bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nerve growth factor promotes differentiation of odontoblast‐like cells
Authors: Arany Szilvia , Koyota Souichi , Sugiyama Toshihiro 
Published: January 2009

AbstractContemporary strategies in tooth repair markedly rely on the newest findings on the cellular and biological components of dental development. Among several identified bioactive molecules, neurotrophins were recently proposed to affect tooth germ cell proliferation, differentiation, and cell–extracellular matrix interactions. The present study attempted to explore the effect of nerve growth factor (NGF) on a spontaneously immortalized dental papilla mesenchymal cell line. NGF induced differentiation of odontoblast‐lineage cells with subsequent biomineralization in vitro. Here we showed that normalized transcript levels of tissue‐specific markers such as DSPP and DMP1 were elevated significantly, indicating cell differentiation and maturation processes. We performed innovative gene expression analysis of TM14, a matricellular protein and novel member of the fibulin family. TM14 expression followed a pattern similar to that of DMP1, which suggests its important role in cell–matrix and intercellular interactions during dentin calcification. Alkaline phosphatase enzyme assay confirmed the extracellular matrix calcifications in NGF‐supplemented groups. Thus, NGF was characterized as a potent promoter of mineralization during dentin formation. For the first time, we included TM14 in odontoblast genotype analysis and proved that NGF also promotes in vitro odontoblast differentiation. Collectively, these results highlight the importance of NGF during tooth morphogenesis, as well as urge the elaboration of complex epithelial–mesenchymal tissue cultures, where further elucidation of the signaling factor network could be completed. J. Cell. Biochem. 106: 539–545, 2009. © 2009 Wiley‐Liss, Inc.
Gastrointestinal pathology in a mouse model of mucopolysaccharidosis type IIIA
Authors: Roberts Ainslie L.K. Derrick , Howarth Gordon S. , Liaw Wan Chin , Moretta Simon , Kritas Stamatiki , Lymn Kerry A. , Yazbeck Roger , Tran Cuong , Fletcher Janice M. , Butler Ross N. , Byers Sharon 
Published: January 2009

AbstractMucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by a deficiency in sulphamidase (NS), a lysosomal enzyme required for the degradation of heparan sulphate glycosaminoglycans (gags). The MPS IIIA mouse is a naturally occurring model that accurately reflects the human pathology and disease course. It displays primarily central nervous system pathology accompanied by widespread accumulation of gag in somatic tissues. MPS IIIA mice exhibit greater bodyweight gain than normal littermates and attain a higher mature bodyweight. In this study, gastrointestinal morphology and function was characterised in the IIIA mouse. Stomach and duodenum weight increased in MPS IIIA mice and duodenum length also increased. An increased submucosal thickness was observed in MPS IIIA intestine compared to normal mice and lysosomal storage of gag was observed in this region. Storage was also observed in the lamina propria of the villus tip. All other morphometric measurements including villus height and crypt depth fell within the normal range. The gastric emptying half‐life of solid and liquid meals decreased with age in normal mice whereas the T½ of solid meals did not alter with age in MPS IIA mice such that they were elevated above normal by 38 weeks of age. Sucrase activity was higher than normal in MPS IIIA at all ages tested. These abnormalities in GI structure and function observed in MPS IIIA may contribute to weight gain in this disorder. J. Cell. Physiol. 219: 259–264, 2009. © 2009 Wiley‐Liss, Inc.
CDK inhibitors selectively diminish cell cycle controlled activation of the histone H4 gene promoter by p220NPAT and HiNF‐P
Authors: Mitra Partha , Ghule Prachi N. , van der Deen Margaretha , Medina Ricardo , Xie Rong‐lin , Holmes William F. , Ye Xin , Nakayama Keiichi I. , Harper J. Wade , Stein Janet L. , Stein Gary S. , van Wijnen Andre J. 
Published: January 2009

AbstractCell cycle progression into S phase requires the induction of histone gene expression to package newly synthesized DNA as chromatin. Cyclin E stimulation of CDK2 at the Restriction point late in G1 controls both histone gene expression by the p220NPAT/HiNF‐P pathway and initiation of DNA replication through the pRB/E2F pathway. The three CDK inhibitors (CKIs) p21CIP1/WAF1, p27KIP1, and p57KIP2 attenuate CDK2 activity. Here we find that γ‐irradiation induces p21CIP1/WAF1 but not the other two CKIs, while reducing histone H4 mRNA levels but not histone H4 gene promoter activation by the p220NPAT/HiNF‐P complex. We also show that p21CIP1/WAF1 is less effective than p27KIP1 and p57KIP2 in inhibiting the CDK2 dependent phosphorylation of p220NPAT at subnuclear foci and transcriptional activation of histone H4 genes. The greater effectiveness of p57KIP2 in blocking the p220NPAT/HiNF‐P pathway is attributable in part to its ability to form a specific complex with p220NPAT that may suppress CDK2/cyclin E phosphorylation through direct substrate inhibition. We conclude that CKIs selectively control stimulation of the histone H4 gene promoter by the p220NPAT/HiNF‐P complex. J. Cell. Physiol. 219: 438–448, 2009. © 2009 Wiley‐Liss, Inc.
Cytotoxicity induced by inhibition of thioredoxin reductases via multiple signaling pathways: Role of cytosolic phospholipase A2α‐dependent and ‐independent release of arachidonic acid
Authors: Kurosawa Takeshi , Nakamura Hiroyuki , Yamaura Erika , Fujino Hiromichi , Matsuzawa Yasuo , Kawashima Tatsuo , Murayama Toshihiko 
Published: January 2009

AbstractThe thioredoxin (Trx) system, comprising Trx, the selenoprotein thioredoxin reductase (TrxR), and NADPH, functions as an antioxidant system. Trx has various biological activities including growth control and anti‐apoptotic properties, and the Trx system offers a target for the development of drugs to treat and/or prevent cancer. We evaluated the role of TrxR inhibition in the release of arachidonic acid (AA), cell toxicity, and intracellular signaling pathways in L929 mouse fibrosarcoma cells. Treatment with 1‐chloro‐2,4‐dinitrobenzene (DNCB, an inhibitor of TrxR) under conditions involving limited inhibition of TrxR activity in cells, released AA before causing cytotoxicity. Treatment with an inhibitor of p38 kinase, a downstream enzyme of the apoptosis signal‐regulating kinase 1 pathway, and pyrrophenone (an inhibitor of α‐type cytosolic phospholipase A2, cPLA2α) partially but significantly decreased the DNCB‐induced release of AA and cell death. The responses were much weaker in cPLA2α knockdown L929 cells. Exogenously added AA showed cytotoxicity. DNCB increased intracellular reactive oxygen species (ROS) levels, and butylated hydroxyanisole (an antioxidant) reduced DNCB‐induced ROS formation and cell toxicity but not the phosphorylation of p38 kinase and release of AA. Auranofin, another inhibitor of TrxR having a different formula, released AA resulting in toxicity in L929 cells. DNCB caused the release of AA and cytotoxicity in A549 human lung carcinoma cells, and caused p38 kinase‐dependent toxicity in PC12 rat pheochromocytoma cells. Our data suggest that a dysfunctional Trx system triggers multiple signaling pathways, and that the AA released by cPLA2α‐dependent and ‐independent pathways is important to cytotoxicity. J. Cell. Physiol. 219: 606–616, 2009. © 2009 Wiley‐Liss, Inc.
Thyroid hormone treatment of cultured chondrocytes mimics in vivo stimulation of collagen X mRNA by increasing BMP 4 expression
Authors: Lassová Luisa , Niu Zeling , Golden Eleanor B. , Cohen Arthur J. , Adams Sherrill L. 
Published: January 2009

AbstractDuring endochondral bone formation, chondrocytes undergo terminal differentiation, during which the rate of proliferation decreases, cells become hypertrophic, and the extracellular matrix is altered by production of collagen X, as well as proteins required for matrix mineralization. This maturation process is responsible for most longitudinal bone growth, both during embryonic development and in postnatal long bone growth plates. Among the major signaling molecules implicated in regulation of this process are the positive regulators thyroid hormone (T3) and bone morphogenetic proteins (BMPs). Both T3 and BMPs are essential for endochondral bone formation and cannot compensate for each other, suggesting interaction of the two signaling pathways. We have analyzed the temporal and spatial expression patterns of numerous genes believed to play a role in chondrocyte maturation. Our results show that T3 stimulates collagen X gene expression in cultured chondrocytres with kinetics and magnitude similar to those observed in vivo. Stimulation of collagen X gene expression by T3 occurs only after a significant delay, implying that this hormone may act indirectly. We show further that T3 rapidly stimulates production of BMP 4, concomitant with a decrease in the BMP inhibitor Noggin, potentially resulting in a net increase in BMP signaling. Finally, inhibition of BMP signaling with exogenous Noggin prevents T3 stimulation of collagen X expression, indicating that BMP signaling is essential for this process. These data position thyroid hormone at the top of a T3/BMP cascade, potentially explaining why both pathways are essential for chondrocyte maturation. J. Cell. Physiol. 219: 595–605, 2009. © 2009 Wiley‐Liss, Inc.
p53‐mediated regulation of cell cycle progression: Pronounced impact of cellular microenvironment
Authors: Schmid Gerald , Kramer Matthias P. , Węsierska‐Gądek Józefa 
Published: January 2009

AbstractData on the biological effects of some overexpressed oncogenes and their cooperation with cellular factors are, at least partially, contradictory. There are reports on the strong pro‐apoptotic action of temperature‐sensitive (ts) p53135val in transformed cells at permissive temperature. However, in our experience very high levels of p53135val induce in transformed rat cells at permissive temperature cell cycle arrest but not apoptosis. Comparison of the experimental protocols reveals that cells used for transfection strongly differ. Therefore, we decided to explore the impact of primary cells used for generation of cell clones on the biological effects evoked by p53 and c‐Ha‐Ras. In the present study, we used primary rat cells (RECs) isolated from rat embryos of different age: at 13.5 gd (y) and 15.5 gd (o). We immortalized rat cells using ts p53135val mutant and additionally generated transformed cells after co‐transfection with oncogenic Ras. The RECs were transfected with a constitutively activated Ha‐Ras protein, a mutation that is found in a wide variety of human tumors. The ts p53135Val mutant, switching between wild‐type (wt) and mutant conformation, offers the possibility to study the escape from p53‐mediated cell cycle control in a model of malignant transformation in cells with the same genetic background. Surprisingly, the kinetics of cell proliferation at non‐permissive temperature and that of cell cycle arrest at 32°C strongly differed between cell clones established from yRECs and oRECs, thereby indicating that overexpression of genes such as ts p53135Val mutant and oncogenic‐Ha‐Ras does not fully override the intrinsic cellular program. J. Cell. Physiol. 219: 459–469, 2009. © 2009 Wiley‐Liss, Inc.
Prolactin's role in the early stages of liver regeneration in rats
Authors: Olazabal Isabel M. , Muñoz Jaime A. , Rodríguez‐Navas Carmen , Alvarez Luis , Delgado‐Baeza Emilio , García‐Ruiz Josefa P. 
Published: January 2009

AbstractLiver regeneration after partial hepatectomy (PHx) is a complex process that is regulated by hemodynamic changes, the modulation of cytokines and growth factors, and the activation of immediate early transcription factors that lead to a round of hepatocyte mitosis. Among the factors involved, the pituitary hormone prolactin (PRL) has been shown to induce a hepatotrophic response after partial hepatectomy similar to that caused by phorbol esters; and in isolated hepatocytes PRL triggers a mitogenic response. However, it is becoming clear that PRL exerts a dual role acting in proliferation and differentiation processes. In this work, we have assessed the role of PRL in the early stages of liver regeneration in rats. To this end, three groups of rats were compared: Sham operated, regenerant and regenerant with PRL i.p. administration. Results show that PRL administration prior to partial hepatectomy caused an increase in the binding activity of several transcription factors involved in cell proliferation: AP‐1, c‐Jun and STAT‐3, and in liver‐specific differentiation and maintenance of energetic metabolism: CEBPα, HNF‐1, HNF‐4 at early time points and at later time points HNF‐3. Hepatic sections show that PRL administration increases the number of proliferating cells within 5 h post‐partial hepatectomy. The mRNA of the angiogenic and survival factors VEGF and HIF‐1α, was also induced by PRL treatment. Data indicate that PRL triggers, either directly or indirectly, an acceleration of liver regeneration, preserving liver function and fulfilling a hepatoprotective role. J. Cell. Physiol. 219: 626–633, 2009. © 2009 Wiley‐Liss, Inc.
Mitochondrial localization, ELK‐1 transcriptional regulation and growth inhibitory functions of BRCA1, BRCA1a, and BRCA1b proteins
Authors: Maniccia Anna W. , Lewis Catherine , Begum Nurjahan , Xu Jingyao , Cui Jianqi , Chipitsyna Galina , Aysola Kartik , Reddy Vaishali , Bhat Ganapathy , Fujimura Yasuo , Henderson Beric , Reddy E. Shyam P. , Rao Veena N. 
Published: January 2009

AbstractBRCA1 is a tumor suppressor gene that is mutated in families with breast and ovarian cancer. Several BRCA1 splice variants are found in different tissues, but their subcellular localization and functions are poorly understood at the moment. We previously described BRCA1 splice variant BRCA1a to induce apoptosis and function as a tumor suppressor of triple negative breast, ovarian and prostate cancers. In this study we have analyzed the function of BRCA1 isoforms (BRCA1a and BRCA1b) and compared them to the wild‐type BRCA1 protein using several criteria like studying expression in normal and tumor cells by RNase protection assays, subcellular localization/fractionation by immunofluorescence microscopy and Western blot analysis, transcription regulation of biological relevant proteins and growth suppression in breast cancer cells. We are demonstrating for the first time that ectopically expressed GFP‐tagged BRCA1, BRCA1a, and BRCA1b proteins are localized to the mitochondria, repress ELK‐1 transcriptional activity and possess antiproliferative activity on breast cancer cells. These results suggest that the exon 9, 10, and 11 sequences (aa 263–1365) which contain two nuclear localization signals, p53, Rb, c‐Myc, γ‐tubulin, Stat, Rad51, Rad50 binding domains, angiopoietin‐1 repression domain are not absolutely required for mitochondrial localization and growth suppressor function of these proteins. Since mitochondrial dysfunction is a hallmark of cancer, we can speculate that the mitochondrial localization of BRCA1 proteins may be functionally significant in regulating both the mitochondrial DNA damage as well as apoptotic activity of BRCA1 proteins and mislocalization causes cancer. J. Cell. Physiol. 219: 634–641, 2009. © 2009 Wiley‐Liss, Inc.
Critical role of the N‐terminal cyclic AMP‐binding domain of Epac2 in its subcellular localization and function
Authors: Niimura Manabu , Miki Takashi , Shibasaki Tadao , Fujimoto Wakako , Iwanaga Toshihiko , Seino Susumu 
Published: January 2009

AbstractcAMP is a well‐known regulator of exocytosis, and cAMP‐GEFII (Epac2) is involved in the potentiation of cAMP‐dependent, PKA‐independent regulated exocytosis in secretory cells. However, the mechanisms of its action are not fully understood. In the course of our study of Epac2 knockout mice, we identified a novel splicing variant of Epac2, which we designate Epac2B, while renaming the previously identified Epac2 Epac2A. Epac2B, which lacks the first cAMP‐binding domain A in the N‐terminus but has the second cAMP‐binding domain B of Epac2A, possesses GEF activity towards Rap1, as was found for Epac2A. Immunocytochemical analysis revealed that exogenously introduced Epac2A into insulin‐secreting MIN6 cells was localized near the plasma membrane, while Epac2B was found primarily in the cytoplasm. Interestingly, cAMP‐binding domain A alone introduced into MIN6 cells was also localized near the plasma membrane. In MIN6 cells, Epac2A was involved in triggering hormone secretion by stimulation with 5.6 mM glucose plus 1 mM 8‐Bromo‐cAMP, but Epac2B was not. The addition of a membrane‐targeting signal to the N‐terminus of Epac2B was able to mimic the effect of Epac2A on hormone secretion. Thus, the present study indicates that the N‐terminal cAMP‐binding domain A of Epac2A plays a critical role in determining its subcellular localization and potentiating insulin secretion by cAMP. J. Cell. Physiol. 219: 652–658, 2009. © 2009 Wiley‐Liss, Inc.
Hemin promotes proliferation and differentiation of endothelial progenitor cells via activation of AKT and ERK
Authors: Wang Jir‐You , Lee Yi‐Tsun , Chang Pi‐Fei , Chau Lee‐Young 
Published: January 2009

AbstractIncreased neovascularization is commonly observed in hemorrhagic plaques and associated with rupture of atherosclerotic lesions. This study aims to investigate whether hemin accumulated at the site of hematoma promotes neovascularization through affecting the growth and function of endothelial progenitor cells (EPCs) and the possible mechanism involved. Here we demonstrated that hemin promoted a significant increase in neovessel formation in matrigel plugs embedded in vivo and enhanced the proliferation and endothelial gene expression in EPCs in vitro. VEGF‐induced migration response and the capability to incorporate into the vascular networks were markedly enhanced in hemin‐treated EPCs. Hemin induced the phosphorylation of ERK and AKT but not p38 or JNK. The inhibition of AKT or ERK activation significantly attenuated the effect of hemin on cell proliferation. However, the enhanced migration response induced by hemin was significantly suppressed by the inhibition of AKT but not ERK. Hemin induced significant increase in reactive oxygen species (ROS) production and hemin‐induced angiogenic response of EPCs was substantially reduced by treatment with N‐acetylcysteine. Collectively, these data support that hemin‐induced ROS mediates the activation of AKT and ERK signaling pathways, which in turn promotes the cell proliferation and function of EPCs. J. Cell. Physiol. 219: 617–625, 2009. © 2009 Wiley‐Liss, Inc.
Chemoenzymatic synthesis: a strategy to obtain xylitol monoesters
Authors: Rufino Alessandra R. , Biaggio Francisco C. , Santos Júlio C. , de Castro Heizir F. 
Published: January 2009

AbstractBACKGROUND: Fatty acid sugar esters are used as non‐ionic surfactants in cosmetics, foodstuffs and pharmaceuticals. In particular, monoesters of xylitol have attracted industrial interest due to their outstanding biological activities. In this work, xylitol monoesters were obtained by chemoenzymatic synthesis, in which, first, xylitol was made soluble in organic solvent by chemo‐protecting reaction, followed by enzymatic esterification reaction using different acyl donors. A commercial immobilized Candida antartica lipase was used as catalyst, and reactions with pure xylitol were carried out to generate data for comparison.RESULTS: t‐BuOH was found to be the most suitable solvent to carry out esterification reactions with both pure and protected xylitol. The highest yields were obtained for reactions carried out with pure xylitol, but in this case by‐products, such as di‐ and tri‐esters isomers were formed, which required a multi‐step purification process. For the systems with protected xylitol, conversions of 86%, 58% and 24% were achieved using oleic, lauric and butyric acids, respectively. The structures of the monoesters were confirmed by 13C‐ and 1H‐NMR and microanalysis.CONCLUSION: The chemoenzymatic synthesis of xylitol monoesters avoided laborious downstream processing when compared with reactions performed with pure xylitol. Monoesters production from protected xylitol was shown to be a practical, economical, and clean route for this process, allowing a simple separation, because there are no other products formed besides xylitol monoesters and residual xylitol. Copyright © 2009 Society of Chemical Industry
Ozonation of complex industrial park wastewater: effects on the change of wastewater characteristics
Authors: Fanchiang Jen‐Mao , Tseng Dyi‐Hwa , Guo Gia‐Luen , Chen Hsi‐Jien 
Published: January 2009

AbstractBACKGROUND: Ozonation of complex industrial park wastewater was carried out in a semi‐batch reactor. The variation of wastewater characteristics was evaluated based on the analysis of 5‐day biochemical oxygen demand (BOD5) concentration, BOD5/chemical oxygen demand (COD) ratio, COD fractionation, and dissolved organic carbon (DOC) molecular size distribution before and after ozonation.RESULTS: The experimental results indicated that low efficiency of COD removal with increasing tendency of BOD5 concentration generally appeared after ozonation. Also, the BOD5/COD ratio increased from an initial of 0.27 to a maximum of 0.38. The COD fractionation tests revealed that most of the inert soluble COD was transformed to biodegradable soluble COD at 30 min of reaction time. Additionally, the DOC molecular size distribution tests showed that the fraction larger than 500 kDa was significantly decreased and the fraction smaller than 2 kDa was increased when the reaction time was prolonged to 240 min.CONCLUSION: This study verified that partial oxidation of the complex industrial park wastewater by ozonation could enhance wastewater biodegradability. The biodegradability enhancement was primarily because the inert soluble COD fraction was converted to the biodegradable soluble COD and the high molecular weight fraction of DOC was shifted toward the low molecular weight fraction. Copyright © 2009 Society of Chemical Industry
Glutathione peroxidase overexpression does not rescue impaired neurogenesis in the injured immature brain
Authors: Potts Matthew B. , Rola Radoslaw , Claus Catherine P. , Ferriero Donna M. , Fike John R. , Noble‐Haeusslein Linda J. 
Published: January 2009

AbstractTraumatic brain injury (TBI) is a leading cause of disability among young children and is associated with long‐term cognitive deficits. These clinical findings have prompted an investigation of the hippocampus in an experimental model of trauma to the developing brain at postnatal day (p21). Previous studies using this model have revealed a progressive loss of neurons in the hippocampus as brain‐injured animals mature to young adulthood. Here we determined whether this hippocampal vulnerability is likewise reflected in altered neurogenesis and whether the antioxidant glutathione peroxidase (GPx) modulates neurogenesis during maturation of the injured immature brain. Male transgenic mice that overexpress GPx and wild‐type littermates were subjected to controlled cortical impact or sham surgery on p21. At 2 weeks postinjury, the numbers of proliferating cells and immature neurons within the subgranular zone were measured by using Ki‐67 and doublecortin, respectively. Bromodeoxyuridine (BrdU) was used to label dividing cells beginning 2 weeks postinjury. Survival (BrdU+) and neuronal differentiation (BrdU+/NeuN+) were then measured 4 weeks later via confocal microscopy. Two‐way ANOVA revealed no significant interaction between genotype and injury. Subsequent analysis of the individual effects of injury and genotype, however, showed a significant reduction in subgranular zone proliferation (Ki‐67) at 2 weeks postinjury (P = 0.0003) and precursor cell survival (BrdU+) at 6 weeks postinjury (P = 0.016) and a trend toward reduced neuronal differentiation (BrdU+/NeuN+) at 6 weeks postinjury (P = 0.087). Overall, these data demonstrate that traumatic injury to the injured immature brain impairs neurogenesis during maturation and suggest that GPx cannot rescue this reduced neurogenesis. © 2009 Wiley‐Liss, Inc.