UBE2S promotes the proliferation and survival of human lung adenocarcinoma cells.
In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Liu Z, Xu L Tags: BMB Rep Source Type: research

Disease model organism for Parkinson Disease: Drosophila melanogaster.
Abstract Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective and progressive loss of dopaminergic neurons. Genetic and environmental risk factors are associated with this disease. The genetic factors are composed of approximately 20 genes, such as SNCA, parkin, PTEN-induced kinase1 (pink1), leucine-rich repeat kinase 2 (LRRK2), ATP13A2, MAPT, VPS35, and DJ-1, whereas the environmental factors consist of oxidative stress-induced toxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), rotenone, and paraquat. The analyses of their functions and mechanisms have pro...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Aryal B, Lee Y Tags: BMB Rep Source Type: research

SPINK1 promotes cell growth and metastasis of lung adenocarcinoma and acts as a novel prognostic biomarker.
Abstract Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration, and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12). We observed that SPINK1 expression was only up-regulated in lung adenocarcinoma (LAC) tissues, and was an independent prognostic factor for poor survival. Our results indicate that SPINK1 might be a potential biomarker for LAC that promotes progre...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Xu L, Lu C, Huang Y, Zhou J, Wang X, Liu C, Chen J, Le H Tags: BMB Rep Source Type: research

SETDB1 regulates SMAD7 expression for breast cancer metastasis.
Abstract Breast cancer (BRC) is the most invasive cancer in women. Although the survival rate of BRC is gradually increasing due to improved screening systems, development of novel therapeutic targets for inhibition of BRC proliferation, metastasis and recurrence have been constantly needed. Thus, in this study, we identified overexpression of SETDB1 (SET Domain Bifurcated 1), a histone methyltransferase, in RNA-seq data of BRC derived from TCGA portal. In Gene Ontology (GO) analysis, cell migration-related GO terms were enriched, and we confirmed down-regulation of cell migration/invasion and alteration of EMT /M...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Ryu TY, Kim K, Kim SK, Oh JH, Min JK, Jung CR, Son MY, Kim DS, Cho HS Tags: BMB Rep Source Type: research

Tat-ATOX1 inhibits inflammatory responses via regulation of MAPK and NF- κB pathways.
Tat-ATOX1 inhibits inflammatory responses via regulation of MAPK and NF-κB pathways. BMB Rep. 2018 Dec 14;: Authors: Kim DW, Shin MJ, Choi YJ, Kwon HJ, Lee SH, Lee S, Park J, Han KH, Eum WS, Choi SY Abstract Antioxidant 1 (ATOX1) protein has been reported to exhibit various protective functions, including antioxidant and chaperone. However, the effects of ATOX1 on the inflammatory response has not been fully elucidated. Thus, we prepared cell permeable Tat-ATOX1 and studied the effects on lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13- acetate (TPA)-induced inflammation. Experimenta...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Kim DW, Shin MJ, Choi YJ, Kwon HJ, Lee SH, Lee S, Park J, Han KH, Eum WS, Choi SY Tags: BMB Rep Source Type: research

Growth Signaling and Longevity in Mouse Models.
Abstract Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene ho...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Kim SS, Lee CK Tags: BMB Rep Source Type: research

Mitochondria and aging.
Abstract Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanism of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately cause...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Son JM, Lee C Tags: BMB Rep Source Type: research

Modulation of senoinflammation by calorie restriction based on biochemical and Omics big data analysis.
Abstract Aging is a complex and progressive process characterized by physiological and functional decline with time that increases susceptibility to diseases. Aged-related functional change is accompanied by a low-grade, unresolved chronic inflammation as a major underlying mechanism. In order to explain aging in the context of chronic inflammation, a new integrative concept on age-related chronic inflammation is necessary that encompasses much broader and wider characteristics of cells, tissues, organs, systems, and interactions between immune and non-immune cells, metabolic and non-metabolic organs. We have prev...
Source: BMB Reports - December 14, 2018 Category: Biochemistry Authors: Bang E, Lee B, Noh SG, Kim DH, Jung HJ, Ha S, Yu BP, Chung HY Tags: BMB Rep Source Type: research

Juxtacrine regulation of cellular senescence.
Abstract Cellular senescence is defined as a state of stable cell cycle exit in response to various stimuli, which includes both cytotoxic stress and physiological cues. In addition to the core non-proliferative aspect, senescence is associated with diverse functionalities, which contribute to the role of senescence in a wide range of pathological and physiological processes. Such functionality is often mediated by the capability of senescent cells to communicate with their surroundings. Emerging evidence suggests that senescence is not a single entity, but a dynamic and heterogeneous collective phenotype. Underst...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Narita M Tags: BMB Rep Source Type: research

Sirtuin signaling in cellular senescence and aging.
This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide. PMID: 30526767 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Lee SH, Lee JH, Lee HY, Min KJ Tags: BMB Rep Source Type: research

Metabolic features and regulation in cell senescence.
Abstract Organismal aging is accompanied by a host of progressive metabolic alterations and an accumulation of senescent cells, along with functional decline and the appearance of multiple diseases. This implies that the metabolic features of cell senescence may contribute to the organism's metabolic changes and be closely linked to age-associated diseases, especially metabolic syndromes. However, there is no clear understanding of senescent metabolic characteristics. Here, we review key metabolic features and regulators of cellular senescence, focusing on mitochondrial dysfunction and anabolic deregulation, and t...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Kwon SM, Hong SM, Lee YK, Min S, Yoon G Tags: BMB Rep Source Type: research

Sarcopenia targeting with autophagy mechanism by exercise.
Abstract The loss of skeletal muscle, called sarcopenia, is an inevitable event during the aging process, and significantly impacts quality of life. Autophagy is known to reduce muscle atrophy caused by dysfunctional organelles, even though the molecular mechanism remains unclear. Here, we have discuss the current understanding of exercise-induced autophagy activation in skeletal muscle regeneration and remodeling, leading to sarcopenia intervention. With aging, dysregulation of autophagy flux inhibits lysosomal storage processes involved in muscle biogenesis. AMPK-ULK1 and the FoxO/PGC-1ɑ signaling pathways play...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Park SS, Seo YK, Kwon KS Tags: BMB Rep Source Type: research

Senotherapeutics: emerging strategy for healthy aging and age-related disease.
Abstract Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which k...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Kim EC, Kim JR Tags: BMB Rep Source Type: research

Cellular senescence: a promising strategy for cancer therapy.
Abstract Cellular senescence, a permanent state of cell cycle arrest is believed to have originally evolved to limit the proliferation of old or damaged cells. However, it has been recently shown that cellular senescence is a physiological and pathological program contributing to embryogenesis, immune response, and wound repair, as well as aging and age-related diseases. Unlike replicative senescence associated with telomere attrition, premature senescence rapidly occurs in response to various intrinsic and extrinsic insults. Thus, cellular senescence has also been considered suppressive mechanism of tumorigenesis...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Lee S, Lee JS Tags: BMB Rep Source Type: research

Cellular senescence in cancer.
Abstract Cellular senescence, a process of cell proliferation arrest in response to various stressors, has been considered to be important factor in age-related disease. Identification of senescent cells in tissues is limited and the role of senescent cells is poorly understood. Recently however, several studies showed the characterization of senescent cells in various pathologic conditions and the role of senescent cells in disease progression is becoming important. Senescent cells are growth-arrested cells, however, the senescence associated secretory phenotype (SASP) of senescent cells could modify the tissues'...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Kim YH, Park TJ Tags: BMB Rep Source Type: research

Multi-level remodeling of transcriptional landscapes in aging and longevity.
Abstract In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription...
Source: BMB Reports - December 11, 2018 Category: Biochemistry Authors: Lai R, Lu R, Danthi PS, Bravo J, Goumba A, Sampathkumar NK, Benayoun BA Tags: BMB Rep Source Type: research

CCAAT/enhancer-binding protein beta (C/EBP β) is an important mediator of 1,25 dihydroxyvitamin D3 (1,25D3)-induced receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts.
In conclusion, C/EBPβ is required for induction of RANKL by 1,25D3. PMID: 30355436 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - October 24, 2018 Category: Biochemistry Authors: Jo S, Lee YY, Han J, Lee YL, Yoon S, Lee J, Oh Y, Han JS, Sung IH, Park YS, Kim TH Tags: BMB Rep Source Type: research

Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex.
In this study, we selected two epitope peptide sequences within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero c...
Source: BMB Reports - October 24, 2018 Category: Biochemistry Authors: Park BK, Maharjan S, Lee SI, Kim J, Bae JY, Park MS, Kwon HJ Tags: BMB Rep Source Type: research

Protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride on hypoxia-induced β-amyloid production in SH-SY5Y cells.
Protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride on hypoxia-induced β-amyloid production in SH-SY5Y cells. BMB Rep. 2018 Oct 24;: Authors: Han AR, Yang JW, Na JM, Choi SY, Cho SW Abstract Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer's disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced β-amyloid (Aβ) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative,...
Source: BMB Reports - October 24, 2018 Category: Biochemistry Authors: Han AR, Yang JW, Na JM, Choi SY, Cho SW Tags: BMB Rep Source Type: research

Human Umbilical Cord Blood Plasma Alleviates Age-related Olfactory Dysfunction by Attenuating Peripheral TNF- α expression.
In this study, we investigated brain rejuvenation, particularly olfactory function, that could be achieved by a systemic administration of young blood and its underlying mechanisms. Older than 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, eight times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing time for finding foo...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Lee BC, Kang I, Lee SE, Lee JY, Shin N, Kim JJ, Choi SW, Kang KS Tags: BMB Rep Source Type: research

Interferon- γ-mediated Secretion of Tryptophanyl-tRNA Synthetases Has a Role in Protection of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells Against Experimental Colitis.
In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated CD4+ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and r...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Kang I, Lee BC, Lee JY, Kim JJ, Lee SE, Shin N, Choi SW, Kang KS Tags: BMB Rep Source Type: research

Overexpression of CXCL2 inhibits cell proliferation and promotes apoptosis in hepatocellular carcinoma.
We examined the expression levels of 7 types of ELR+ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Ding J, Xu K, Zhang J, Lin B, Wang Y, Yin S, Xie H, Zhou L, Zheng S Tags: BMB Rep Source Type: research

Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells.
Abstract Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Min DY, Jung E, Kim J, Lee YH, Shin SY Tags: BMB Rep Source Type: research

Enhanced Delivery of Protein Fused to Cell Penetrating Peptides to Mammalian Cells.
Abstract Recent progress in cellular reprogramming technology and lineage-specific cell differentiation has provided great opportunities for translational research. Because virus-based gene delivery is not a practical reprogramming protocol, protein-based reprogramming has been receiving attention as a safe way to generate reprogrammed cells. However, the poor efficiency of the cellular uptake of reprogramming proteins is still a major obstacle. Here, we reported key factors which improve the cellular uptake of these proteins. Purified red fluorescent proteins fused with 9xLysine (dsRED-9K) as a cell penetrating p...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Moon JI, Han MJ, Yu SH, Lee EH, Kim SM, Han K, Park CH, Kim CH Tags: BMB Rep Source Type: research

Functions of DEAD box RNA helicases DDX5 and DDX17 in chromatin organization and transcriptional regulation.
Abstract RNA helicases DDX5 and DDX17 are multitasking proteins that regulate gene expression in different biological contexts through diverse activities. Special attention has long been paid to their function as coregulators of transcription factors, providing insight about their functional association with a number of chromatin modifiers and remodelers. However, to date, the variety of described mechanisms has made it difficult to understand precisely how these proteins work at the molecular level, and the contribution of their ATPase domain to these mechanisms remains unclear as well. In light of their associat...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Giraud G, Terrone S, Bourgeois CF Tags: BMB Rep Source Type: research

Cellular machinery for sensing mechanical force.
Abstract For mechanical force to induce changes in cellular behaviors, two main processes are inevitable; perception of the force and response to it. Perception of mechanical force by cells, or mechanosensing, requires mechanical force-induced conformational changes in mechanosensors. For this, at least one end of the mechanosensors should be anchored to relatively fixed structures, such as extracellular matrices or the cytoskeletons, while the other end should be pulled along the direction of the mechanical force. Alternatively, mechanosensors may be positioned in lipid bilayers, so that conformational changes in...
Source: BMB Reports - October 8, 2018 Category: Biochemistry Authors: Lim CG, Jang J, Kim C Tags: BMB Rep Source Type: research

Cordycepin inhibits lipopolysaccharide-induced cell migration and invasion in human colorectal carcinoma HCT-116 cells through down-regulation of prostaglandin E2 receptor EP4.
Abstract Prostaglandin E2 (PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysa...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Jeong JW, Park C, Cha HJ, Hong SH, Park SH, Kim GY, Kim WJ, Kim CH, Song KS, Choi YH Tags: BMB Rep Source Type: research

MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD.
In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating NF-κB p65, and this may provide a novel therapeutic approach for TNBC. PMID: 30269739 [PubMed - as supplied by publisher] (Source: BMB Reports)
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Song H, Li D, Wu T, Xie D, Hua K, Hu J, Deng X, Ji C, Deng Y, Fang L Tags: BMB Rep Source Type: research

STK899704 inhibits stemness of cancer stem cells and migration via the FAK-MEK-ERK pathway in HT29 cells.
Abstract Colon cancer is one of the most lethal and common malignancies worldwide. STK899704, a novel synthetic agent, has been reported to exhibit anticancer effects towards numerous cancer cells. However, the effect of STK899704 on the biological properties of colon cancer, including cancer cell migration and cancer stem cells (CSCs), remains unknown. Here, we examined the inhibitory effect of STK899704 on cell migration and CSC stemness. In the wound healing assay, STK899704 significantly inhibited the motility of colon cancer cells. Furthermore, STK899704 downregulated the mRNA expression levels of the cell mi...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Jang HJ, Bak Y, Pham TH, Kwon SB, Kim BY, Hong J, Yoon DY Tags: BMB Rep Source Type: research

PEP-1-paraoxonase 1 fusion protein prevents cytokine-induced cell destruction and impaired insulin secretion in rat insulinoma cells.
In this study, we expressed the cell-permeable PON1 fused with PEP-1 protein transduction domain (PEP-1-PON1) to investigate whether transduced PEP-1-PON1 protects beta cells against cytokine-induced cytotoxicity. PEP-1-PON1 was effectively delivered to INS-1 cells and prevented cytokine-induced cell destruction in a dose-dependent manner. Transduced PEP-1-PON1 significantly reduced the levels of reactive oxygen species (ROS) and nitric oxide (NO), DNA fragmentation, and expression of inflammatory mediators, endoplasmic reticulum (ER) stress proteins, and apoptosis-related proteins in cytokine-treated cells. Moreover, tran...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Lee SJ, Kang HK, Choi YJ, Eum WS, Park J, Choi SY, Kwon HY Tags: BMB Rep Source Type: research

MicroRNA controls of cellular senescence.
Abstract Cellular senescence is a state of permanent cell-cycle arrest triggered by different internal and external stimuli. This phenomenon is considered to be both beneficial and detrimental depending on the cell types and biological contexts. During normal embryonic development and after tissue injury, cellular senescence is critical for tissue remodeling. In addition, this process is useful for arresting growth of tumor cells, particularly during early onset of tumorigenesis. However, accumulation of senescent cells decreases tissue regenerative capabilities and induces inflammation, which is responsible for c...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Suh N Tags: BMB Rep Source Type: research

Regulation of RIP3 Protein Stability by PELI1-mediated Proteasome-Dependent Degradation.
Abstract Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is a serine-threonine kinase largely essential for necroptotic cell death; it also plays a role in some inflammatory diseases. High levels of RIP3 are likely sufficient to activate necroptotic and inflammatory pathways downstream of RIP3 in the absence of an upstream stimulus. For example, we have previously detected high levels or RIP3 in the skin of Toxic Epidermal Necrolysis patients; this correlates with increased phosphorylation of MLKL found in these patients. We have long surmised that there are molecular mechanisms to prevent anomalous activity...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Park HH, Morgan MJ, Kang HC, Kim YS Tags: BMB Rep Source Type: research

Roles of mitochondria in neuronal development.
Abstract Mitochondria are ubiquitous and multi-functional organelles involved in diverse metabolic processes, namely energy production and biomolecule synthesis. The intracellular mitochondrial morphology and distribution change dynamically, which reflect the metabolic state of a given cell type. A dramatic change of the mitochondrial dynamics has been observed in early development that led to further investigations on the relationship between mitochondria and the process of development. A significant developmental process to focus on, in this review, is a differentiation of neural progenitor cells into neurons. I...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Son G, Han J Tags: BMB Rep Source Type: research

The origin-of-cell harboring cancer-driving mutations in human glioblastoma.
Abstract Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in h...
Source: BMB Reports - October 1, 2018 Category: Biochemistry Authors: Lee JH, Lee JH Tags: BMB Rep Source Type: research

Downregulated MicroRNAs in the Colorectal Cancer: Diagnostic and Therapeutic Perspectives.
Prados J, Rama AR Abstract Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcrip...
Source: BMB Reports - August 30, 2018 Category: Biochemistry Authors: Hernández R, Sánchez-Jiménez E, Melguizo C, Prados J, Rama AR Tags: BMB Rep Source Type: research

Renal protective effects of zingerone in a mouse model of sepsis.
This study was initiated to determine whether ZGR could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of ZGR treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with ZGR resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, ZGR ...
Source: BMB Reports - August 30, 2018 Category: Biochemistry Authors: Lee BS, Lee C, Yang S, Ku SK, Bae JS Tags: BMB Rep Source Type: research

Role of the CCN Protein Family in Cancer.
Abstract The CCN protein family is composed of six matricellular proteins, which serve regulatory roles rather than structural roles in the extracellular matrix. First identified as secreted proteins which are induced by oncogenes, the acronym CCN came from the names of the first three members: CYR61, CTGF, and NOV. All six members of the CCN family consist of four cysteine-rich modular domains. CCN proteins are known to regulate cell adhesion, proliferation, differentiation, and apoptosis. In addition, CCN proteins are associated with cardiovascular and skeletal development, injury repair, inflammation, and cance...
Source: BMB Reports - August 30, 2018 Category: Biochemistry Authors: Kim H, Son S, Shin I Tags: BMB Rep Source Type: research

Recent insights into the role of ChREBP in intestinal fructose absorption and metabolism.
Abstract Fructose in the form of sucrose and high fructose corn syrup is absorbed by the intestinal transporter and mainly metabolized in the small intestine. However, excess intake of fructose overwhelms the absorptive capacity of the small intestine, leading to fructose malabsorption. Carbohydrate response element-binding protein (ChREBP) is a basic helix-loop-helix leucine zipper transcription factor that plays a key role in glycolytic and lipogenic gene expression in response to carbohydrate consumption. While ChREBP was initially identified as a glucose-responsive factor in the liver, recent evidence suggests...
Source: BMB Reports - August 30, 2018 Category: Biochemistry Authors: Lee HJ, Cha JY Tags: BMB Rep Source Type: research

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