bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine release of mononuclear leukocytes (PBMC) after contact to a carbonated calcium phosphate bone cement
Authors: Schildhauer T.A. , Chapman J.R. , Muhr G. , Köller M. 
Published: April 2006

AbstractHuman leukocytes (peripheral blood mononuclear cells, PBMC) were overlaid on calcium phosphate bone cement (CBC, Norian SRS®) and allowed to settle for 1 h under cell culture conditions. Subsequently, the cells were either left unstimulated (i.e. sham stimulation using cell culture medium), or stimulated with toxic shock syndrome toxin‐1 (TSST‐1, 10 ng/mL), staphylococcal enterotoxin B (SEB, 10 ng/mL), or concanavalin A (ConA, 2 μg/mL) for further 24 h using cell culture conditions. Supernatants were then analyzed for cytokine content (interleukin‐1 receptor antagonist, IL‐1ra; IL‐2; IL‐6; IL‐10; IL‐12) by enzyme‐linked immunosorbent assay. While the spontaneous generation of cytokines was not influenced, the IL‐2 release from stimulated PBMC was significantly decreased in contrast to other analyzed cytokines after contact to the curing CBC compared to control incubations without CBC. This decrease in IL‐2 release was not due to known inhibitors of IL‐2 synthesis platelet factor‐4 (PF‐4), IL‐10, TGF‐β, or elevated calcium ion concentrations. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Modulation of amino acid uptake by TGF‐β in lung myofibroblasts
Authors: Subramanian Mangalalaxmy , Kuang Ping‐Ping , Wei Lin , Rishikof David C. , Liu Hanqiao , Goldstein Ronald H. 
Published: April 2006

AbstractHormones such as insulin, growth factors, and cell stress stimulate system A amino acid transporter. Transforming growth factor‐β (TGF‐β) stimulates amino acid uptake thereby inducing cell proliferation, cellular hypertrophy, and matrix synthesis. Insulin appears to activate amino acid in smooth muscle cells via a phosphatidylinositol 3‐kinase (PI3‐kinase)‐dependent pathway. We examine the effect and interaction of TGF‐β, insulin, and PI3‐kinase activity on amino acid uptake in human lung myofibroblasts. TGF‐β treatment induced large increases in system A activity and a small delayed increase in the phosphorylation of protein kinase B, also termed phospho‐Akt. In contrast, insulin induced small increases in system A activity and large increases in phospho‐Akt levels. LY294002, a PI3‐kinase inhibitor, blocked the TGF‐β‐induced amino acid uptake only partially, but completely blocked TGF‐β‐induced Akt phosphorylation. Moreover, the level of phospho‐Smad3 was found to be high even when LY294002 blocked TGF‐β‐induced phospho‐Akt levels. Inhibition of PI3‐kinase activity resulted in increase in Km, consistent with a major change in transporter activity without change in transporter number. The PI3‐kinase inhibitor also did not change the amino acid transporter 2 (ATA2) mRNA levels. Taken together, these results suggest that TGF‐β induced Smad‐3 and amino acid uptake through a PI3‐kinase independent pathway. © 2006 Wiley‐Liss, Inc.
Elevated serum kininogen in patients with paget's disease of bone: A role in marrow stromal/preosteoblast cell proliferation
Authors: Tsuruga Eichi , Rao D. Sudhaker , Baatz John E. , Reddy Sakamuri V. 
Published: April 2006

AbstractPaget's disease (PD) of bone is a chronic focal skeletal disorder characterized by excessive bone resorption followed by abundant new bone formation. Enhanced levels of IL‐6, RANKL, M‐CSF, and endothelin‐1 have been associated with PD. In the present study, we identified increased serum levels (2 to 5‐fold) of inflammatory cytokine, kininogen (KNG) in patients with PD compared to normal subjects. Treatment of pagetic bone marrow derived stromal/preosteoblast cells with recombinant KNG (25 ng/ml) for 24 h period resulted in a 5‐fold increase in the levels of phospho‐HSP27 and a 3‐fold increase in ERK1/2 phosphorylation in these cells. However, pagetic stromal cells stimulated with KNG in the presence of ERK activation inhibitor peptide did not significantly affect the levels of phospho‐HSP27. KNG increased normal and pagetic marrow stromal cell proliferation at 1.4‐fold and 2.5‐fold, respectively. KNG in the presence of an ERK inhibitor peptide did not stimulate pagetic marrow stromal cell proliferation. Furthermore, siRNA suppression of HSP27 expression significantly decreased KNG inhibition of etoposide‐induced caspase‐3 activation and apoptosis in these cells. In summary, KNG modulate bone marrow derived stromal/preosteoblast cell proliferation and suppress etoposide‐induced apoptosis through ERK and HSP27 activation, respectively. These results implicate a pathophysiologic role for KNG in patients with PD. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Nuclear addressing provides a clue for the transforming activity of amino‐truncated CCN3 proteins
Authors: Planque Nathalie , Long Li Chang , Saule Simon , Bleau Anne‐Marie , Perbal Bernard 
Published: April 2006

AbstractCCN3 is a founding member of the CCN (Cyr61, Ctgf, Nov) family of cell growth and differentiation regulators. These secreted proteins are key regulators in embryonic development, and are associated with severe pathologies including fibrotic diseases and cancers. CCN3 was discovered as a MAV integration site in an avian nephroblastoma. Previous work established that the amino‐truncated protein expressed in this tumor was inducing morphological transformation of chicken embryo fibroblasts, whereas the full‐length secreted CCN3 protein was inhibiting cell growth. Amino‐truncated variants were identified in cancer cell lines. Since the lack of signal peptide was expected to alter the fate of the truncated proteins, we hypothesized that modifications of CCN3 subcellular addressing could be responsible for the oncogenic activities of CCN3. The CCN proteins are composed of four structural modules (IGFBP, TSP1, VWC, and CT). We report that amino‐truncated variants of CCN3 are addressed to the nucleus and that the carboxyterminal (CT) module of CCN3 is responsible for the nuclear addressing. Furthermore, our data identify nuclear CCN3 variants as potential transcriptional regulators. In this context, the CT module confers on nuclear CCN3 proteins a negative regulatory effect on transcription. We propose that the nuclear localization of amino‐truncated CCN3 proteins be correlated to oncogenicity. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways
Authors: Shinoda Yusuke , Yamaguchi Masayuki , Ogata Naoshi , Akune Toru , Kubota Naoto , Yamauchi Toshimasa , Terauchi Yasuo , Kadowaki Takashi , Takeuchi Yasuhiro , Fukumoto Seiji , Ikeda Toshiyuki , Hoshi Kazuto , Chung Ung‐il , Nakamura Kozo , Kawaguchi Hiroshi 
Published: April 2006

AbstractSince interaction between bone and lipid metabolism has been suggested, this study investigated the regulation of bone metabolism by adiponectin, a representative adipokine, by analyzing deficient and overexpressing transgenic mice. We initially confirmed that adiponectin and its receptors were expressed in osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone not only through an endocrine pathway as a hormone secreted from fat tissue, but also through an autocrine/paracrine pathway. There was no abnormality in bone mass or turnover of adiponectin‐deficient (Ad−/−) mice, possibly due to an equivalent balance of the two pathways. In the culture of bone marrow cells from the Ad−/− mice, osteogenesis was decreased compared to the wild‐type (WT) cell culture, indicating a positive effect of endogenous adiponectin through the autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we analyzed transgenic mice overexpressing adiponectin in the liver, and found no abnormality in the bone. Addition of recombinant adiponectin in cultured osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action of circulating adiponectin was negative for bone formation. In the presence of insulin, however, this suppression was blunted, and adiponectin enhanced the insulin‐induced phosphorylations of the main downstream molecule insulin receptor substrate‐1 and Akt. These lines of results suggest three distinct adiponectin actions on bone formation: a positive action through the autocrine/paracrine pathway by locally produced adiponectin, a negative action through the direct pathway by circulating adiponectin, and a positive action through the indirect pathway by circulating adiponectin via enhancement of the insulin signaling. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Modulation by the steroid/thyroid hormone superfamily of TGF‐β‐stimulated VEGF release from vascular smooth muscle cells
Authors: Tanabe Kumiko , Tokuda Haruhiko , Takai Shinji , Matsushima‐Nishiwaki Rie , Hanai Yoshiteru , Hirade Kouseki , Katagiri Yoshihiro , Dohi Shuji , Kozawa Osamu 
Published: April 2006

AbstractWe previously reported that transforming growth factor‐β (TGF‐β) stimulates the release of vascular endothelial growth factor (VEGF) from aortic smooth muscle A10 cells via activation of p38 mitogen‐activated protein (MAP) kinase. In the present study, we investigated whether nuclear hormone receptor superfamily members affect TGF‐β‐stimulated VEGF release from A10 cells. Retinoic acid or 1,25‐dihydroxyvitamin D3 enhanced TGF‐β‐induced VEGF release in a concentration‐dependent manner, whereas dexamethasone or corticosterone suppressed TGF‐β‐induced VEGF release. 1,25‐Dihydroxyvitamin D3 and TGF‐β stimulated phosphorylation of p38 MAP kinase in an additive manner. SB203580, an inhibitor of p38 MAP kinase, decreased the VEGF release induced by TGF‐β or 1,25‐dihydroxyvitamin D3. However, retinoic acid, dexamethasone, or corticosterone did not affect phosphorylation of p38 MAP kinase. These results indicate that retinoic acid, 1,25‐dihydroxyvitamin D3, and glucocorticoids affect TGF‐β‐stimulated VEGF release from aortic smooth muscle cells. The stimulatory effect of 1,25‐dihydroxyvitamin D3 occurs, in part, via modification of TGF‐β‐induced activation of p38 MAP kinase. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
CREB‐dependent cyclooxygenase‐2 and microsomal prostaglandin E synthase‐1 expression is mediated by protein kinase C and calcium
Authors: Pham Hung , Shafer Lindsay M. , Slice Lee W. 
Published: April 2006

AbstractCellular production of prostaglandins (PGs) is controlled by the concerted actions of cyclooxygenases (COX) and terminal PG synthases on arachidonic acid in response to agonist stimulation. Recently, we showed in an ileal epithelial cell line (IEC‐18), angiotensin II‐induced COX‐2‐dependent PGI2 production through p38MAPK, and calcium mobilization (J. Biol. Chem. 280: 1582–1593, 2005). Agonist binding to the AT1 receptor results in activation of PKC activity and Ca2+ signaling but it is unclear how each pathway contributes to PG production. IEC‐18 cells were stimulated with either phorbol‐12,13‐dibutyrate (PDB), thapsigargin (TG), or in combination. The PG production and COX‐2 and PG synthase expression were measured. Surprisingly, PDB and TG produced PGE2 but not PGI2. This corresponded to induction of COX‐2 and mPGES‐1 mRNA and protein. PGIS mRNA and protein levels did not change. Activation of PKC by PDB resulted in the activation of ERK1/2, JNK, and CREB whereas activation of Ca2+ signaling by TG resulted in the delayed activation of ERK1/2. The combined effect of PKC and Ca2+ signaling were prolonged COX‐2 and mPGES‐1 mRNA and protein expression. Inhibition of PKC activity, MEK activity, or Ca2+ signaling blocked agonist induction of COX‐2 and mPGES‐1. Expression of a dominant negative CREB (S133A) blocked PDB/TG‐dependent induction of both COX‐2 and mPGES‐1 promoters. Decreased CREB expression by siRNA blocked PDB/TG‐dependent expression of COX‐2 and mPGES‐1 mRNA. These findings demonstrate a coordinated induction of COX‐2 and mPGES‐1 by PDB/TG that proceeds through PKC/ERK and Ca2+ signaling cascades, resulting in increased PGE2 production. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Nuclease sensitive element binding protein 1 gene disruption results in early embryonic lethality
Authors: Fan Lin , Jones Stephen N. , Padden Carolyn , Shen Qichang , Newburger Peter E. 
Published: April 2006

AbstractNuclease sensitive element binding protein 1 (NSEP1) is a member of the EFIA/NSEP1/YB‐1 family of DNA‐binding proteins whose members share a cold shock domain; it has also been termed DNA‐binding protein B and Y box binding protein‐1 because of its recognition of transcriptional regulatory elements. In addition, NSEP1 functions in the translational regulation of renin, ferritin, and interleukin 2 transcripts, and our laboratory has reported that it plays a role in the biosynthesis of selenium‐containing proteins. To test the functional importance of NSEP1 in murine embryonic development, we have utilized a clone of ES cells in which the NSEP1 gene had been disrupted by integration of a plasmid gene‐trapping vector into the seventh exon. Injection of these cells into C57BL/6 blastocysts resulted in 11 high percentage chimeric mice; crosses to wild type C57BL/6 mice generated 82 F1 agouti mice, indicating germ line transmission of the ES cell clone, but genotyping showed no evidence of the disrupted allele in any of these agouti offspring even though spermatozoa from four of five tested mice contained the targeted allele. Embryos harvested after timed matings of chimeric male mice demonstrated only the wildtype allele in 27 embryos tested at E7.5, E12.5, and E18.5. These results suggest that gene targeting of NSEP1 induces a lethal phenotype in early embryos, due to either haploinsufficiency of NSEP1 or formation of a dominant negative form of the protein. In either case, these data indicate the functional importance of the NSEP1 gene in murine early embryonic development. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Diabetes modulates differentially creatine kinase‐specific activity responsiveness to estradiol‐17β and to raloxifene in rat organs
Authors: Somjen Dalia , Shen Michal , Stern Naftali , Mirsky Nitsa 
Published: April 2006

AbstractDiabetes mellitus increases the risk for CVD in women. While there is considerable evidence suggesting beneficial effects of estrogen on decreasing lipid peroxidation, atherosclerotic processes, and cardiovascular diseases, diabetes negates most estrogen protective effects as well as the skeletal protective effects of estrogens, which are not discernable in diabetic women. In the present study, we examined the in vivo effects of estradiol‐17β (E2), on creatine kinase (CK)‐specific activity, in estrogen‐responsive organs from healthy and diabetic rats. Healthy or diabetic (streptozotocin‐induced) female rats were injected with either E2 (10–50 µg/rat) or raloxifene (Ral; 500–1,000 µg/rat). Twenty‐four hours following the injection, animals were sacrificed; their organs removed and assayed for CK‐specific activity. CK‐specific activity in different organs [Left ventricle of heart (Lv), uterus (Ut), aorta (Ao), para uterine adipose tissue (Ad), epiphyseal cartilage (Ep), and diaphyseal bone (Di)] from healthy animals, was stimulated with increased doses of E2, with maximum at 20 µg/rat. Age‐matched diabetic female rats exhibited a remarkable decreased response to E2 in all organs except Ut. In contrast, the response to Ral was not altered in diabetic rats. Similar results were observed in organs from ovariectomized female rats (Ovx), healthy or diabetic. These results support our previous in vitro findings, demonstrating that hyperglycemia decreases CK response to E2 but not to Ral in cultured human vascular and bone cells. In summary, diabetes mellitus decreases CK response to E2 but not that of Ral in skeletal and vascular tissues. The decreased response to E2 detected in organs derived from diabetic rats might be due to changes in nuclear and/or membrane estrogen receptors and/or other genomic and non‐genomic pathways, as was shown in in vitro cellular models. J. Cell. Biochem. 99: 133–139, 2006. © 2006 Wiley‐Liss, Inc.
Downregulation of the RECK‐tumor and metastasis suppressor gene in glioma invasiveness
Authors: Corrẽa Tatiana C. Silveira , Brohem Carla Abdo , Winnischofer Sheila Maria Brochado , da Silva Cardeal Laura Beatriz , Sasahara Regina Maki , Taboga Sebastião Roberto , Sogayar Mari Cleide , Maria‐Engler Silvya Stuchi 
Published: April 2006

AbstractInvasive behavior is the pathological hallmark of malignant gliomas, being responsible for the failure of surgery, radiation, and chemotherapy. Matrix metalloproteinases (MMPs) are essential for proper ECM remodeling and invasion. The tumor and metastasis suppressor RECK protein regulates at least three members of the MMPs family: MMP‐2, MMP‐9, and MT1‐MMP. In order to mimic the in vivo invasion process, A172 and T98G, respectively, non‐invasive and invasive human glioblastoma cell lines, were cultured onto uncoated (control) or type I collagen gel‐coated surface, and maintained for up to 7 days to allow establishment of the invasive process. We show that the collagen substrate causes decreased growth rates and morphological alterations correlated with the invasive phenotype. Electronic transmission microscopy of T98G cells revealed membrane invaginations resembling podosomes, which are typically found in cells in the process of crossing tissue boundaries, since they constitute sites of ECM degradation. Real time PCR revealed higher RECK mRNA expression in A172 cells, when compared to T98G cells and, also, in samples obtained from cultures where the invasive process was fully established. Interestingly, the collagen substrate increases RECK expression in A172 cells and the same tendency is displayed by T98G cells. MMPs‐2 and ‐9 displayed higher levels of expression and activity in T98G cells, and their activities are also upregulated by collagen. Therefore, we suggest that: (1) RECK downregulation is critical for the invasiveness process displayed by T98G cells; (2) type 1 collagen could be employed to modulate RECK expression in glioblastoma cell lines. Since a positive correlation between RECK expression and patients survival has been noted in several types of tumors, our results may contribute to elucidate the complex mechanisms of malignant gliomas invasiveness. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells
Authors: Messner Donald J. , Romeo Charles , Boynton Alton , Rossie Sandra 
Published: April 2006

AbstractThe microbial toxin okadaic acid (OA) specifically inhibits PPP‐type ser/thr protein phosphatases. OA is an established tumor promoter with numerous cellular effects that include p53‐mediated cell cycle arrest. In T51B rat liver epithelial cells, a model useful for tumor promotion studies, p53 activation is induced by tumor‐promoting (low nanomolar) concentrations of OA. Two phosphatases sensitive to these concentrations of OA, PP2A and protein phosphatase 5 (PP5), have been implicated as negative regulators of p53. In this study we examined the respective roles of these phosphatases in p53 activation in non‐neoplastic T51B cells. Increases in p53 activity were deduced from levels of p21 (cip1) and/or the rat orthologue of mdm2, two p53‐regulated gene products whose induction was blocked by siRNA‐mediated knockdown of p53. As observed with 10 nM OA, both phospho‐ser15‐p53 levels and p53 activity were increased by 10 µM fostriecin or SV40 small t‐antigen. Both of these treatments selectively inhibit PP2A but not PP5. siRNA‐mediated knockdown of PP2A, but not PP5, also increased p53 activity. Finally, adenoviral‐mediated over‐expression of an OA‐resistant form of PP5 did not prevent increased phospho‐ser15‐p53, p53 protein, or p53 activity caused by 10 nM OA. Together these results indicate that PP5 blockade is not responsible for OA‐induced p53 activation and G1 arrest in T51B cells. In contrast, specific blockade of PP2A mimics p53‐related responses to OA in T51B cells, suggesting that PP2A is the target for this response to OA. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non‐diabetic rats
Authors: Cho William C. , Yip Tai‐Tung , Chung Wai‐Shing , Leung Albert W. , Cheng Christopher H. , Yue Kevin K. 
Published: April 2006

AbstractDiabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C‐reactive protein (CRP) in the Swiss‐Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Post‐translational modification by O‐GlcNAc: Another way to change protein function
Authors: Kudlow Jeffrey E. 
Published: April 2006

AbstractModification of intracellular proteins by the β‐linkage of the monosaccharide, N‐acetylglucosamine to serine or threonine hydroxyls (O‐GlcNAc) is abundant and reversible. Although many proteins bear this post‐translational covalent modification, the changes in function of the proteins as a result of this modification are only starting to be understood. In this article, we describe how aspects of the flux from the glucose backbone to this modification are modified and how the cellular activity and content of the GC‐box binding transcription factor, Sp1, is altered by O‐glycosylation. The association of the enzyme that puts on the O‐GlcNAc modification with the bi‐functional enzyme that removes this modification is discussed relative to the transition between transcriptional repression and activation. J. Cell. Biochem. 98: 1062–1075, 2006. © 2006 Wiley‐Liss, Inc.
Pro‐metastasis function of TGFβ mediated by the smad pathway
Authors: Kang Yibin 
Published: April 2006

AbstractThe transforming growth factor beta (TGFβ) signaling pathway plays a vital role in the development and homeostasis of normal tissues. Abnormal function of this pathway contributes to the initiation and progression of cancer. Smad proteins are key signal transducers of the TGFβ pathway and are essential for the growth suppression function of TGFβ. Smads are bona fide tumor suppressors whose mutation, deletion, and silencing are associated with many types of human cancer. However, the involvement and functional mechanism of Smad proteins in cancer metastasis are poorly defined. Recent studies using genetically modified cancer cells and mouse tumor models have provided concrete evidence for a Smad‐dependent mechanism for metastasis promotion by TGFβ. Understanding the dual roles of Smad proteins in tumor initiation and progression has important implications for cancer therapeutics. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.