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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
Regulation of HIF-1α stability by lysine methylation
Baek, Sung Hee ; Kim, Keun Il ;
BMB Reports , volume 49, issue 5, 2016, Pages 245~246
DOI : 10.5483/BMBRep.2016.49.5.053
The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1α
), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1α
knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1α
knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms.
New role of E3 ubiquitin ligase in the regulation of necroptosis
Seo, Jinho ; Lee, Eun-Woo ; Song, Jaewhan ;
BMB Reports , volume 49, issue 5, 2016, Pages 247~248
DOI : 10.5483/BMBRep.2016.49.5.067
Necroptosis is a well-known form of caspase-independent cell death. Necroptosis can be triggered by various extrinsic stimuli, including death ligands in the presence of receptorinteracting protein kinase 3 (RIPK3), a key mediator of necroptosis induction. Our recent studies have revealed that C-terminus HSC-70 interacting protein (CHIP), an E3 ligase, can function as an inhibitor of necroptosis. CHIP
mouse embryonic fibroblast showed higher sensitivity to necrotic stimuli than wild-type mouse embryonic fibroblast cells. Deleterious effects of CHIP knockout MEFs were retrieved by RIPK3 depletion. We found that CHIP negatively regulated RIPK3 and RIPK1 by ubiquitylation- and lysosome- dependent degradation. In addition, CHIP
mice showed postnatal lethality with intestinal defects that could be rescued by crossing with RIPK3
mice. These results suggest that CHIP is a negative regulator of RIPK1 and RIPK3, thus inhibiting necroptosis.
Spot the difference: Solving the puzzle of hidden pictures in the lizard genome for identification of regeneration factors
Chung, Jin Woong ;
BMB Reports , volume 49, issue 5, 2016, Pages 249~254
DOI : 10.5483/BMBRep.2016.49.5.045
All living things share some common life processes, such as growth and reproduction, and have the ability to respond to their environment. However, each type of organism has its own specialized way of managing biological events. Genetic sequences determine phenotypic and physiological traits. Based on genetic information, comparative genomics has been used to delineate the differences and similarities between various genomes, and significant progress has been made in understanding regenerative biology by comparing the genomes of a variety of lower animal models of regeneration, such as planaria, zebra fish, and newts. However, the genome of lizards has been relatively ignored until recently, even though lizards have been studied as an excellent amniote model of tissue regeneration. Very recently, whole genome sequences of lizards have been uncovered, and several attempts have been made to find regeneration factors based on genetic information. In this article, recent advances in comparative analysis of the lizard genome are introduced, and their biological implications and putative applications for regenerative medicine and stem cell biology are discussed.
Introduction to cerebral cavernous malformation: a brief review
Kim, Jaehong ;
BMB Reports , volume 49, issue 5, 2016, Pages 255~262
DOI : 10.5483/BMBRep.2016.49.5.036
The disease known as cerebral cavernous malformations mostly occurs in the central nervous system, and their typical histological presentations are multiple lumen formation and vascular leakage at the brain capillary level, resulting in disruption of the blood-brain barrier. These abnormalities result in severe neurological symptoms such as seizures, focal neurological deficits and hemorrhagic strokes. CCM research has identified `loss of function` mutations of three ccm genes responsible for the disease and also complex regulation of multiple signaling pathways including the WNT/β-catenin pathway, TGF-β and Notch signaling by the ccm genes. Although CCM research is a relatively new and small scientific field, as CCM research has the potential to regulate systemic blood vessel permeability and angiogenesis including that of the blood-brain barrier, this field is growing rapidly. In this review, I will provide a brief overview of CCM pathogenesis and function of ccm genes based on recent progress in CCM research.
MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation
Lee, Juneyoung ; Park, Eun Jeong ; Kiyono, Hiroshi ;
BMB Reports , volume 49, issue 5, 2016, Pages 263~269
DOI : 10.5483/BMBRep.2016.49.5.041
The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation.
Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells
Lee, Hyunjung ; Park, Jinyoung ; Kim, Eunice EunKyeong ; Yoo, Young Sook ; Song, Eun Joo ;
BMB Reports , volume 49, issue 5, 2016, Pages 270~275
DOI : 10.5483/BMBRep.2016.49.5.187
The Ubiquitin proteasome system (UPS) plays roles in protein degradation, cell cycle control, and growth and inflammatory cell signaling. Dysfunction of UPS in cardiac diseases has been seen in many studies. Cholesterol acts as an inducer of cardiac hypertrophy. In this study, the effect of proteasome inhibitors on the cholesterol-induced hypertrophic growth in H9c2 cells is examined in order to observe whether UPS is involved in cardiac hypertrophy. The treatment of proteasome inhibitors MG132 and Bortezomib markedly reduced cellular surface area and mRNA expression of β-MHC in cholesterol-induced cardiac hypertrophy. In addition, activated AKT and ERK were significantly attenuated by MG132 and Bortezomib in cholesterol-induced cardiac hypertrophy. We demonstrated that cholesterol-induced cardiac hypertrophy was suppressed by proteasome inhibitors. Thus, regulatory mechanism of cholesterol-induced cardiac hypertrophy by proteasome inhibitors may provide a new therapeutic strategy to prevent the progression of heart failure.
Corosolic acid ameliorates acute inflammation through inhibition of IRAK-1 phosphorylation in macrophages
Kim, Seung-Jae ; Cha, Ji-Young ; Kang, Hye Suk ; Lee, Jae-Ho ; Lee, Ji Yoon ; Park, Jae-Hyung ; Bae, Jae-Hoon ; Song, Dae-Kyu ; Im, Seung-Soon ;
BMB Reports , volume 49, issue 5, 2016, Pages 276~281
DOI : 10.5483/BMBRep.2016.49.5.241
Corosolic acid (CA), a triterpenoid compound isolated from Lagerstroemia speciosa L. (Banaba) leaves, exerts anti-inflammatory effects by regulating phosphorylation of interleukin receptor- associated kinase (IRAK)-2 via the NF-κB cascade. However, the protective effect of CA against endotoxic shock has not been reported. LPS (200 ng/mL, 30 min) induced phosphorylation of IRAK-1 and treatment with CA (10 μM) significantly attenuated this effect. In addition, CA also reduced protein levels of NLRP3 and ASC which are the main components of the inflammasome in BMDMs. LPS-induced inflammasome assembly through activation of IRAK-1 was down-regulated by CA challenge. Treatment with Bay11-7082, an inhibitor of IκB-α, had no effect on CA-mediated inhibition of IRAK-1 activation, indicating that CA-mediated attenuation of IRAK-1 phosphorylation was independent of NF-κB signaling. These results demonstrate that CA ameliorates acute inflammation in mouse BMDMs and CA may be useful as a pharmacological agent to prevent acute inflammation.
Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif
Han, Ji Hye ; Moon, Ae Ran ; Chang, Jeong Hwan ; Bae, Jeehyeon ; Choi, Jin Myung ; Lee, Sung Haeng ; Kim, Tae-Hyoung ;
BMB Reports , volume 49, issue 5, 2016, Pages 282~287
DOI : 10.5483/BMBRep.2016.49.5.245
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a homo-trimeric cytotoxic ligand. Several studies have demonstrated that incorporation of artificial trimerization motifs into the TRAIL protein leads to the enhancement of biological activity. Here, we show that linkage of the isoleucine zipper hexamerization motif to the N-terminus of TRAIL, referred as ILz(6):TRAIL, leads to multimerization of its trimeric form, which has higher cytotoxic activity compared to its native state. Size exclusion chromatography of ILz(6):TRAIL revealed possible existence of various forms such as trimeric, hexameric, and multimeric (possibly containing one-, two-, and multi-units of trimeric TRAIL, respectively). Increased number of multimerized ILz(6):TRAIL units corresponded with enhanced cytotoxic activity. Further, a high degree of ILz(6):TRAIL multimerization triggered rapid signaling events such as activation of caspases, tBid generation, and chromatin condensation. Taken together, these results indicate that multimerization of TRAIL significantly enhances its cytotoxic activity.
Neuropeptide Y protects kidney against cisplatin-induced nephrotoxicity by regulating p53-dependent apoptosis pathway
Kim, Namoh ; Min, Woo-Kie ; Park, Min Hee ; Lee, Jong Kil ; Jin, Hee Kyung ; Bae, Jae-sung ;
BMB Reports , volume 49, issue 5, 2016, Pages 288~292
DOI : 10.5483/BMBRep.2016.49.5.231
Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy-induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity.
A novel IL-10-producing innate lymphoid cells (ILC10) in a contact hypersensitivity mouse model
Kim, Hyuk Soon ; Jang, Jong-Hwa ; Lee, Min Bum ; Jung, In Duk ; Park, Yeong-Min ; Kim, Young Mi ; Choi, Wahn Soo ;
BMB Reports , volume 49, issue 5, 2016, Pages 293~296
DOI : 10.5483/BMBRep.2016.49.5.023
The immunoregulatory cytokine Interleukin 10 (IL-10) protein is produced by various cells during the course of inflammatory disorders. Mainly, it downregulates pro-inflammatory cytokines, antigen presentation, and helper T cell activation. In this study, we show that the ratio of IL-10-producing cells was significantly increased in lineage negative (i.e., not T, B, or leukocyte cell lineages) cells than in lineage positive cells in lymphoid and peripheral tissues. We further observed that IL-10-producing innate lymphoid cells (ILCs), here called firstly ILC10, were increased in number in oxazolone-induced contact hypersensitivity (CHS) mice. In detail, IL-10-producing lineage negative cells were elevated in the axillary, inguinal lymph node, and ear tissues of CHS mice. Notably, the cells expressed classical ILC marker proteins such as CD45, CD127, and Sca-1. Altogether, our findings suggest for the first time that ILC10s are present in various physiological settings and could be involved in numerous immune responses as regulatory cells.
Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death
Jo, Hyo Sang ; Yeo, Hyeon Ji ; Cha, Hyun Ju ; Kim, Sang Jin ; Cho, Su Bin ; Park, Jung Hwan ; Lee, Chi Hern ; Yeo, Eun Ji ; Choi, Yeon Joo ; Eum, Won Sik ; Choi, Soo Young ;
BMB Reports , volume 49, issue 5, 2016, Pages 297~302
DOI : 10.5483/BMBRep.2016.49.5.058
Loss of pancreatic β-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1β, IFN-γ and TNF-α)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines-induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine-induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases.