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BMB Reports

Mihyang Do, In-Hae Kwak, Ju-Hyun Ahn, In Jeong Lee, Jae-Ho Lee
Tetraploidy, a potential precursor of cancer-associated aneuploidy, is produced either by cell fusion or cytokinesis failure. Here, we used low p53-expressing HeLa cells to address the fate of cancer cells after fusion. We found that massive cell death or growth arrest occurred a few days after fusion. Interestingly, cells with larger nuclei preferentially died after fusion, suggesting that a larger deviation of DNA content is a strong inducer of apoptosis. Notably, a fraction of cells escaped cell death. It turned out that the stability of survivin was increased, and its localization changed preferentially to the cytosol in fused cells...
February 14, 2017: BMB Reports
Hyo Jin Maeng, Jae-Hwi Song, Goon-Tae Kim, Yoo-Jeong Song, Kangpa Lee, Jae-Young Kim, Tae-Sik Park
Ceramides are the major sphingolipid metabolites involved in cell survival and apoptosis. When HepG2 hepatoma cells were treated with celecoxib, the expression of the genes in de novo sphingolipid biosynthesis and sphingomyelinase pathway was upregulated and cellular ceramide was elevated. In addition, celecoxib induced endoplasmic reticulum (ER) stress in a time-dependent manner. SPTLC2, a subunit of serine palmitoyltransferase, was overexpressed by adenovirus. Adenoviral overexression of SPTLC2 (AdSPTLC2) decreased cell viability of HEK293 and HepG2 cells...
February 10, 2017: BMB Reports
Hsin-Sung Yeh, Wei Zhang, Jeongsik Yong
Alternations in usage of polyadenylation sites during transcription termination yield transcript isoforms from a gene. Recent findings of transcriptome-wide alternative polyadenylation (APA) as a molecular response to changes in biology position APA not only as a molecular event of early transcriptional termination but also as a cellular regulatory step affecting various biological pathways. With the development of high-throughput profiling technologies at a single nucleotide level and their applications targeted to the 3'-end of mRNAs, dynamics in the landscape of mRNA 3'-end is measureable at a global scale...
February 2, 2017: BMB Reports
Heejin Lee, Hyosun Tak, So Jung Park, Yoon Kyung Jo, Dong Hyung Cho, Eun Kyung Lee
Mitochondria play pivotal roles in the ATP production, apoptosis and generation of reactive oxygen species. Although dynamic regulation of mitochondria morphology is a critical step to maintain cellular homeostasis, the regulatory mechanisms are not yet fully elucidated. In this study, we identified miR-200a-3p as a novel regulator of mitochondrial dynamics by targeting mitochondrial fission factor (MFF). We demonstrated that the ectopic expression of miR-200a-3p enhanced mitochondrial elongation, increased mitochondrial ATP synthesis, mitochondrial membrane potential and oxygen consumption rate...
February 2, 2017: BMB Reports
Fabrice Lejeune
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism ensuring the fast decay of mRNAs harboring a premature termination codon (PTC). As a quality control mechanism, NMD distinguishes PTCs from normal termination codons in order to degrade PTC-carrying mRNAs only. For this, NMD is connected to various other cell processes which regulate or activate it under specific cell conditions or in response to mutations, mis-regulations, stresses, or particular cell programs. These cell processes and their connections with NMD are the focus of this review, which aims both to illustrate the complexity of the NMD mechanism and its regulation and to highlight the cellular consequences of NMD inhibition...
January 24, 2017: BMB Reports
Kyoung Mi Kim, Ji Heon Noh, Kotb Abdelmohsen, Myriam Gorospe
Mitochondria are cytosolic organelles essential for generating energy and maintaining cell homeostasis. Despite their critical function, the handful of proteins expressed by the mitochondrial genome is insufficient to maintain mitochondrial structure or activity. Accordingly, mitochondrial metabolism is fully dependent on factors encoded by the nuclear DNA, including many proteins synthesized in the cytosol and imported into mitochondria via established mechanisms. However, there is growing evidence that mammalian mitochondria can also import cytosolic noncoding RNA via poorly understood processes...
January 24, 2017: BMB Reports
Yu Jin Jang, Su Yeon An, Jong-Hoon Kim
Beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repairs promise potential therapeutic strategies against different diseases. However, key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action are not well defined. We found that the cell-free secretome of umbilical cord-derived MSCs had significant anti-fibrotic activity in mouse models of liver fibrosis. Our study demonstrated that the reduction in fibrosis was achieved by perturbing hepatic stellate cell activation by directly inhibiting TGFβ/Smad-signaling...
January 24, 2017: BMB Reports
Soo Jin Kim, Ho Min Kim
Toll-like receptor 4 (TLR4) together with MD2, one of the key pattern recognition receptors for a pathogen-associated molecular pattern, activates innate immunity by recognizing lipopolysaccharide (LPS) of Gram-negative bacteria. Although LBP and CD14 catalyze LPS transfer to the TLR4-MD2 complex, the detail mechanisms underlying this dynamic LPS transfer remain elusive. Using negative-stain electron microscopy, we visualized the dynamic intermediate complexes during LPS transfer-LBP/LPS micelles and ternary CD14/LBP/LPS micelle complexes...
January 24, 2017: BMB Reports
Incheol Ryu, Yoon Ki Kim
In mammals, cap-dependent translation of mRNAs is initiated by two distinct mechanisms: CBC-dependent translation (CT) and eIF4E-dependent translation (ET). Both translation initiation mechanisms share common features in driving cap-dependent translation; nevertheless, they can be distinguished from each other based on their molecular features and biological roles. CT is largely associated with mRNA surveillance, whereas ET is predominantly involved in the bulk of protein synthesis. However, several recent studies have demonstrated that CT and ET have similar roles in translational regulation...
January 16, 2017: BMB Reports
Sun-Uk Bak, Suji Kim, Hae-Jun Hwang, Yun Jung-A, Wan-Sung Kim, Moo-Ho Won, Ji-Yoon Kim, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron. It prevents the pathogenesis of several human diseases. Here we assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKL-induced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKL-induced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages...
January 16, 2017: BMB Reports
Hye-Jin Jung, Seung-Soon Im, Dae-Kyu Song, Jae-Hoon Bae
Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein (ox-LDL) and is implicated in its atherogenic activity. This study investigated the effects of LPC on cell viability, intracellular calcium homeostasis, and the protective mechanisms of chlorogenic acid (CGA) in human umbilical vein endothelial cells (HUVECs). LPC increased intracellular calcium ([Ca2+]i) by releasing Ca2+ from intracellular stores and via Ca2+ influx through store-operated channels (SOCs). LPC also increased the generation of reactive oxygen species (ROS) and decreased cell viability...
January 16, 2017: BMB Reports
Soonok Kim, Yun Sung Cho, Jong Bhak, Stephen J O'Brian, Joo-Hong Yeo
Recent advances in genome sequencing technologies enabled humans produce and investigate wild species genomes. This included a very large family of cats such as tiger, lion, and leopard. We have performed an in-depth comparative analysis to identify the genomic signatures in the evolution of felid to become the top carnivore predators on land. Our focus was on how carnivore genomes, compared to omnivore or herbivore, shared evolutionary adaptations in genes associated with nutrient metabolism, muscle strength, agility, and other traits responsible for hunting and meat digestion...
January 2, 2017: BMB Reports
Heegwon Shin, Jungmin Lee, Youngmi Kim, Seonghui Jang, Takbum Ohn, Younghoon Lee
Brain cytoplasmic 200 RNA (BC200 RNA) is a neuron-specific non-coding RNA that has been implicated in the inhibition of local synaptodendritic protein synthesis. It is also highly expressed in some cancer cells. Although BC200 RNA has been shown to inhibit translation in vitro, the cellular location of this inhibition was previously unknown. In this study, we used a BC200 RNA-recognizing antibody to identify the cellular locations of BC200 RNA in HeLa cervical carcinoma cells. We observed punctate signals in both the cytoplasm and nucleus, and further found that BC200 RNA colocalized with the p-body decapping enzyme, DCP1A, and heterogeneous nuclear ribonucleoprotein E2 (hnRNP E2)...
January 2, 2017: BMB Reports
Haemin Kim, Yong Deok Lee, Min Kyung Kim, Jun-Oh Kwon, Min-Kyoung Song, Zang Hee Lee, Hong-Hee Kim
Patients with inflammatory bone disease or cancer have an increased risk of fractures and delayed healing of bones. S100A4 protein is a member of the calcium-binding S100 protein family, which is abundantly expressed in inflammatory diseases and cancers. In this study, we investigated the effects of extracellular S100A4 on osteoblasts, cells responsible for bone formation. Treatment of mouse primary calvarial osteoblasts with recombinant S100A4 resulted in reductions in matrix mineralization. The expression of osteoblast marker genes including osteocalcin and osterix was also suppressed...
December 21, 2016: BMB Reports
Kiyoung Eun, Seok-Won Ham, Hyunggee Kim
Most of cancers still remain to be incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most issued therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, recurrence, and even acquired resistance after the anti-CSC therapies developed in experimental models...
December 20, 2016: BMB Reports
Kyungseop Ahn
Natural product drugs, or botanical drugs, are drugs composed of natural substances which has constituent and efficacy. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards on approving drug sales varies by countries...
December 20, 2016: BMB Reports
Min Hee Park, Namoh Kim, Hee Kyung Jin, Hee Kyung Bae
Ovariectomy-induced bone loss is related to an increased deposition of osteoclasts on bone surfaces. We reported that the 36-amino-acid-long neuropeptide Y (NPY) could mobilize hematopoietic stem/progenitor cells (HSPCs) from the bone marrow to the peripheral blood by regulating HSPC maintenance factors and that mobilization of HSPCs ameliorated low bone density in an ovariectomy-induced osteoporosis mouse model by reducing the number of osteoclasts. Here, we demonstrated that new NPY peptides, recombined from the cleavage of the full-length NPY, showed better functionality for HSPC mobilization than the full-length peptide...
December 20, 2016: BMB Reports
Da Hyun Lee, Jeong Su Park, Yu Seol Lee, Su Haeng Sung, Yong-Ho Lee, Soo Han Bae
Nuclear factor erythroid 2-related factor 2 (Nrf2) provides cellular defense against oxidative stress by inducing the expression of antioxidant and detoxification enzymes. The calcium antagonist verapamil is an FDA-approved drug prescribed for the treatment of hypertension. Here, we show that verapamil acts as a potent Nrf2 activator without causing cytotoxicity through degradation of Kelch-like ECH-associated protein 1 (Keap1), an Nrf2 repressor. Furthermore, verapamil-induced Keap1 degradation is prominently mediated by a p62-dependent autophagic pathway...
December 20, 2016: BMB Reports
Mi Hye Song, Varun Sasidharan Nair, Kwon Ik Oh
Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in CD4+Foxp3+ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes...
December 9, 2016: BMB Reports
Sunhwa Oh, Hyungjoo Kim, KeeSoo Nam, Incheol Shin
Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/MAPK signaling pathway and integrin β1/Src/FAK signaling pathways...
December 9, 2016: BMB Reports
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