factor-1 igf-1 igf-binding: Topics by WorldWideScience.org

Inhibitory effect of transforming growth factor-#beta# (TGF-#beta#) on insulin-like growth factor 1 (IGF-1)-induced proliferation and differentiation in primary cultures of pig preadipocytes

The influence of serum, IGF-1 and TGF-{beta} on the differentiation of preadipocytes was examined in primary cultures of porcine adipose tissue cells. In serum-supplemented or serum-free, IGF-1 (1 and 10 nM) had no effect on total cell number. However, IGF-1 (10nM) increased adipocyte number only in serum-supplemented (1% pig serum) cultures, whereas TGF-{beta} (15 pm) reduced the adipocyte number in the presence and absence of IGF-1. Replication of preadipocytes was analyzed with a ({sup 3}H) thymidine assay. Preadipocyte proliferation (cpm in adipocyte fraction) was increased by IGF-1 (10nM) only in cultures containing pig serum. TGF-{beta} had no effect on preadipocyte proliferation specifically, but slightly increased total ({sup 3}H) thymidine incorporation in cultures with ...

1990-02-26

Effects of Short-Term Treadmill Exercise Training or Growth Hormone Supplementation on Diastolic Function and Exercise Tolerance in Old Rats

The influence of serum, IGF-1 and TGF-#beta# on the differentiation of preadipocytes was examined in primary cultures of porcine adipose tissue cells. In serum-supplemented or serum-free, IGF-1 (1 and 10 nM) had no effect on total cell number. However, IGF-1 (10nM) increased adipocyte number only in serum-supplemented (1% pig serum) cultures, whereas TGF-#beta# (15 pm) reduced the adipocyte number in the presence and absence of IGF-1. Replication of preadipocytes was analyzed with a ["3H] thymidine assay. Preadipocyte proliferation (cpm in adipocyte fraction) was increased by IGF-1 (10nM) only in cultures containing pig serum. TGF-#beta# had no effect on preadipocyte proliferation specifically, but slightly increased total ["3H] thymidine incorporation in cultures with serum. ...

1991-04-21

Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor

Whether the lusitropic potential of short-term exercise in aged rats is linked to an augmentation in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and an alteration in the...Full Text Available

2008-09-01

The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing

Mammals possess multiple insulin-like growth factor (IGF) binding proteins (IGFBPs), and related proteins, that modulate the activity of insulin/IGF signalling (IIS), a conserved neuroendocrine signalling...Full Text Available

2011-02-01

PDP-1 Links the TGF-? and IIS Pathways to Regulate Longevity, Development, and Metabolism

Inhibiting insulin/IGF-1 signalling extends lifespan and delays age-related disease in species throughout the animal kingdom. This life-extension pathway, the first to be defined, was discovered through...Full Text Available

2011-01-12

Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes

The insulin/IGF-1 signaling (IIS) pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1...Full Text Available

2011-04-01

Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden Longevity Study

To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% fetal bovine serum, ...

1985-01-01

Opposing function of mitochondrial prohibitin in aging

Human longevity is in part genetically determined, and the insulin/IGF-1 signal transduction (IIS) pathway has consistently been implicated. In humans, type 2 diabetes is a frequent disease that results...Full Text Available

Number of aberrant crypt foci associated with adiposity and IGF1 bioavailability

While specific signalling cascades involved in aging, such as the insulin/IGF-1 pathway, are well-described, the actual metabolic changes they elicit to prolong lifespan remain obscure. Nevertheless,...Full Text Available

If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice

BackgroundDysregulation of the insulin-like growth factor (IGF) system, a common consequence of adiposity-induced insulin resistance, may be a key underlying mechanism...Full Text Available

2009-07-01

Evidence for an association between TSH and IGF-1 receptors

Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer...Full Text Available

Manganese Induces IGF-1 and Cyclooxygenase-2 Gene Expressions in the Basal Hypothalamus during Prepubertal Female Development

TSH receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs in Graves’ disease (GD-IgG). Whether TSHR is involved in the pathogenesis of thyroid associated...Full Text Available

2008-09-15

British Library Electronic Table of Contents (United Kingdom)

Precocious puberty is a significant child health problem, especially in girls, because 95% of cases are idiopathic. Our earlier studies demonstrated that low-dose levels of manganese (Mn) caused precocious puberty via stimulating the secretion of luteinizing hormone-releasing hormone (LHRH). Because glial-neuronal communications are important for the activation of LHRH secretion at puberty, we investigated the effects of prepubertal Mn exposure on specific glial-derived puberty-related genes known to affect neuronal LHRH release. Animals were supplemented with MnCl2 (10 mg/kg) or saline by gastric gavage from day 12 until day 22 or day 29, then decapitated, and brains removed. The site of LHRH release is the medial basal hypothalamus (MBH), and tissues from this area were analyzed by real-...

2011-01-01

Cloning and mapping of the mouse {alpha}7-neuronal nicotinic acetylcholine receptor

The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects

We report the isolation of cDNA clones for the mouse {alpha}7 neuronal nicotinic acetylcholine receptor subunit (gene symbol Acra7), the only nicotinic receptor subunit known to bind a-bungarotoxin in mammalian brain. This gene may have relevance to nicotine sensitivity and to some electrophysiologic findings in schizophrenia. The mouse {alpha}7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences. The {alpha}7 gene was mapped to mouse chromosome 7 near the p locus with the following gene order from proximal to distal: Myod1-3.5 {+-}1.7 cM-Gas2-0.9 cM {+-} 0.9 cM-D7Mit70-1.8 {+-} 1.2 cM- Acra7-4.4 {+-}1.0 cM-Hras1-ps11/Igf1r/Snrp2a. The human gene was confirmed to map to the homologous region of human chromosome 15q13-q14. 26 refs., 3 figs.

1995-03-20

Induced Expression of Doublesex-and mab-3-related Transcription Factor-1 (DMRT-1) mRNA by Testosterone in the Olive Flounder, Paralichthys olivaceus ovary

Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization....Full Text Available

2009-04-01

KoreaScience (Korea)

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2007-08-01

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice

A heteromeric complex containing the centromere binding factor 1 and two basic leucine zipper factors, Met4 and Met28, mediates the transcription activation of yeast sulfur metabolism.

Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover,...Full Text Available

2011-07-21

Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis

Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing...Full Text Available

1996-05-15

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Transforming growth factor-?1 induces intestinal myofibroblast differentiation and modulates their migration

Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one...Full Text Available

2010-11-01

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

AIM: To investigate the effects of transforming growth factor β1 (TGF-β1) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro.METHODS:...Full Text Available

2009-03-28

SirT3 suppresses hypoxia inducible factor 1? and tumor growth by inhibiting mitochondrial ROS production

Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects...Full Text Available

2006-09-13

Regulation of life span by mitochondrial respiration: the HIF-1 and ROS connection

It has become increasing clear that alterations in cellular metabolism have a key role in the generation and maintenance of cancer. Some of the metabolic changes can be attributed to the activation...Full Text Available

2011-06-30

Critical role of SDF-1?-induced progenitor cell recruitment and macrophage VEGF production in the experimental corneal neovascularization

A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for...Full Text Available

Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1? Have an Antagonistic Connection

PurposeTo address the roles of the stromal derived factor-1 (SDF-1) α in the course of experimental corneal neovascularization (CNV).MethodsCNV...Full Text Available

NADPH oxidase-mediated reactive oxygen species production activates hypoxia-inducible factor-1 (HIF-1) via the ERK pathway after hyperthermia treatment

The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines...Full Text Available

2010-11-01

Mutations at the accommodation gate of the ribosome impair RF2-dependent translation termination

Hyperthermia (HT) is a strong adjuvant treatment with radiotherapy and chemotherapy because it causes tumor reoxygenation. However, the detailed molecular mechanisms of how HT enhances tumor oxygenation...Full Text Available

2010-11-23

Changes of hypoxia inducible factor-1 ? in hepatoma cells irradiated by gamma ray and their mechanism

During protein synthesis, aminoacyl-tRNA (aa-tRNA) and release factors 1 and 2 (RF1 and RF2) have to bind at the catalytic center of the ribosome on the 50S subunit where they take part in peptide bond...Full Text Available

2010-09-01

Regulation of Redd1 Expression by Hypoxia

This paper reports regulation of hypoxia inducible factor-1 ? (HIF-1 ?)in hepatoma cells by irradiation. Cobalt chloride (CoCl2), a chemical mimic agent for hypoxia research, was utilized to induce the stable expression of HIF-1 ? in HepG2 cells. The HepG2 cells were irradiated to different doses to observe the changes of HIF-1 ?. The level of intracellular reactive oxygen species (ROS) was assayed by fluorescent microscope and flow cytometry (FCM). The results showed that there were obvious changes in expression of HIF-1 ? after HepG2 cells exposed to radiation, and the changes were positively related with the irradiation dose from 1 Gy to 5 Gy. Moreover, contents of incellular ROS were negatively correlated with above levels of HIF-1 ? from 1 Gy to 3 Gy. The results indicate that irradiation may enhance hypoxic cells HIF-1 ?, and the reduction of intracellular ROS can contribute to the regulation of ionizing radiation on HIF-1 ?. (authors)

2007-10-01

Displacement ventilation in industry - a design principle for improved air quality

Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.

2006-05-25

Regional assessment of ambient volatile organic compounds from biopharmaceutical R&D complex

There is very little quantitative documentation of actual improvements resulting from the installation of new general ventilation systems in industrial settings. Therefore the performance of the common mixing design principle was compared to the displacement design principle by means of an intervention study in a workshop (V = 12,000 m[sup 3]), where thermoplastics were moulded. An experimental signal-response tracer gas technique was used. In terms of supplying fresh air to the zone of occupancy the displacement system was better than the mixing system by a factor of 2. In terms of the exposure level to a simulated contaminant (tracer gas) the displacement system was better by a factor 1.5-18. (author)

1992-10-01

British Library Electronic Table of Contents (United Kingdom)

Biopharmaceutical R&D complexes are major emission sources of volatile organic compounds (VOCs), which may pose potential health risks for staff on site and residents nearby. In this paper health risk assessments were performed for the VOCs in the ambient air of a typical biopharmaceutical R&D complex in China. Results showed halogenated and alkyl compounds were dominant components among 24 major VOCs from 9 selected sampling sites, inside or around the complex. The principal component analysis (PCA) indicated VOCs were generated predominantly from the biopharmaceutical research activities (factor 1 (F1), 71.6%) and traffic vehicles (factor 2 (F2), 15.4%), which were confirmed by contour maps of five selected VOCs (benzene, toluene, chlorobenzene, methylene chloride and n-hexane) simulated...

2011-01-01

Study on the effectiveness of some decontamination agents against skin contamination of {sup 137}Cs and {sup 60}Co

Study on the effectiveness of some decontamination agents against skin contamination of "1"3"7Cs and "6"0Co

In order to evaluate the effectiveness of some decontamination agents against skin contamination of {sup 60}Co and {sup 137}Cs, the experiments were carried out in this study. In the experiments, pig skin was used instead of human skin, {sup 60}CoCl{sub 2} and {sup 137}CsCl were used the liquid sources of skin contamination. To examine the effectiveness of decontamination agents, skin decontamination was tried using soup, EDTA, DAERICON which was developed for decontamination of radionuclides on the surface of building structure, and new decontamination agents such as IOCON, TRICON, and CHARCON, which were developed in this study. The absorption of radionuclides through the skin was evaluated by the gamma-ray detection on the surface of sample skin after radionuclides were penetrated into the skin during 16 hour soiling time. The results of this absorption experiment indicated that 11.5% and 3.2% of initial amounts of {sup 137}Cs and {sup 60}Co, respectively, were penetrated into the ...

1998-03-01

Ultrashort echo time MRI of cortical bone at 7 tesla field strength: A feasibility study

In order to evaluate the effectiveness of some decontamination agents against skin contamination of "6"0Co and "1"3"7Cs, the experiments were carried out in this study. In the experiments, pig skin was used instead of human skin, "6"0CoCl_2 and "1"3"7CsCl were used the liquid sources of skin contamination. To examine the effectiveness of decontamination agents, skin decontamination was tried using soup, EDTA, DAERICON which was developed for decontamination of radionuclides on the surface of building structure, and new decontamination agents such as IOCON, TRICON, and CHARCON, which were developed in this study. The absorption of radionuclides through the skin was evaluated by the gamma-ray detection on the surface of sample skin after radionuclides were penetrated into the skin during 16 hour soiling time. The results of this absorption experiment indicated that 11.5% and 3.2% of initial amounts of "1"3"7Cs and "6"0Co, respectively, were penetrated into the skin. In the experiment to ...

1998-03-01

British Library Electronic Table of Contents (United Kingdom)

AbstractPurpose: To implement and examine the feasibility of a three-dimensional (3D) ultrashort TE (UTE) sequence on a 7 Tesla (T) clinical MR scanner in comparison with 3T MRI at high isotropic resolution. Materials and Methods: Using an in-house built saddle coil at both field strengths we have imaged mid-diaphysial sections of five fresh cadaveric specimens of the distal tibia. An additional in vivo scan was performed at 7 Tesla using a quadrature knee coil. Results: Using the same type of saddle coil at both field strengths, a significant increase in SNR at 7T compared with 3T (factor 1.7) was found. Significantly shorter T2* values were found at the higher field strength (T2* = 552.2 126 s at 7T versus T2* = 1163 391 s at 3T). Conclusion: UHF MRI at 7T has great potential for imaging...

2011-01-01

Study of Bs-> \\phi l^+ l^-$ Decay in a Single Universal Extra Dimension

CERN Document Server

Utilizing form factors calculated within the light-cone sum rules, we have evaluated the decay branching ratios of $B_s\\to \\phi\\gamma$ and $B_s\\to \\phi \\ell^+\\ell^-$ in a single universal extra dimension model (UED), which is viewed as one of the alternative theories beyond the standard model (SM). For the decay $B_s \\to \\phi \\ell^+\\ell^-$, the dilepton invariant mass spectra, the forward-backward asymmetry, and double lepton polarization are also calculated. For each case, we compared the obtained results with predictions of the SM. In lower values of the compactification factor 1/R, the only parameter in this model, we see the considerable discrepancy between the UED and SM models. However, when 1/R increases, the results of UED tend to diminish and at $1/R = 1000 \\mathrm{GeV}$, two models have approximately the same predictions. Compared with data from CDF of $B_s \\to \\phi \\mu^+ \\mu^-$, the 1/R tends to be larger than $350 ...

2011-01-01

Modified 9Cr-1Mo steel shows excellent potential for steam generator applications

HSP70, the earliest-induced gene in the zebrafish retina during optic nerve regeneration: Its role in cell survival

A 9Cr-1Mo steel with properties improved over other ferritics in the ranges from 9 to 12% Cr and 1 to 2% Mo and over the widely used 2 1/2 Cr-1Mo steel has recently been developed. The main changes in the modified alloy, compared with the standard alloy, include: addition of niobium and vanadium, to improve the alloy's elevated-temperature strength properties; a specified range for each element; and a specification for nitrogen, which is not listed for the standard 9Cr-1Mo. Microstructural work has indicated that the improved strength of the modified alloy comes from two factors: (1) fine M/sub 23/C/sub 6/ precipitate particles nucleate on Nb/C, N, which comes out first during the heat treatment; and (2) the vanadium enters M/sub 23/C/sub 6/ and retards its growth at the service temperature. Mechanical properties discussed were Charpy-impact, tensile, and creep properties. Other properties included were: thermal expansion coefficient, ...

1982-12-01

British Library Electronic Table of Contents (United Kingdom)

Fish retinal ganglion cells (RGCs) can survive and regrow their axons after optic nerve injury. Injured RGCs express anti-apoptotic proteins, such as Bcl-2, after nerve injury; however, upstream effectors of this anti-apoptotic protein are not yet fully understood. Heat shock proteins (HSPs) play a crucial role in cell survival against various stress conditions. In this study, we focused on HSP70 expression in the zebrafish retina after optic nerve injury. HSP70 mRNA and protein levels increased rapidly 2.3-fold in RGCs by 1-6 h after injury and returned to control levels by 1-3 days. HSP70 transcription is regulated by heat shock factor 1 (HSF1). HSF1 mRNA and phosphorylated-HSF1 protein rapidly increased by 2.2-fold in RGCs 0.5-6 h after injury. Intraocular injection of HSP inhibitor I s...

2011-01-01

Gap-junctional communication of bone marrow stromal cells is resistant to irradiation in vitro

Gap-junctional communication of bone marrow stromal cells is resistant to irradiation in vitro

Bone marrow is one of the most radiosensitive organs. Irradiation causes a marked decrease in the total number of hematopoietic cells in the bone marrow. The reticular meshwork structure of marrow stromal cells, however, is relatively resistant to irradiation. Unimpaired stromal cell structure has been thought to be a prerequisite for the repopulation of hematopoietic cells during recovery from the effects of irradiation. The reticular framework is maintained by cell adhesion apparatuses such as gap junctions. The in vitro radiobiologic survival values of a cloned stromal cell line, H-1/A, were studied (n = 1.8, D0 = 138 cGy). Radiation doses of up to 4000 cGy had no detectable effects on the production of colony-stimulating factor 1. H-1/A cells communicate with each other via gap junctions as determined by the sensitive dye-transfer method. Gap-junctional communication between H-1/A cells was resistant to different levels of irradiation (500 ...

1990-10-01

1 2 3

Electron spin resonance investigation of Mn^{2+} ions and their dynamics in manganese doped SrTiO_3

CERN Document Server

Using electron spin resonance, lattice position and dynamic properties of Mn2+ ions were studied in 0.5 and 2 % manganese doped SrTiO3 ceramics prepared by conventional mixed oxide method. The measurements showed that Mn2+ ions substitute preferably up to 97 % for Sr if the ceramics is prepared with a deficit of Sr ions. Motional narrowing of the Mn2+ ESR spectrum was observed when temperature increases from 120 K to 240-250 K that was explained as a manifestation of off-center position of this ion at the Sr site. From the analysis of the ESR spectra the activation energy Ea = 86 mV and frequency factor 1/?0 ? (2-10)x10^(-14) 1/s for jumping of the impurity between symmetrical off-center positions were determined. Both values are in agreement with those derived previously from dielectric relaxation. This proves the origin of dielectric anomalies in SrTiO3:Mn as those produced by the reorientation dynamics of Mn2+ dipoles.

2007-01-01

Angiogenic cytokines and growth factors in systemic sclerosis.

Science.gov (United States)

Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin 1 (Ang-1), stromal cell-derived factor 1 (SDF-1/CXCL12), endothelin-1 (ET-1), monocyte chemoattractant ...

2011-04-28

A DC-81-indole conjugate agent suppresses melanoma A375 cell migration partially via interrupting VEGF production and stromal cell-derived factor-1a-mediated signaling

British Library Electronic Table of Contents (United Kingdom)

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, a...

2011-01-01

Structural Insights into the Interaction of the Evolutionarily Conserved ZPR1 Domain Tandem with Eukaryotic EF1A, Receptors, and SMN Complexes

Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening.

Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and ...

2007-01-01

Science.gov (United States)

The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as potent submicromolar ...

2008-03-11

Olfactomedin 4 suppresses prostate cancer cell growth and metastasis via negative interaction with cathepsin D and SDF-1.

Science.gov (United States)

The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through regulating cell autophagy by ...

2011-04-05

Beta-delayed proton emission: a new series of precursors, and the measurement of 10"-"1"6 s nuclear lifetimes