bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulated microgravity‐induced epigenetic changes in human lymphocytes
Authors: Singh Kamaleshwar P. , Kumari Ragini , DuMond James W. 
Published: May 2010

AbstractReal space flight and modeled microgravity conditions result in changes in the expression of genes that control important cellular functions. However, the mechanisms for microgravity‐induced gene expression changes are not clear. The epigenetic changes of DNA methylation and chromatin histones modifications are known to regulate gene expression. The objectives of this study were to investigate whether simulated microgravity alters (a) the DNA methylation and histone acetylation, and (b) the expression of DNMT1, DNMT3a, DNMT3b, and HDAC1 genes that regulate epigenetic events. To achieve these objectives, human T‐lymphocyte cells were grown in a rotary cell culture system (RCCS) that simulates microgravity, and in parallel under normal gravitational conditions as control. The microgravity‐induced DNA methylation changes were detected by methylation sensitive‐random amplified polymorphic DNA (MS‐RAPD) analysis of genomic DNA. The gene expression was measured by Quantitative Real‐time PCR. The expression of DNMT1, DNMT3a, and DNMT3b was found to be increased at 72 h, and decreased at 7 days in microgravity exposed cells. The MS‐RAPD analysis revealed that simulated microgravity exposure results in DNA hypomethylation and mutational changes. Gene expression analysis revealed microgravity exposure time‐dependent decreased expression of HDAC1. Decreased expression of HDAC1 should result in increased level of acetylated histone H3, however a decreased level of acetylated H3 was observed in microgravity condition, indicating thereby that other HDACs may be involved in regulation of H3 deacetylation. The findings of this study suggest that epigenetic events could be one of the mechanistic bases for microgravity‐induced gene expression changes and associated adverse health effects. J. Cell. Biochem. 111: 123–129, 2010. © 2010 Wiley‐Liss, Inc.
Involvement of integrin up‐regulation in RANKL/RANK pathway of chondrosarcomas migration
Authors: Hsu Chin‐Jung , Lin Tsang‐Yu , Kuo Chien‐Chung , Tsai Chun‐Hao , Lin Mou‐Zen , Hsu Horng‐Chaung , Fong Yi‐Chin , Tang Chih‐Hsin 
Published: May 2010

AbstractInvasion of tumor cells is the primary cause of therapeutic failure in malignant chondrosarcomas treatment. Receptor activator of nuclear factor‐κB ligand (RANKL) and its receptor, RANK, play a key roles in osteoclastogenesis and tumor metastasis. We found that the RANKL and RANK expression in human chondrosarcoma tissues was higher than that in normal cartilage. We also found that RANKL directed the migration and increased cell surface expression of β1 integrin in human chondrosarcoma cells (JJ012 cells). Pretreatment of JJ012 cells with MAPK kinase (MEK) inhibitors, PD98059 or U0126, inhibited the RANKL‐induced migration and integrin expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal‐regulating kinase (ERK). In addition, NF‐κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited RANKL‐induced cells migration and integrin up‐regulation. Taken together, these results suggest that the RANKL acts through MEK/ERK, which in turn activates IKKα/β and NF‐κB, resulting in the activation of β1 integrin and contributing to the migration of human chondrosarcoma cells. J. Cell. Biochem. 111: 138–147, 2010. © 2010 Wiley‐Liss, Inc.
The IGF‐I regulatory system and its impact on skeletal and energy homeostasis
Authors: Kawai Masanobu , Rosen Clifford J. 
Published: May 2010

AbstractInsulin‐like growth factor (IGF)‐I is important in the acquisition and maintenance of both soft and hard tissues. Skeletal remodeling requires energy and recent work has demonstrated that bone can influence insulin sensitivity and thereby regulate metabolic processes. New insights from mouse models into the role of IGF‐binding proteins (IGFBPs) as more than mere depots for the IGFs has reignited investigations into the metabolic targets influenced by the IGF regulatory system and the pathways that link bone to adipose tissue. Although there remains continued uncertainty about the relative balance between the effects of circulating versus tissue IGF‐I actions, the role of the IGFBPs has been redefined both as modulators of IGF‐I action and as independent signaling factors. This review highlights several recent findings that shed new light on the physiologic role of the IGF regulatory system and its influence on skeletal and fat metabolism. J. Cell. Biochem. 111: 14–19, 2010. © 2010 Wiley‐Liss, Inc.
Potential role of branched‐chain amino acids in glucose metabolism through the accelerated induction of the glucose‐sensing apparatus in the liver
Authors: Higuchi Nobito , Kato Masaki , Miyazaki Masayuki , Tanaka Masatake , Kohjima Motoyuki , Ito Tetsuhide , Nakamuta Makoto , Enjoji Munechika , Kotoh Kazuhiro , Takayanagi Ryoichi 
Published: May 2010

AbstractBranched‐chain amino acids (BCAAs) have a potential to improve glucose metabolism in cirrhotic patients; however, the contribution of liver in this process has not been clarified. To estimate the effect of BCAA on glucose metabolism in liver, we evaluated the mRNA expression levels of glucose‐sensing apparatus genes in HepG2 cells and in rat liver after oral administration of BCAA. HepG2 cells were cultured in low glucose (100 mg/dl) or high glucose (400 mg/dl) in the absence or presence of BCAA. The mRNA expression levels and protein levels of GLUT2 and liver‐type glucokinase (L‐GK) were estimated using RT‐PCR and immunoblotting. The expression levels of transcriptional factors, including SREBP‐1c, ChREBP, PPAR‐γm and LXRα, were estimated. The mRNA expression levels of transcriptional factors, glycogen synthase, and genes involved in gluconeogenesis were evaluated in rat liver at 3 h after the administration of BCAA. BCAA accelerated the expression of GLUT2 and L‐GK in HepG2 cells in high glucose. Expression levels of ChREBP, SREBP‐1c, and LXRα were also increased in this condition. BCAA administration enhanced the mRNA expression levels of L‐GK, SREBP‐1c, and LXRα and suppressed the expression levels of G‐6‐Pase in rat liver, without affecting the expression levels of glycogen synthase or serum glucose concentrations. BCAA administration enhanced the bioactivity of the glucose‐sensing apparatus, probably via the activation of a transcriptional mechanism, suggesting that these amino acids may improve glucose metabolism through the accelerated utility of glucose and glucose‐6‐phosphate in the liver. J. Cell. Biochem. 112: 30–38, 2011. © 2010 Wiley‐Liss, Inc.
PTEN‐ and p53‐mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice
Authors: Zheng Tongsen , Meng Xianzhi , Wang JiaBei , Chen Xi , Yin Dalong , Liang Yingjian , Song Xuan , Pan Shangha , Jiang Hongchi , Liu Lianxin 
Published: May 2010

AbstractFTY720, a new immunosuppressant, derived from ISP‐1, has been studied for its putative anti‐cancer properties in the recent years. In this study, we have reported that FTY720 greatly inhibited gastric cancer cell proliferation for the first time, and found this effect was associated with G1 phase cell cycle arrest and apoptosis. Results from our Western blotting and Real‐time PCR showed that FTY720 induced obvious PTEN expression in a p53‐independent way, consistent with a substantial decrease in p‐Akt and MDM2. FTY720 dramatically increased the expression of Cip1/p21, p27, and BH3‐only proteins through the accumulation of p53 by PTEN‐mediated inhibition of the PI3K/Akt/MDM2 signaling. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt, resulting in decreased apoptosis and increased cell survival. Furthermore, we have observed an additive effect of FTY720 in killing gastric cancer cells when in combination with Cisplatin, partly through PTEN‐mediated Akt/MDM2 inhibition. In vivo study has also shown that tumor growth was significantly suppressed after FTY720 treatment. In conclusion, our results suggest that FTY720 induces a significant increase of PTEN, which inhibits p‐Akt and MDM2, and then increases the level of p53, thereby inducing G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, for the first time, which shows potential anti‐tumor effects on gastric cancer by PTEN activation through p53‐independent mechanism, especially in combination with Cisplatin. This PTEN target‐based therapy is worth further investigation and warrants clinical evaluation. J. Cell. Biochem. 111: 218–228, 2010. © 2010 Wiley‐Liss, Inc.
Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoietic progenitor cell proliferation and function
Authors: Chitteti Brahmananda R. , Cheng Ying‐Hua , Streicher Drew A. , Rodriguez‐Rodriguez Sonia , Carlesso Nadia , Srour Edward F. , Kacena Melissa A. 
Published: May 2010

AbstractAlthough osteoblasts (OB) play a key role in the hematopoietic stem cell (HSC) niche, little is known as to which specific OB lineage cells are critical for the enhancement of stem and progenitor cell function. Unlike hematopoietic cells, OB cell surface phenotypic definitions are not well developed. Therefore, to determine which OB lineage cells are most important for hematopoietic progenitor cell (HPC) function, we characterized OB differentiation by gene expression and OB function, and determined whether associations existed between OB and HPC properties. OB were harvested from murine calvariae, used immediately (fresh OB) or cultured for 1, 2, or 3 weeks prior to their co‐culture with Lin−Sca1+c‐kit+ (LSK) cells for 1 week. OB gene expression, alkaline phosphatase activity, calcium deposition, hematopoietic cell number fold increase, CFU fold increase, and fold increase of Lin−Sca1+ cells were determined. As expected, HPC properties were enhanced when LSK cells were cultured with OB compared to being cultured alone. Initial alkaline phosphatase and calcium deposition levels were significantly and inversely associated with an increase in the number of LSK progeny. Final calcium deposition levels and OB culture duration were inversely associated with all HPC parameters, while Runx2 levels were positively associated with all HPC properties. Since calcium deposition is associated with OB maturation and high levels of Runx2 are associated with less mature OB lineage cells, these results suggest that less mature OB better promote HPC proliferation and function than do more mature OB. J. Cell. Biochem. 111: 284–294, 2010. © 2010 Wiley‐Liss, Inc.
Calnexin inhibits thermal aggregation and neurotoxicity of prion protein
Authors: Wang Wenxi , Chen Rui , Luo Kan , Wu Di , Huang Liqin , Huang Tao , Xiao Gengfu 
Published: May 2010

AbstractPrion diseases are fatal neurodegenerative disorder associated with the conversion of the cellular isoform of the prion protein (PrPC) into the infectious scrapie isoform (PrPSc). Deposition of misfolded prion proteins (PrP) on certain regions of brain can result in prion diseases. As a membrane‐bound chaperone of the endoplasmic reticulum (ER), calnexin ensures the proper folding and quality control of newly synthesized proteins. Using purified components in vitro, calnexin associated with many proteins and suppresses their thermal aggregation effectively. We for the first time analyzed PrP‐calnexin interaction. The immunoprecipitation, confocal microscope and native polyacrylamide‐gel electrophoresis results indicated that calnexin could bind PrP both in vitro and in vivo. The turbidity result showed that calnexin could supress thermal aggregation of PrP. MTT, flow cytometry (FCM) and caspase activity studies demonstrated that calnexin prevent caspase‐3‐mediated cytotoxicity induced by PrP. These results implied that calnexin is potentially beneficial for the resistance of prion diseases. J. Cell. Biochem. 111: 343–349, 2010. © 2010 Wiley‐Liss, Inc.
Intestinal stem cell asymmetric division in the Drosophila posterior midgut
Authors: Hou Steven X. 
Published: May 2010

AbstractOver the past 2 years, our understanding of intestinal stem cells in the Drosophila posterior midgut has advanced greatly. In this review, I will focus on the establishment of these stem cells in their niche during development and the molecular mechanisms that regulate their asymmetric division in adults. J. Cell. Physiol. 224: 581–584, 2010. Published 2010 Wiley‐Liss, Inc.
Extracellular calcium sensing receptor stimulation in human colonic epithelial cells induces intracellular calcium oscillations and proliferation inhibition
Authors: Rey Osvaldo , Young Steven H. , Jacamo Rodrigo , Moyer Mary P. , Rozengurt Enrique 
Published: May 2010

AbstractThe extracellular Ca2+‐sensing receptor (CaR) is increasingly implicated in the regulation of multiple cellular functions in the gastrointestinal tract, including secretion, proliferation and differentiation of intestinal epithelial cells. However, the signaling mechanisms involved remain poorly defined. Here we examined signaling pathways activated by the CaR, including Ca2+ oscillations, in individual human colon epithelial cells. Single cell imaging of colon‐derived cells expressing the CaR, including SW‐480, HT‐29, and NCM‐460 cells, shows that stimulation of this receptor by addition of aromatic amino acids or by an elevation of the extracellular Ca2+ concentration promoted striking intracellular Ca2+ oscillations. The intracellular calcium oscillations in response to extracellular Ca2+ were of sinusoidal pattern and mediated by the phospholipase C/diacylglycerol/inositol 1,4,5‐trisphosphate pathway as revealed by a biosensor that detects the accumulation of diacylglycerol in the plasma membrane. The intracellular calcium oscillations in response to aromatic amino acids were of transient type, that is, Ca2+ spikes that returned to baseline levels, and required an intact actin cytoskeleton, a functional Rho, Filamin A and the ion channel TRPC1. Further analysis showed that re‐expression and stimulation of the CaR in human epithelial cells derived from normal colon and from colorectal adenocarcinoma inhibits their proliferation. This inhibition was associated with the activation of the signaling pathway that mediates the generation of sinusoidal, but not transient, intracellular Ca2+ oscillations. Thus, these results indicate that the CaR can function in two signaling modes in human colonic epithelial cells offering a potential link between gastrointestinal responses and food/nutrients uptake and metabolism. J. Cell. Physiol. 225: 73–83, 2010. © 2010 Wiley‐Liss, Inc.
Differentiated human adipose‐derived stem cells exhibit hepatogenic capability in vitro and in vivo
Authors: Ruiz Joseph C. , Ludlow John W. , Sherwood Sonya , Yu Gang , Wu Xiying , Gimble Jeffrey M. 
Published: May 2010

AbstractThe availability of suitable human livers for transplantation falls short of the number of potential patients. In addition, the availability of primary human hepatocytes for cell‐therapy and drug development applications is significantly limited; less than 700 livers per year are available for such studies. However, the majority of these organs cannot be utilized due to pathological infections (e.g., HepB, HepC, or HIV) or excessive levels of steatosis. Thus, the number of cells needed for cell therapy applications far exceeds the number of cells available from donated livers. The ability to implant progenitor cell populations that can form liver tissue in situ, or can be differentiated in vitro would be a major advance in current cell‐based therapies. In addition, and importantly for this application, the ability to utilize a non‐hepatic progenitor cell to mimic hepatocytes in vitro would enable the scale‐up production of cells for bioartifical liver assist devices, cell‐therapy and drug discovery applications. We demonstrate the feasibility of inducing adipose‐derived stromal (ASC) cells to express several features of human hepatocytes such as glycogen storage and expression of liver specific genes. Importantly, we also show that undifferentiated ASCs and ASC‐derived hepatic cells engraft robustly into the liver in a mouse model of toxic injury. These data indicate a significant potential for the use of undifferentiated ASCs and ASC‐derived hepatic cells as novel and valuable products for cell therapy. J. Cell. Physiol. 225: 429–436, 2010. © 2010 Wiley‐Liss, Inc.
MicroRNAs are dynamically regulated in hypertrophic hearts, and miR‐199a is essential for the maintenance of cell size in cardiomyocytes
Authors: Song Xiao‐Wei , Li Qing , Lin Li , Wang Xiao‐Chen , Li Dong‐Feng , Wang Guo‐Kun , Ren An‐Jing , Wang Yan‐Rong , Qin Yong‐Wen , Yuan Wen‐Jun , Jing Qing 
Published: May 2010

AbstractCardiac hypertrophy, which is characterized by an increase in cell size and reactivation of fetal genes, occurs as an adaptive response to diverse forms of stress and often results in heart failure and sudden death. Growing evidence indicates that microRNAs (miRNAs) are involved in cardiac hypertrophy, but the function of these miRNAs remains elusive. Here, using real time PCR analysis, we showed that several miRNAs were dynamically regulated in the rat hypertrophic hearts and miR‐199a was up‐regulated by 10‐fold in hypertrophic hearts after abdominal aorta constriction for 12 weeks. With tissue profiling analysis, we showed that miR‐199a was predominantly expressed in cardiomyocytes, but was also faintly detected in cardiac fibroblasts. To investigate whether miR‐199a was involved in cardiac hypertrophy, both over‐expression and knockdown of miR‐199a were performed in cultured cardiomyocytes. Over‐expression of miR‐199a in cardiomyocytes increased the cell size as measured by cell surface area, and also reduced the mRNA expression level of α‐myosin heavy chain. In accordance, knockdown of endogenous miR‐199a in cardiomyocytes reduced the cell size. Down‐regulation of miR‐199a also attenuated the phenylephrine‐induced increase of cell size. Furthermore, bioinformatic algorithms were used to predict the potential targets of miR‐199a in cardiac hypertrophy, and hypoxia‐inducible factor 1 alpha was confirmed by the luciferase reporter assay to be a potential target of miR‐199a. Taken together, our results demonstrated that miR‐199a, which was predominantly expressed in cardiomyocytes, was essential for the maintenance of cell size of cardiomyocytes and might play a role in the regulation of cardiac hypertrophy. J. Cell. Physiol. 225: 437–443, 2010. © 2010 Wiley‐Liss, Inc.
Impaired muscle regeneration and myoblast differentiation in mice with a muscle‐specific KO of IGF‐IR
Authors: Heron‐Milhavet Lisa , Mamaeva Daria , LeRoith Derek , Lamb Ned J. , Fernandez Anne 
Published: May 2010

AbstractIGF‐I and its receptor IGF‐IR are seen as critical effectors of muscle hypertrophy, a notion recently questioned. Using MKR transgenic mice that express a dominant negative IGF‐IR only in skeletal muscle, we have examined the role of the IGF‐IR signaling in differentiation and repair of muscle fibers after damage‐induced muscle regeneration. This process is impaired in MKR muscle, with incomplete regeneration, persistence of infiltrating cells and sustained expression of differentiation markers. Analysis of MKR and WT muscle‐derived progenitor stem cells and myoblasts showed twice as many such cells in MKR muscle and an incomplete in vitro differentiation, that is, despite similar levels of myogenin expression, the level of fusion of MKR myoblasts was significantly reduced in comparison to WT myoblasts. These data show IGF‐IR signaling is not only required at early hyperplasia stages of muscle differentiation, but also for late stages of myofiber maturation and hypertrophy. J. Cell. Physiol. 225: 1–6, 2010. © 2010 Wiley‐Liss, Inc.
Cell shape and TGF‐β signaling define the choice of lineage during in vitro differentiation of mouse primary hepatic precursors
Authors: Akkari Leila , Haouzi Delphine , Binamé Fabien , Floc'h Nicolas , Lassus Patrice , Baghdiguian Stephen , Hibner Urszula 
Published: May 2010

AbstractCellular differentiation relies on both physical and chemical environmental cues. The bipotential mouse embryonic liver (BMEL) cells are early progenitors of liver epithelial cells with an apparently infinite proliferative potential. These cells, which remain undifferentiated in a monolayer culture, differentiate upon release from geometrical constraints imposed by growth on a stiff plastic plate. In a complex three dimensional environment of a Matrigel extracellular matrix, BMEL cells form two types of polarized organoids of distinct morphologies: cyst‐like structures suggesting cholangiocyte‐type organization or complex organoids, reminiscent of liver parenchyma and associated with acquisition of hepatocyte‐specific phenotypic markers. The choice of the in vitro differentiation lineage is governed by Transforming Growth Factor‐β (TGF‐β) signaling. Our results suggest that morphological cues initiate the differentiation of early hepatic precursors and confirm the inhibitory role of TGF‐β on hepatocytic lineage differentiation. J. Cell. Physiol. 225: 186–195, 2010. © 2010 Wiley‐Liss, Inc.
12‐O‐tetradecanoylphorbol‐13‐acetate‐induced invasion/migration of glioblastoma cells through activating PKCα/ERK/NF‐κB‐dependent MMP‐9 expression
Authors: Lin Cheng‐Wei , Shen Shing‐Chuan , Chien Chih‐Chiang , Yang Liang‐Yo , Shia Lin‐Ting , Chen Yen‐Chou 
Published: May 2010

AbstractAn increase in MMP‐9 gene expression and enzyme activity with stimulating the migration of GBM8401 glioma cells via wound healing assay by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) was detected in glioblastoma cells GBM8401. TPA‐induced translocation of protein kinase C (PKC)α from the cytosol to membranes, and migration of GBM8401 elicited by TPA was suppressed by adding the PKCα inhibitors, GF109203X and H7. Activation of extracellular signal‐regulated kinase (ERK) and c‐Jun‐N‐terminal kinase (JNK) by TPA was identified, and TPA‐induced migration and MMP‐9 activity was significantly blocked by ERK inhibitor PD98059 and U0126, but not JNK inhibitor SP600125. Activation of NF‐κB protein p65 nuclear translocation and IκBα protein phosphorylation with increased NF‐κB‐directed luciferase activity by TPA were observed, and these were blocked by the PD98059 and IkB inhibitor BAY117082 accompanied by reducing migration and MMP‐9 activity induced by TPA in GBM8401 cells. Transfection of GBM8401 cells with PKCα siRNA specifically reduced PKCα protein expression with blocking TPA‐induced MMP‐9 activation and migration. Additionally, suppression of TPA‐induced PKCα/ERK/NK‐κB activation, migration, and MMP‐9 activation by flavonoids including kaempferol (Kae; 3,5,7,4′‐tetrahydroxyflavone), luteolin (Lut; 5,7,3′4′‐tetrahydroxyflavone), and wogonin (Wog; 5,7‐dihydroxy‐8‐methoxyflavone) was demonstrated, and structure–activity relationship (SAR) studies showed that hydroxyl (OH) groups at C4′ and C8 are critical for flavonoids' action against MMP‐9 enzyme activation and migration/invasion of glioblastoma cells elicited by TPA. Application of flavonoids to prevent the migration/invasion of glioblastoma cells through blocking PKCα/ERK/NF‐κB activation is first demonstrated herein. J. Cell. Physiol. 225: 472–481, 2010. © 2010 Wiley‐Liss, Inc.