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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 47, Issue 12 - Dec 2014
Volume 47, Issue 11 - Nov 2014
Volume 47, Issue 10 - Oct 2014
Volume 47, Issue 9 - Sep 2014
Volume 47, Issue 8 - Aug 2014
Volume 47, Issue 7 - Jul 2014
Volume 47, Issue 6 - Jun 2014
Volume 47, Issue 5 - May 2014
Volume 47, Issue 4 - Apr 2014
Volume 47, Issue 3 - Mar 2014
Volume 47, Issue 2 - Feb 2014
Volume 47, Issue 1 - Jan 2014
Selecting the target year
MicroRNA-directed cleavage of targets: mechanism and experimental approaches
Park, June Hyun ; Shin, Chanseok ;
BMB Reports , volume 47, issue 8, 2014, Pages 417~423
DOI : 10.5483/BMBRep.2014.47.8.109
MicroRNAs (miRNAs) are a large family of post-transcriptional regulators, which are 21-24 nt in length and play a role in a wide variety of biological processes in eukaryotes. The past few years have seen rapid progress in our understanding of miRNA biogenesis and the mechanism of action, which commonly entails a combination of target degradation and translational repression. The target degradation mediated by Argonaute-catalyzed endonucleolytic cleavage exerts a significant repressive effect on target mRNA expression, particularly during rapid developmental transitions. This review outlines the current understanding of the mechanistic aspects of this important process and discusses several different experimental approaches to identify miRNA cleavage targets.
Poly (ADP-ribose) in the pathogenesis of Parkinson's disease
Lee, Yunjong ; Kang, Ho Chul ; Lee, Byoung Dae ; Lee, Yun-Il ; Kim, Young Pil ; Shin, Joo-Ho ;
BMB Reports , volume 47, issue 8, 2014, Pages 424~432
DOI : 10.5483/BMBRep.2014.47.8.119
The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.
Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells
Kim, Young-Sang ; Li, Xi-Feng ; Kang, Kyong-Hwa ; Ryu, BoMi ; Kim, Se Kwon ;
BMB Reports , volume 47, issue 8, 2014, Pages 433~438
DOI : 10.5483/BMBRep.2014.47.8.153
Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.
AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells
Im, Jin Young ; Min, Woo-Kie ; Park, Min Hee ; Kim, NamOh ; Lee, Jong Kil ; Jin, Hee Kyung ; Choi, Je-Yong ; Kim, Shin-Yoon ; Bae, Jae-Sung ;
BMB Reports , volume 47, issue 8, 2014, Pages 439~444
DOI : 10.5483/BMBRep.2014.47.8.159
Inhibition of an increase of osteoclasts has become the most important treatment for osteoporosis. The CXCR4 antagonist, AMD3100, plays an important role in the mobilization of osteoclast precursors within bone marrow (BM). However, the actual therapeutic impact of AMD3100 in osteoporosis has not yet been ascertained. Here we demonstrate the therapeutic effect of AMD3100 in the treatment of ovariectomy-induced osteoporosis in mice. We found that treatment with AMD3100 resulted in direct induction of release of SDF-1 from BM to blood and mobilization of hematopoietic stem/progenitor cells (HSPCs) in an osteoporosis model. AMD3100 prevented bone density loss after ovariectomy by mobilization of HSPCs, suggesting a therapeutic strategy to reduce the number of osteoclasts on bone surfaces. These findings support the hypothesis that treatment with AMD3100 can result in efficient mobilization of HSPCs into blood through direct blockade of the SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis.
Glucose regulated protein 78 promotes cell invasion via regulation of uPA production and secretion in colon cancer cells
Li, Zongwei ; Zhang, Lichao ; Li, Hanqing ; Shan, Shuhua ; Li, Zhuoyu ;
BMB Reports , volume 47, issue 8, 2014, Pages 445~450
DOI : 10.5483/BMBRep.2014.47.8.211
Glucose regulated protein 78 (GRP78) is frequently highly expressed in tumor cells, contributing to the acquisition of several phenotypic cancer hallmarks. GRP78 expression is also positively correlated with tumor metastasis, and promotes hepatocellular carcinoma cell invasion via increasing cell motility, however, other mechanisms involving the prometastatic roles of GRP78 remain to be elucidated. Here we report that forced GRP78 expression promotes colon cancer cell migration and invasion through upregulating MMP-2, MMP-9 and especially uPA production. These effects of GRP78 are mediated by enhancing the activation of
-catenin signaling. Interestingly, we identify that GRP78 interacts with uPA both in the cells and in the culture medium, suggesting that GRP78 protein is likely to directly facilitate uPA secretion via protein-protein interaction. Taken together, our findings demonstrate for the first time that besides stimulation of cell motility, GRP78 can act by increasing proteases production to promote tumor cell invasion.
Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis
Kim, Ju-Young ; Cheon, Yoon-Hee ; Yoon, Kwon-Ha ; Lee, Myeung Su ; Oh, Jaemin ;
BMB Reports , volume 47, issue 8, 2014, Pages 451~456
DOI : 10.5483/BMBRep.2014.47.8.206
Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of
ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and
, as well as
degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.
The expression and secretion of vimentin in the progression of non-alcoholic steatohepatitis
Lee, Su Jin ; Yoo, Jae Do ; Choi, Soo Young ; Kwon, Oh-Shin ;
BMB Reports , volume 47, issue 8, 2014, Pages 457~462
DOI : 10.5483/BMBRep.2014.47.8.256
The pathogenesis of non-alcoholic steatohepatitis (NASH) is not fully understood. In the present study, both in vitro and in vivo vimentin expression and secretion in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS) to HepG2 cells enhanced caspase-3 activity and vimentin expression, respectively. The combined effects of both treatments on vimentin expression and caspase-3 activation appeared to be synergic. In contrast, blockade of caspase-3 activity by zVADfmk resulted in a significant reduction of cleaved vimentin and secreted vimentin into the culture supernatant. Similarly, lipid accumulation and inflammation occurred in mice fed a methionine-choline-deficient diet; thus, vimentin expression and serum cleaved vimentin levels were increased. However, vimentin was not significantly upregulated, and no cleavage occurred in mice fed a high-fat diet. It was conclusively determined that lipid accumulation in hepatocytes induces apoptosis through a caspase-3 dependent pathway; whereas, LPS stimulates vimentin expression, leading to its cleavage and secretion. Increased vimentin fragment levels indicated the existence of substantial hepatocellular death via an apoptotic mechanism.
GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2
Song, Insun ; Kim, Kabsun ; Kim, Jung Ha ; Lee, Young-Kyoung ; Jung, Hyun-Jung ; Byun, Hae-Ok ; Yoon, Gyesoon ; Kim, Nacksung ;
BMB Reports , volume 47, issue 8, 2014, Pages 463~468
DOI : 10.5483/BMBRep.2014.47.8.225
Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteogenic conditioned cell culture system. In addition, overexpression of GATA4 attenuated expression of osteogenic marker genes, including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of which are important for osteoblast differentiation and function. Overexpression of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that GATA4 acts as a negative regulator in osteoblast differentiation by downregulation of Runx2.
Global knockdown of microRNAs affects the expression of growth factors and cytokines in human adipose-derived mesenchymal stem cells
Park, Seul-Ki ; Lee, Jung Shin ; Choi, Eun Kyung ; You, Dalsan ; Kim, Choung-Soo ; Suh, Nayoung ;
BMB Reports , volume 47, issue 8, 2014, Pages 469~474
DOI : 10.5483/BMBRep.2014.47.8.106
Cell therapies utilizing mesenchymal stem cells (MSCs) have a great potential in many research and clinical settings. The mechanisms underlying the therapeutic effects of MSCs have been studied previously and the paracrine effects elicited by their production of various growth factors and cytokines were recognized as being crucial. However, the molecular controls that govern these paracrine effects remain poorly understood. To elucidate the molecular regulators of this process, we performed a global knockdown of microRNAs (miRNAs) in human adipose-derived mesenchymal stem cells (hADSCs) by inhibiting DGCR8, a key protein in miRNA biogenesis. Global disruption of miRNA biogenesis in hADSCs caused dramatic changes in the expression of subsets of growth factors and cytokines. By performing an extensive bioinformatic analysis, we were able to associate numerous putative miRNAs with these genes. Taken together, our results strongly suggest that miRNAs are essential for the production of growth factors and cytokines in hADSCs.