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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
Korean Society for Biochemistry and Molecular Biology
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Volume & Issues
Volume 49, Issue 9 - Sep 2016
Volume 49, Issue 8 - Aug 2016
Volume 49, Issue 7 - Jul 2016
Volume 49, Issue 6 - Jun 2016
Volume 49, Issue 5 - May 2016
Volume 49, Issue 4 - Apr 2016
Volume 49, Issue 3 - Mar 2016
Volume 49, Issue 2 - Feb 2016
Volume 49, Issue 1 - Jan 2016
Selecting the target year
An efficient SCNT technology for the establishment of personalized and public human pluripotent stem cell banks
Lee, Jeoung Eun ; Chung, Young Gie ; Eum, Jin Hee ; Lee, Yumie ; Lee, Dong Ryul ;
BMB Reports , volume 49, issue 4, 2016, Pages 197~198
DOI : 10.5483/BMBRep.2016.49.4.055
Although three different research groups have reported successful derivations of human somatic cell nuclear transfer-derived embryonic stem cell (SCNT-ESC) lines using fetal, neonatal and adult fibroblasts, the extremely poor development of cloned embryos has hindered its potential applications in regenerative medicine. Recently, however, our group discovered that the severe methylation of lysine 9 in Histone H3 in a human somatic cell genome was a major SCNT reprogramming barrier, and the overexpression of KDM4A, a H3K9me3 demethylase, significantly improved the blastocyst formation of SCNT embryos. In particular, by applying this new approach, we were able to produce multiple SCNT-ES cell lines using oocytes obtained from donors whose eggs previously failed to develop to the blastocyst stage. Moreover, the success rate was closer to 25%, which is comparable to that of IVF embryos, so that our new human SCNT method seems to be a practical approach to establishing a pluripotent stem cell bank for the general public as well as for individual patients.
Gene repressive mechanisms in the mouse brain involved in memory formation
Yu, Nam-Kyung ; Kaang, Bong-Kiun ;
BMB Reports , volume 49, issue 4, 2016, Pages 199~200
DOI : 10.5483/BMBRep.2016.49.4.044
Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls.
Structural and dynamic views of the CRISPR-Cas system at the single-molecule level
Lee, Seung Hwan ; Bae, Sangsu ;
BMB Reports , volume 49, issue 4, 2016, Pages 201~207
DOI : 10.5483/BMBRep.2016.49.4.042
The CRISPR-Cas system has emerged as a fascinating and important genome editing tool. It is now widely used in biology, biotechnology, and biomedical research in both academic and industrial settings. To improve the specificity and efficiency of Cas nucleases and to extend the applications of these systems for other areas of research, an understanding of their precise working mechanisms is crucial. In this review, we summarize current studies on the molecular structures and dynamic functions of type I and type II Cas nucleases, with a focus on target DNA searching and cleavage processes as revealed by single-molecule observations.
miR-185 inhibits endoplasmic reticulum stress-induced apoptosis by targeting Na
exchanger-1 in the heart
Kim, Jin Ock ; Kwon, Eun Jeong ; Song, Dong Woo ; Lee, Jong Sub ; Kim, Do Han ;
BMB Reports , volume 49, issue 4, 2016, Pages 208~213
DOI : 10.5483/BMBRep.2016.49.4.193
Prolonged ER stress (ERS) can be associated with the induction of apoptotic cell death in various heart diseases. In this study, we searched for microRNAs affecting ERS in the heart using in silico and in vitro methods. We found that miR-185 directly targets the 3′-untranslated region of Na
exchanger-1 (NHE-1), a protein involved in ERS. Cardiomyocyte ERS-triggered apoptosis induced by 100 ng/ml tunicamycin (TM) or 1 μM thapsigargin (TG), ERS inducers, was significantly reduced by miR-185 overexpression. Protein expression of pro-apoptotic markers such as CCAAT/enhancer-binding protein homologous protein (CHOP) and cleaved-caspase-3 was also markedly reduced by miR-185 in a dose-dependent manner. Cariporide (20 μM), a pharmacological inhibitor of NHE-1, also attenuated ERS-induced apoptosis in cardiomyocytes and CHOP protein expression, suggesting that NHE-1 plays an important role in ERS-associated apoptosis in cardiomyocytes. Collectively, the present results demonstrate that miR-185 is involved in cardio-protection against ERS-mediated apoptotic cell death.
Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses
Jung, Byeongjin ; Kang, Hyejin ; Lee, Wonhwa ; Noh, Hyun Jin ; Kim, You-Sun ; Han, Min-Su ; Baek, Moon-Chang ; Kim, Jaehong ; Bae, Jong-Sup ;
BMB Reports , volume 49, issue 4, 2016, Pages 214~219
DOI : 10.5483/BMBRep.2016.49.4.220
A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway.
Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells
Joo, Donghyun ; Woo, Jong Soo ; Cho, Kwang-Hyun ; Han, Seung Hyun ; Min, Tae Sun ; Yang, Deok-Chun ; Yun, Cheol-Heui ;
BMB Reports , volume 49, issue 4, 2016, Pages 220~225
DOI : 10.5483/BMBRep.2016.49.4.004
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.
Targeted disruption of EBNA1 in EBV-infected cells attenuated cell growth
Noh, Ka-Won ; Park, Jihyun ; Kang, Myung-Soo ;
BMB Reports , volume 49, issue 4, 2016, Pages 226~231
DOI : 10.5483/BMBRep.2016.49.4.260
Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt`s lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter-selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders.
Anti-inflammatory action of ethanolic extract of Ramulus mori on the BLT2-linked cascade
Park, Geun-Soo ; Kim, Jeong-Keun ; Kim, Jae-Hong ;
BMB Reports , volume 49, issue 4, 2016, Pages 232~237
DOI : 10.5483/BMBRep.2016.49.4.002
Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti-inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL-6 production by blocking the leukotriene B
receptor-2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti-inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase-cytosolic phospholipase A
-5-/12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the `BLT2 ligand-BLT2`-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti-inflammatory action of R. mori.
SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy
Na, Han-Heom ; Noh, Hee-Jung ; Cheong, Hyang-Min ; Kang, Yoonsung ; Kim, Keun-Cheol ;
BMB Reports , volume 49, issue 4, 2016, Pages 238~243
DOI : 10.5483/BMBRep.2016.49.4.031
The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy.