targeting Drugs

Kim, Youngmi,Park, Deokbum,Kim, Hyuna,Choi, Munseon,Lee, Hansoo,Lee, Yun Sil,Choe, Jongseon,Kim, Young Myeong,Jeoung, Dooil American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.51

<P>Cancer/testis antigen <U>ca</U>ncer-associated <U>ge</U>ne (CAGE) is known to be involved in various cellular processes, such as proliferation, cell motility, and anti-cancer drug resistance. However, the mechanism of the expression regulation of CAGE remains unknown. Target scan analysis predicted the binding of microRNA-200b (miR-200b) to CAGE promoter sequences. The expression of CAGE showed an inverse relationship with miR-200b in various cancer cell lines. miR-200b was shown to bind to the 3′-UTR of CAGE and to regulate the expression of CAGE at the transcriptional level. miR-200b also enhanced the sensitivities to microtubule-targeting drugs <I>in vitro</I>. miR-200b and CAGE showed opposite regulations on invasion potential and responses to microtubule-targeting drugs. Xenograft experiments showed that miR-200b had negative effects on the tumorigenic and metastatic potential of cancer cells. The effect of miR-200b on metastatic potential involved the expression regulation of CAGE by miR-200b. miR-200b decreased the tumorigenic potential of a cancer cell line resistant to microtubule-targeting drugs in a manner associated with the down-regulation of CAGE. ChIP assays showed the direct regulation of miR-200b by CAGE. CAGE enhanced the invasion potential of a cancer cell line stably expressing miR-200b. miR-200b exerted a negative regulation on tumor-induced angiogenesis. The down-regulation of CAGE led to the decreased expression of plasminogen activator inhibitor-1, a TGFβ-responsive protein involved in angiogenesis, and VEGF. CAGE mediated tumor-induced angiogenesis and was necessary for VEGF-promoted angiogenesis. Human recombinant CAGE protein displayed angiogenic potential. Thus, miR-200b and CAGE form a feedback regulatory loop and regulate the response to microtubule-targeting drugs, as well as the invasion, tumorigenic potential, and angiogenic potential.</P>

Transglutaminase II interacts with rac1, regulates production of reactive oxygen species, expression of snail, secretion of Th2 cytokines and mediates <i>in vitro</i> and <i>in vivo</i> allergic inflammation

Kim, Youngmi,Eom, Sangkyung,Kim, Kyungjong,Lee, Yun-Sil,Choe, Jongseon,Hahn, Jang Hee,Lee, Hansoo,Kim, Young-Myeong,Ha, Kwon Soo,Ro, Jai Youl,Jeoung, Dooil Elsevier 2010 Molecular immunology Vol.47 No.5

<P><B>Abstract</B></P><P>Transglutaminase II (TGase II) is a protein cross-linking enzyme with diverse biological functions. Here we report the role of TGase II in allergic inflammation. Antigen stimulation induced expression and activity of TGase II by activation of NF-κB in rat basophilic leukemia (RBL2H3) cells. This induction of TGase II was dependent on FcϵRI and EGFR. Interaction between TGase II and rac1 was induced following antigen stimulation. TGase II was responsible for the increased production of reactive oxygen species, expression of prostaglandin E2 synthase (PGE2 synthase) and was responsible for increased secretion of prostaglandin E2. ChIP assay showed that TGase II, through interaction with NF-κB, was responsible for the induction of histone deacetylase-3 (HDAC3) and snail by direct binding to promoter sequences. HDAC3 and snail induced by TGase II, exerted transcriptional repression on E-cadherin. Snail exerted negative effect on expression of MMP-2, and secretion of Th2 cytokines. Inhibition of matrix metalloproteinase-2 (MMP-2) inhibited secretion of Th2 cytokines. <I>In vivo</I> induction of TGase II was observed in Balb/c mouse model of IgE antibody-induced passive cutaneous anaphylaxis. Chemical inhibition of TGase II exerted negative effect on IgE-dependent passive cutaneous anaphylaxis. Chemical inhibition of TGase II by cystamine exerted negative effect on Balb/c mouse model of phorbol myristate acetate (PMA)-induced atopic dermatitis. These results suggest novel role of TGase II in allergic inflammation and TGase II can be developed as target for the development of allergy therapeutics.</P>

Histone Deacetylase 3 Mediates Allergic Skin Inflammation by Regulating Expression of MCP1 Protein

Kim, Youngmi,Kim, Kyungjong,Park, Deokbum,Lee, Eunmi,Lee, Hansoo,Lee, Yun-Sil,Choe, Jongseon,Jeoung, Dooil American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.31

Activated human B cells stimulate COX-2 expression in follicular dendritic cell-like cells via TNF-α

Kim, Jini,Lee, Seungkoo,Jeoung, Dooil,Kim, Young-Myeong,Choe, Jongseon Elsevier 2018 Molecular immunology Vol.94 No.-

<P>In spite of the potential importance of cyclooxygenase (COX)-2 expression in the germinal center, its underlying cellular and molecular mechanisms are largely unknown. COX-2 is the key enzyme generating pleiotropic prostaglandins. Based on our previous findings, we hypothesized that lymphocytes would stimulate COX-2 expression in follicular dendritic cell (FDC) by liberating cytokines. In this study, we examined the effect of tonsillar lymphocytes on COX-2 expression in FDC-like cells by immunoblotting. B but not T cells induced COX-2 protein in a time- and dose-dependent manner. Sub-fractionation analysis of B cell subsets revealed that activated but not resting B cells were responsible for the COX-2 induction. Confocal microscopy of frozen tonsils demonstrated that FDCs indeed express COX-2 in situ, in line with the in vitro results. To identify the stimulating molecule, we added neutralizing antibodies to the coculture of FDC-like cells and B cells. COX-2 induction in FDC-like cells was markedly inhibited by TNF-alpha neutralizing antibody. Finally, the actual production of TNF-alpha by activated B cells was confirmed by an enzyme immunoassay. The current study implies an unrecognized cellular interaction between FDC and B cells leading to COX-2 expression during immune inflammatory responses.</P>