Resveratrol enhances cisplatin-induced apoptosis in human hepatoma cells via glutamine metabolism inhibition.
Abstract Cisplatin is one of the most effective chemotherapeutic drugs used in the treatment of HCC, but many patients will ultimately relapse with cisplatin-resistant disease. Used in combination with cisplatin, resveratrol has synergistic effect of increasing chemosensitivity of cisplatin in various cancer cells. However, the mechanisms of resveratrol enhancing cisplatin-induced toxicity have not been well characterized. Our study showed that resveratrol enhances cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism. Further studies reveal that resveratrol decreases the absorption of gl...
Source: BMB Reports - August 14, 2018 Category: Biochemistry Authors: Liu Z, Peng Q, Li Y, Gao Y Tags: BMB Rep Source Type: research

The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis.
Abstract Purinergic receptor signaling is increasingly recognized as an important regulator of inflammation. The P2X family purinergic receptors P2X5 and P2X7 have both been implicated in bone biology, and it has been suggested recently that P2X5 may be a significant regulator of inflammatory bone loss. However, a role for P2X5 in periodontitis is unknown. The present study aimed to evaluate the functional role of P2X5 in ligature-induced periodontitis in mice. Five days after placement of ligature, analysis of alveolar bone revealed decreased bone loss in P2rx5-/- mice compared to P2rx7-/- and WT control mice. Ge...
Source: BMB Reports - August 14, 2018 Category: Biochemistry Authors: Kim H, Kajikawa T, Walsh MC, Takegahara N, Jeong YH, Hajishengallis G, Choi Y Tags: BMB Rep Source Type: research

Oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into stress granules.
Abstract The Alu element, the most abundant transposable element, is transcribed to Alu RNA. We hypothesized that the PIWI protein regulates the expression of Alu RNA in retinal pigment epithelial (RPE) cells, where accumulated Alu RNA leads to macular degeneration. Alu transcription was induced in RPE cells treated with H2O2. At an early stage of oxidative stress, PIWIL4 was translocated into the nucleus; however, subsequently it was sequestered into cytoplasmic stress granules, resulting in the accumulation of Alu RNA. An elevated amount of Alu RNA was positively correlated with the disruption of the epithelial ...
Source: BMB Reports - August 14, 2018 Category: Biochemistry Authors: Hwang YE, Baek Y, Baek A, Kim DE Tags: BMB Rep Source Type: research

Defect of SIRT1-FoxO3a axis is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated cellular senescence and nematode aging.
Abstract We investigated whether SIRT1 is associated with reactive oxygen species (ROS) accumulation during CK2 downregulation-mediated senescence. SIRT1 overexpression suppressed ROS accumulation, reduced transcription of FoxO3a target genes, and nuclear export and acetylation of FoxO3a, which were induced by CK2 downregulation in HCT116 and MCF-7 cells. Conversely, overexpression of a dominant-negative mutant SIRT1 (H363Y) counteracted decreased ROS levels, increased transcriptional activity of FoxO3a, and increased nuclear import and decreased acetylation of FoxO3a, which were induced by CK2 upregulation. CK2 d...
Source: BMB Reports - August 14, 2018 Category: Biochemistry Authors: Ham HJ, Park JW, Bae YS Tags: BMB Rep Source Type: research

The Road less Traveled: Strategies to Enhance the Frequency of Homology-Directed Repair (HDR) for Increased Efficiency of CRISPR/Cas-Mediated Transgenesis.
Abstract Non-homologous end joining (NHEJ), and to a lesser extent, the error-free pathway known as homology-directed repair (HDR) are cellular mechanisms for recovery from double-strand DNA breaks (DSB) induced by RNA-guided programmable nuclease CRISPR/Cas. Since NHEJ is equivalent to using a duck tape to stick two pieces of metals together, the outcome of this repair mechanism is prone to error. Any out-of-frame mutations or premature stop codons resulting from NHEJ repair mechanism are extremely handy for loss-of-function studies. Substitution of a mutation on the genome with the correct exogenous repair DNA r...
Source: BMB Reports - August 14, 2018 Category: Biochemistry Authors: Devkota S Tags: BMB Rep Source Type: research

OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.
Abstract Upon viral infection, the 2', 5'-oligoadenylate synthetase (OAS)-ribonuclease L (RNaseL) system works to cleave viral RNA, thereby blocking viral replication. However, it is unclear whether OAS proteins have a role in regulating gene expression. Here, we show that OAS1 and OAS3 act as negative regulators of the expression of chemokines and interferon-responsive genes in human macrophages. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) technology was used to engineer human myeloid cell lines in which the OAS1 or OAS3 gene was deleted. Neither ...
Source: BMB Reports - August 6, 2018 Category: Biochemistry Authors: Lee WB, Choi WY, Lee DH, Shim H, Kim-Ha J, Kim YJ Tags: BMB Rep Source Type: research

Strengthened connections between engrams encode specific memories.
Abstract In previous studies, memory storage was localized to engram cells distributed across the brain. While these studies have provided an individual cellular profile of engram cells, their synaptic connectivity, or whether they follow Hebbian mechanisms, remains uncertain. Therefore, our recent study investigated whether synapses between engram cells exhibit selectively enhanced structural and functional properties following memory formation. This was accomplished using a newly developed technique called "dual-eGRASP". We found that the number and size of spines on CA1 engram cells that receive input...
Source: BMB Reports - August 6, 2018 Category: Biochemistry Authors: Kim JI, Choi DI, Kaang BK Tags: BMB Rep Source Type: research

Dishevelling Wnt and Hippo.
Abstract As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to β-catenin in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains u...
Source: BMB Reports - August 6, 2018 Category: Biochemistry Authors: Kim NH, Lee Y, Yook JI Tags: BMB Rep Source Type: research

Potential involvement of Drosophila flightless-1 in carbohydrate metabolism.
Abstract Our previous study indicates that Drosophila Flightless-1 controls lipid metabolism, and that there is accumulation of triglycerides in flightless-1 (fliI)-mutant flies, where this mutation triggers metabolic stress and an obesity phenotype. Here, with the aim to characterize the function of FliI in metabolism, we analyzed the gene expression and levels of metabolites in fliI-mutant flies. The levels of enzymes related to glycolysis, lipogenesis, and the pentose phosphate pathway increased in fliI mutants; this result is consistent with the levels of metabolites corresponding to a metabolic pathway. Moreo...
Source: BMB Reports - July 31, 2018 Category: Biochemistry Authors: Park JE, Jang J, Lee EJ, Kim SJ, Yoo HJ, Lee S, Kang MJ Tags: BMB Rep Source Type: research

The protective effects of ethanolic extract of Clematis terniflora against corticosterone-induced neuronal damage via the AKT and ERK1/2 pathway.
In this study, we evaluated the neuroprotective effects of Clematis terniflora extract (CTE) against corticosterone-induced apoptosis in rat pheochromocytoma (PC12) cells, and also investigated the underlying molecular mechanisms. At concentrations of 300 and 500 µg/mL, CTE significantly decreased apoptotic cell death and mitochondrial damage induced by 200 µM corticosterone. CTE decreased the expression levels of endoplasmic reticulum (ER) stress proteins GRP78, GADD153, and mitochondrial damage-related protein BAD, suggesting that it downregulates ER stress evoked by corticosterone. Furthermore, our results s...
Source: BMB Reports - July 24, 2018 Category: Biochemistry Authors: Noh Y, Cheon S, Kim IH, Kim I, Lee SA, Kim DH, Jeong Y Tags: BMB Rep Source Type: research

MiR-363 Inhibits Cisplatin Chemoresistance of Epithelial Ovarian Cancer by Regulating Snail-Induced Epithelial-Mesenchymal Transition.
In this study, it was indicated that miR-363 downregulation was significantly correlated with EOC carcinogenesis and cisplatin resistance. Moreover, miR-363 overexpression could resensitise cisplatin-resistant EOC cells to cisplatin treatment both in vitro and in vivo. In addition, data revealed that EMT inducer Snail was significantly upregulated in cisplatin-resistant EOC cell lines and EOC patients and was a functional target of miR-363 in EOC cells. Furthermore, snail overexpression could significantly attenuate miR-363-suppressed cisplatin resistance of EOC cells, suggesting that miR-363-regulated cisplatin resistance...
Source: BMB Reports - July 24, 2018 Category: Biochemistry Authors: Cao L, Wan Q, Li F, Tang CE Tags: BMB Rep Source Type: research

Thalamo-cortical System Involving Higher-order Nuclei in Patients with First-Episode Psychosis.
Abstract Based on the piling reports of disruptions in the thalamus of patients with schizophrenia, the alteration in the thalamo-cortical system has been regarded as the core pathophysiology. As the thalamus is composed of distinctive nuclei with different cytoarchitecture and cortical connections, nuclei specific investigations have been actively conducted in post-mortem studies. In addition, the importance of early changes has been highlighted, which in turn has led to investigations of the thalamo-cortical system using non-invasive neuroimaging methods. From this perspective, the early structural changes in th...
Source: BMB Reports - July 24, 2018 Category: Biochemistry Authors: Cho KIK, Kwak YB, Hwang WJ, Lee J, Kim M, Lee TY, Kwon JS Tags: BMB Rep Source Type: research

Dyslipidemia promotes germinal center reactions via IL-27.
Abstract Cardiovascular disease such as atherosclerosis is caused by imbalanced lipid metabolism and represents a leading cause of death worldwide. Epidemiological studies show that patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate the incidence of autoimmune diseases in humans and in animal models. However, there is a considerable gap in our understanding of how atherosclerosis impacts the development of the autoimmunity in humans, and vice versa. The atherosclerosis-related autoimmune diseases include psoriasis, rheum...
Source: BMB Reports - July 24, 2018 Category: Biochemistry Authors: Ryu H, Chung Y Tags: BMB Rep Source Type: research

Investigating the role of Sirtuins in cell reprogramming.
Abstract Cell reprogramming has been considered a powerful technique in the regenerative medicine field. In addition to diverse its strengths, cell reprogramming technology also has several drawbacks generated during the process of reprogramming. Telomere shortening caused by the cell reprogramming process impedes the efficiency of cell reprogramming. Transcription factors used for reprogramming alter genomic contents and result in genetic mutations. Additionally, defective mitochondria functioning such as excessive mitochondrial fission leads to the limitation of pluripotency and ultimately reduces the efficiency...
Source: BMB Reports - July 24, 2018 Category: Biochemistry Authors: Shin J, Kim J, Park H, Kim J Tags: BMB Rep Source Type: research

An engineered PD-1-based and MMP-2/9-oriented fusion protein exerts potent antitumor effects against melanoma.
This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy. PMID: 30021673 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - July 19, 2018 Category: Biochemistry Authors: Wei M, Liu X, Cao C, Yang J, Lv Y, Huang J, Wang Y, Qin Y Tags: BMB Rep Source Type: research

Activation of formyl peptide receptor 2 by WKYMVm enhances emergency granulopoiesis through phospholipase C activity.
Abstract Emergency granulopoiesis is a very important strategy to supply efficient neutrophil number in response to infection. However, molecular mechanism involved in this process remains unclear. Here, we found that administration of WKYMVm, an immune modulating peptide, to septic mice strongly increased neutrophil number through augmented emergency granulopoiesis. WKYMVm-induced emergency granulopoiesis was blocked not only by a formyl peptide receptor 2 (FPR2) antagonist (WRW4), but also by FPR2 deficiency. As progenitors of neutrophils, Lin-c-kit+Sca-1- cells expressed FPR2. WKYMVm-induced emergency granulopo...
Source: BMB Reports - July 19, 2018 Category: Biochemistry Authors: Kim HS, Park MY, Lee SK, Park JS, Lee HY, Bae YS Tags: BMB Rep Source Type: research

Inactivation of Sirtuin2 protects mice from acetaminophen-induced liver injury: possible involvement of ER stress and S6K1 activation.
This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries. PMID: 30021675 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - July 19, 2018 Category: Biochemistry Authors: Lee DH, Lee B, Park JS, Lee YS, Kim JH, Cho Y, Jo Y, Kim HS, Lee YH, Nam KT, Bae SH Tags: BMB Rep Source Type: research

Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation.
Abstract Homotypic cell-in-cell (CIC) structures forming between cancer cells were proposed to promote tumor evolution via entosis, a nonapoptotic cell death process. However, the mechanisms underlying their formation remained poorly understood. We performed a microarray analysis to identify genes associated with homotypic CIC formation. Cancer cells differing in their ability to form homotypic CIC structures were selected for the study. Association analysis identified 73 probe sets for 62 candidate genes potentially involved in CIC formation. Among them, twenty-one genes were downregulated while 41 genes were upr...
Source: BMB Reports - July 19, 2018 Category: Biochemistry Authors: Ruan B, Wang C, Chen A, Liang J, Niu Z, Zheng Y, Fan J, Gao L, Huang H, Wang X, Sun Q Tags: BMB Rep Source Type: research

Exosomes Derived from MicroRNA-584 Transfected Mesenchymal Stem Cells: Novel Alternative Therapeutic Vehicles for Cancer Therapy.
Abstract Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associa...
Source: BMB Reports - July 3, 2018 Category: Biochemistry Authors: Kim R, Lee S, Lee J, Kim M, Kim WJ, Lee HW, Lee MY, Kim J, Chang W Tags: BMB Rep Source Type: research

3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates MPP+-induced cytotoxicity by regulating oxidative stress and mitochondrial dysfunction in SH-SY5Y cells.
Abstract Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against MPP+-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 sign...
Source: BMB Reports - July 3, 2018 Category: Biochemistry Authors: Yang SJ, Yang JW, Na JM, Ha JS, Choi SY, Cho SW Tags: BMB Rep Source Type: research

Cellular coordination controlling organ separation and surface integrity in plants.
Abstract Plants are unable to relocate themselves to a more favorable location and thus have to deal with developmental programs and environmental cues wherever they happen to be. It is yet largely unknown as to how plant cells coordinate cellular activities and architectures to accomplish developmental processes and responses to environmental change. By identifying and establishing a new cellular model system, we have recently uncovered that two neighboring cell types in abscission zone (AZ) of Arabidopsis flowers coordinate physiological states and elaborate differential cellular architectures to precisely separ...
Source: BMB Reports - July 3, 2018 Category: Biochemistry Authors: Lee Y, Kwak JM Tags: BMB Rep Source Type: research

TRRAP Stimulates the Tumorigenic Potential of Ovarian Cancer Stem Cells.
Abstract Ovarian cancer is the most fatal gynecological malignancy in women and identification of new therapeutic targets is essential for the continued development of therapy for ovarian cancer. TRRAP (transformation/transcription domain-associated protein) is an adaptor protein and a component of histone acetyltransferase complex. The present study was undertaken to investigate the roles played by TRRAP in the proliferation and tumorigenicity of ovarian cancer stem cells. TRRAP expression was found to be up-regulated in the sphere cultures of A2780 ovarian cancer cells. Knockdown of TRRAP significantly decreased...
Source: BMB Reports - June 25, 2018 Category: Biochemistry Authors: Kang KT, Kwon YW, Kim DK, Lee SI, Kim KH, Suh DS, Kim JH Tags: BMB Rep Source Type: research

Genomic characterization of clonal evolution during oropharyngeal carcinogenesis driven by human papillomavirus 16.
Abstract Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of...
Source: BMB Reports - June 25, 2018 Category: Biochemistry Authors: Chae J, Park WS, Kim MJ, Jang SS, Hong D, Ryu J, Ryu CH, Kim JH, Choi MK, Cho KH, Moon SH, Yun T, Kim JI, Jung YS Tags: BMB Rep Source Type: research

LJ-1888, a selective antagonist for the A3 adenosine receptor, ameliorates the development of atherosclerosis and hypercholesterolemia in apolipoprotein E knock-out mice.
This study assessed whether LJ-1888, a selective antagonist for A3 AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out (ApoE-/-) mice who are fed a western diet. Plaque formation was significantly lower in ApoE-/- mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of ApoE-/- mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in ApoE-/- mice administ...
Source: BMB Reports - June 25, 2018 Category: Biochemistry Authors: Park JG, Jeong SJ, Yu J, Kim G, Jeong LS, Oh GT Tags: BMB Rep Source Type: research

Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in a mice model.
In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic β-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of NF-κB and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects...
Source: BMB Reports - June 25, 2018 Category: Biochemistry Authors: Yeo HJ, Yeo EJ, Shin MJ, Choi YJ, Lee CH, Kwon HY, Kim DW, Eum WS, Choi SY Tags: BMB Rep Source Type: research

Telomere association of Oryza sativa Telomere Repeat-binding Factor Like 1 and its roles in telomere maintenance and development in rice, Oryza sativa L.
In this study, we identified and characterized OsTRFL1 (Oryza sativa Telomere Repeat-binding Factor Like 1) in rice, a monocot model crop. Although OsTRFL1 did not directly bind to telomere repeats (TTTAGGG)4 in vitro, it was associated with telomeric sequences in planta. OsTRFL1 interacted with rice TBPs, such as OsTRBF1 and RTBP1, in yeast and plant cells as well as in vitro. Thus, it seems likely that the association of OsTRFL1 with other TBPs enables OsTRFL1 to bind to telomeres indirectly. T-DNA inserted OsTRFL1 knock-out mutant rice plants displayed significantly longer telomeres (6-25 kb) than those (5-12 kb) in wil...
Source: BMB Reports - June 25, 2018 Category: Biochemistry Authors: Byun MY, Cui LH, Lee H, Kim WT Tags: BMB Rep Source Type: research

Potential roles of reactive oxygen species derived from chemical substances involved in cancer development in the female reproductive system.
Abstract Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately, by reprogramming cancer cell metabolism. This review provides up to date findings regarding the role of ROS generation induced by diverse biological molecules and chemicals in representative women's' cancer. Specifically, we describe ...
Source: BMB Reports - June 20, 2018 Category: Biochemistry Authors: Kim SM, Hwang KA, Choi KC Tags: BMB Rep Source Type: research

Superoxide dismutase 3 protects mesenchymal stem cells through enhanced autophagy and regulation of FoxO3a trafficking.
In this study, we overexpressed SOD3 in MSCs (SOD3-MSCs) and evaluated its effect under serum starvation conditions. Nutritional limitation can decrease the survival rate of transplanted MSCs and thus can reduce their efficacy during therapy. Interestingly, we found that SOD3-MSCs exhibited reduced reactive oxygen species levels and greater survival rates than normal MSCs under serum-deprived conditions. In addition, overexpression of SOD3 attenuated starvation-induced apoptosis with increased autophagy in MSCs. Moreover, we have demonstrated that SOD3 protects MSCs against the negative effects of serum deprivation via mod...
Source: BMB Reports - June 20, 2018 Category: Biochemistry Authors: Agrahari G, Sah SK, Kim TY Tags: BMB Rep Source Type: research

Actin-binding LIM Protein 1 Regulates Receptor Activator of NF- κB Ligand-Mediated Osteoclast Differentiation and Motility.
Actin-binding LIM Protein 1 Regulates Receptor Activator of NF-κB Ligand-Mediated Osteoclast Differentiation and Motility. BMB Rep. 2018 Jun 20;: Authors: Jin SH, Kim H, Gu DR, Park KH, Lee YR, Choi Y, Lee SH Abstract Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. ABLIM...
Source: BMB Reports - June 20, 2018 Category: Biochemistry Authors: Jin SH, Kim H, Gu DR, Park KH, Lee YR, Choi Y, Lee SH Tags: BMB Rep Source Type: research

Application of genome engineering for treatment of retinal diseases.
Abstract Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) system can be sued as a tool to correct pathological mutations or modulate gene expression levels associated with pathogenesis of human diseases. Owing to well-established local administration methods including intravitreal and subretinal injection, it is relatively easy to administer therapeutic genome engineering machinery to ocular tissues for treating retinal diseases. In this context, we have investigated the potential of in vivo genome engineering as a therapeutic approach in the form of ribonucleoprotein or C...
Source: BMB Reports - June 20, 2018 Category: Biochemistry Authors: Jo DH, Kim JH Tags: BMB Rep Source Type: research

The multifunctional RNA-binding protein hnRNPK is critical for the proliferation and differentiation of myoblasts.
Abstract HnRNPK is a multifunctional protein that participates in chromatin remodeling, transcrip-tion, RNA splicing, mRNA stability and translation. Here, we uncovered the function of hnRNPK in regulating the proliferation and differentiation of myoblasts. hnRNPK was mutated in the C2C12 myoblast cell line using the CRISPR/Cas9 system. A decreased proliferation rate was observed in hnRNPK-mutated cells, suggesting an impaired prolif-eration phenotype. Furthermore, increased G2/M phase, decreased S phase and increased sub-G1 phase cells were detected in the hnRNPK-mutated cell lines. The expression analysis of key...
Source: BMB Reports - June 14, 2018 Category: Biochemistry Authors: Xu Y, Li R, Zhang K, Wu W, Wang S, Zhang P, Xu H Tags: BMB Rep Source Type: research

Facile Analysis of Protein-Protein Interactions in Living Cells by Enriched Visualization of the P-body.
Abstract Protein-Protein Interactions (PPIs) play essential roles in diverse biological processes and their misregulations are associated with a wide range of diseases. Especially, the growing attention to PPIs as a new class of therapeutic target is increasing the need for an efficient method of cell-based PPI analysis. Thus, we newly developed a robust PPI assay (SeePPI) based on the co-translocation of interacting proteins to the discrete subcellular compartment 'processing body' (p-body) inside living cells, enabling a facile analysis of PPI by the enriched fluorescent signal. The feasibility and strength of S...
Source: BMB Reports - June 14, 2018 Category: Biochemistry Authors: Choi M, Baek J, Han SB, Cho S Tags: BMB Rep Source Type: research

BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer.
Abstract Triple-negative breast cancer (TNBC) is considered to be a notorious type of cancer due to its aggressive metastatic potential and poor prognosis. Recent evidence suggests that BLT2, a low-affinity LTB4 receptor is critically associated with the phenotypes of TNBC cells, including invasion, metastasis, and survival. Furthermore, in a group of 545 breast cancer patients with metastasis, we observed that the high-BLT2 subgroup had a lower disease-free-survival rate than the low-BLT2 subgroup. Thus, we theorized that anti-BLT2 strategies could facilitate the development of new therapies used for TNBC. This r...
Source: BMB Reports - June 14, 2018 Category: Biochemistry Authors: Park J, Jang JH, Park GS, Chung Y, You HJ, Kim JH Tags: BMB Rep Source Type: research

With the greatest care, stromal interaction molecule (STIM) proteins verify what skeletal muscle is doing.
Abstract Skeletal muscle contracts or relaxes to maintain the body position and locomotion. For the contraction and relaxation of skeletal muscle, Ca2+ in the cytosol of skeletal muscle fibers acts as a switch to turn on and off a series of contractile proteins. The cytosolic Ca2+ level in skeletal muscle fibers is governed mainly by movement of Ca2+ between the cytosol and the sarcoplasmic reticulum (SR). Store-operated Ca2+ entry (SOCE), a Ca2+ entryway from the extracellular space to the cytosol, has gained a significant amount of attention from muscle physiologists. Orai1 and stromal interaction molecule 1 (ST...
Source: BMB Reports - June 14, 2018 Category: Biochemistry Authors: Cho CH, Lee KJ, Lee EH Tags: BMB Rep Source Type: research

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.
Abstract Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico da...
Source: BMB Reports - May 28, 2018 Category: Biochemistry Authors: Yang S, Lee JY, Hur H, Oh JH, Kim MH Tags: BMB Rep Source Type: research

29-kDa FN-f inhibited autophagy through modulating localization of HMGB1 in human articular chondrocytes.
In this study, we investigated whether changes induced by 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1-modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in ...
Source: BMB Reports - May 28, 2018 Category: Biochemistry Authors: Hwang HS, Choi MH, Kim HA Tags: BMB Rep Source Type: research

Anti-inflammatory effects of a novel compound, MPQP, through the inhibition of IRAK1 signaling pathways in LPS-stimulated RAW 264.7 macrophages.
In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of...
Source: BMB Reports - May 28, 2018 Category: Biochemistry Authors: Kim BR, Cho YC, Cho S Tags: BMB Rep Source Type: research

MiR-204 acts as a potential therapeutic target in acute myeloid leukemia by increasing BIRC6-mediated apoptosis.
Abstract Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significa...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Wang Z, Luo H, Fang Z, Fan Y, Liu X, Zhang Y, Rui S, Chen Y, Hong L, Gao J, Zhang M Tags: BMB Rep Source Type: research

Osteoclast-derived SLIT3 is a coupling factor linking bone resorption to bone formation.
Abstract We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation of β-catenin. Autocrine signaling by SLIT3 also inhibited bone resorption by suppressing the fusion and differentiation of pre-osteoclasts. All mice lacking Slit3 or its receptor Robo1 showed an osteopenic phenotype with low bone formation and high bone resorption. A small truncated recombinant SLIT3 protein increased bone mass in an osteopenic mouse ...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Koh JM Tags: BMB Rep Source Type: research

Deubiquitinase USP35 as a novel mitotic regulator via maintenance of Aurora B stability.
Abstract Aurora B is an important kinase involved in dynamic cellular events in mitosis. Aurora B activity is controlled by several post-translational modifications (PTMs). Among them, E3 ubiquitin ligase-mediated ubiquitination plays crucial roles in controlling the relocation and degradation of Aurora B. Aurora B, ubiquitinated by different E3 ligases, moves to the exact site for its mitotic function during metaphase-anaphase transition and is then degraded for cell cycle progression at the end of mitosis. However, how the stability of Aurora B is maintained until its degradation has been poorly understood. Rece...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Park J, Song EJ Tags: BMB Rep Source Type: research

Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans.
Abstract Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response (UPRmt), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Kwon S, Kim EJE, Lee SV Tags: BMB Rep Source Type: research

Cancer stem cell metabolism: target for cancer therapy.
Abstract Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies. Emerging evidence has shown that CSCs have a different metabolic phenotype to that of differen...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Chae YC, Kim JH Tags: BMB Rep Source Type: research

Laminopathies; Mutations on single gene and various human genetic diseases.
Abstract Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy. In this review...
Source: BMB Reports - May 16, 2018 Category: Biochemistry Authors: Kang SM, Yoon MH, Park BJ Tags: BMB Rep Source Type: research

Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes.
In this report, we explored the regulatory activity of hindsiipropane B on HIV-1 Tat-mediated chemokine production and its mode of action in astrocytes. Hindsiipropane B significantly alleviated HIV-1 Tat-mediated production of inflammatory chemokines, CCL2, CXCL8, and CXCL10. Hindsiipropane B inhibited expression of HDAC6, which is important regulator in HIV-1 Tat-mediated chemokine production. Hindsiipropane B diminished HIV-1 Tat-mediated reactive oxygen species (ROS) generation and NADPH oxidase activation/expression. Furthermore, hindsiipropane B inhibited HIV-1 Tat-mediated signaling cascades including MAPK, NF-&kapp...
Source: BMB Reports - April 27, 2018 Category: Biochemistry Authors: Jo H, Jang HY, Youn GS, Kim D, Lee CY, Jang JH, Choi SY, Jun JG, Park J Tags: BMB Rep Source Type: research

Chitinase 3-like-1, a novel regulator of Th1/CTL responses, as a therapeutic target for increasing anti-tumor immunity.
This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity. PMID: 29699605 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - April 27, 2018 Category: Biochemistry Authors: Kim DH, Choi JM Tags: BMB Rep Source Type: research

Insulin Receptor Substrate 2: A Bridge between Hippo and AKT Pathways.
Abstract NAFLD induces the development of advanced liver diseases such as NASH and liver cancer. Therefore, understanding the mechanism of NAFLD development is critical for its prevention and treatment. Ablation of PTEN or Hippo pathway components induces liver cancer in a murine model by hyperactive AKT or YAP/TAZ, respectively. Although the regulation of these two pathways occurs in the same hepatocyte, the details of crosstalk between Hippo-YAP/TAZ and PTEN-AKT pathways in liver homeostasis and tumorigenesis still remain unclear. Here, we found that depletion of both PTEN and SAV1 in liver promotes spontaneous ...
Source: BMB Reports - April 27, 2018 Category: Biochemistry Authors: Jeong SH, Lim DS Tags: BMB Rep Source Type: research

Degradation or aggregation: the ramifications of post-translational modifications on tau.
Abstract Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and contributes to the stability of microtubules in axons. Despite of its basic isoelectric point and high solubility, tau is often found in intraneuronal filamentous inclusions such as paired helical filaments (PHFs), which are the primary constituent of neurofibrillary tangles (NFTs). This pathological feature is the nosological entity termed "tauopathies" which notably include Alzheimer's disease (AD). A proteinaceous signature of all tauopathies is hyperphosphorylation of the accumulated tau, which has been extensiv...
Source: BMB Reports - April 17, 2018 Category: Biochemistry Authors: Park S, Lee JH, Lee MJ Tags: BMB Rep Source Type: research

Long noncoding RNA: multiple players in gene expression.
Abstract Previously considered as a component of transcriptional noise, long noncoding RNAs ( lncRNAs) were neglected as a therapeutic target, however, recently increasing evidence has shown that lncRNAs can participate in numerous biological processes involved in genetic regulation including epigenetic, transcriptional, and post-transcriptional regulation. In this review, we discuss the fundamental functions of lncRNAs at different regulatory levels and their roles in metabolic balance. Typical examples are introduced to illustrate their diverse molecular mechanisms. The comprehensive investigation and identifica...
Source: BMB Reports - April 11, 2018 Category: Biochemistry Authors: Chen X, Sun Y, Cai R, Wang G, Shu X, Pang W Tags: BMB Rep Source Type: research

Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production.
Abstract The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP (Basic Leucine Zipper)) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a fu...
Source: BMB Reports - April 11, 2018 Category: Biochemistry Authors: Lee SD, Yu KL, Park SH, Jung YM, You JC Tags: BMB Rep Source Type: research

The role of necroptosis in the treatment of diseases.
Abstract Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to cell stress. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore...
Source: BMB Reports - April 11, 2018 Category: Biochemistry Authors: Cho YS Tags: BMB Rep Source Type: research