26 results on '"Ben-Dror, I."'
Search Results
2. Doxorubicin and a butyric acid derivative effectively reduce levels of BCL-2 protein in the cells of chronic lymphocytic leukemia patient
- Author
-
Rabizadeh, E., Bairey, O., Aviram, A., Ben-Dror, I., Shaklai, M., and Zimra, Y.
- Published
- 2001
3. The cytoskeletal network controls c-Jun translation in a UTR-dependent manner
- Author
-
Polak, P, primary, Oren, A, additional, Ben-Dror, I, additional, Steinberg, D, additional, Sapoznik, S, additional, Arditi-Duvdevany, A, additional, and Vardimon, L, additional
- Published
- 2005
- Full Text
- View/download PDF
4. Developmental changes in the expression and compartmentalization of the glucocorticoid receptor in embryonic retina.
- Author
-
Gorovits, R, primary, Ben-Dror, I, additional, Fox, L E, additional, Westphal, H M, additional, and Vardimon, L, additional
- Published
- 1994
- Full Text
- View/download PDF
5. Foreign body granulomatous inflammation increases the sensitivity of splenocytes to immunomodulation by 1,25-dihydroxyvitamin D3
- Author
-
Ben Dror, I., primary, Koren, R., additional, Liberman, U.A., additional, Erman, A., additional, Ziegler, R., additional, and Ravid, A., additional
- Published
- 1993
- Full Text
- View/download PDF
6. Developmental control of glucocorticoid receptor transcriptional activity in embryonic retina.
- Author
-
Ben-Dror, I, primary, Havazelet, N, additional, and Vardimon, L, additional
- Published
- 1993
- Full Text
- View/download PDF
7. Glutamine synthetase enhances the clearance of extracellular glutamate by the neural retina.
- Author
-
Shaked, I., Ben-Dror, I., and Vardimon, L.
- Subjects
- *
GLUTAMINE synthetase , *NEUROGLIA , *NEUROTOXICOLOGY - Abstract
Clearance of synaptic glutamate by glial cells is required for the normal function of excitatory synapses and for prevention of neurotoxicity. Although the regulatory role of glial glutamate transporters in glutamate clearance is well established, little is known about the influence of glial glutamate metabolism on this process. This study examines whether glutamine synthetase (GS), a glial-specific enzyme that amidates glutamate to glutamine, affects the uptake of glutamate. Retinal explants were incubated in the presence of [[sup 14]C]glutamate and glutamate uptake was assessed by measurement of the amount of radioactively labeled molecules within the cells and the amount of [[sup 14]C]glutamine released to the medium. An increase in GS expression in Müller glial cells, caused by induction of the endogenous gene, did not affect the amount of glutamate accumulated within the cells, but led to a dramatic increase in the amount of glutamine released. This increase, which was directly correlated with the level of GS expression, was dependent on the presence of external sodium ions, and could be completely abolished by methionine sulfoximine, a specific inhibitor of GS activity. Our results demonstrate that GS activity significantly influences the uptake of glutamate by the neural retina and suggest that this enzyme may represent an important target for neuroprotective strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
8. Basic fibroblast growth factor: a potential inhibitor of glutamine synthetase expression in injured neural tissue.
- Author
-
Kruchkova, Y., Ben-Dror, I., Herschkovitz, A., David, M., Yayon, A., and Vardimon, L.
- Subjects
- *
FIBROBLAST growth factors , *DEGENERATION (Pathology) , *CENTRAL nervous system , *GLUTAMINE synthetase - Abstract
Basic fibroblast growth factor (bFGF) was recently shown to promote the survival of neural cells and tissues, raising hopes for its therapeutic potential in degenerative disorders of the CNS. Here we examine the effect of bFGF on the expression of glutamine synthetase, a key enzyme in the detoxification of the neurotransmitter glutamate. Expression of this enzyme is regulated by systemic glucocorticoids and, in chick neural retina tissue, is restricted to Müller glial cells. We report that exogenous supply of bFGF to retinal explants inhibits hormonal induction of glutamine synthetase expression. This inhibition appears to be mediated by the c-Jun protein which accumulated, in response to bFGF, exclusively in Müller glial cells. Ischemic conditions, which reportedly stimulate the release of endogenous bFGF, also led to an increase in c-Jun protein and a decline in glutamine synthetase expression. This decline could be competitively prevented by a soluble fibroblast growth factor receptor but not by a soluble epidermal growth factor receptor. The finding that endogenous release of bFGF or its exogenous supply down-regulates glutamine synthetase expression suggests that in addition to its reported neuroprotective effect, bFGF may exacerbate glutamate mediated neurotoxicity through direct down-regulation of glutamine synthetase. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
9. A silencer element in the regulatory region of glutamine synthetase controls cell type-specific repression of gene induction by glucocorticoids.
- Author
-
Avisar, N, Shiftan, L, Ben-Dror, I, Havazelet, N, and Vardimon, L
- Abstract
Glutamine synthetase is a key enzyme in the recycling of the neurotransmitter glutamate. Expression of this enzyme is regulated by glucocorticoids, which induce a high level of glutamine synthetase in neural but not in various non-neural tissues. This is despite the fact that non-neural cells express functional glucocorticoid receptor molecules capable of inducing other target genes. Sequencing and functional analysis of the upstream region of the glutamine synthetase gene identified, 5' to the glucocorticoid response element (GRE), a 21-base pair glutamine synthetase silencer element (GSSE), which showed considerable homology with the neural restrictive silencer element NRSE. The GSSE was able to markedly repress the induction of gene transcription by glucocorticoids in non-neural cells and in embryonic neural retina. The repressive activity of the GSSE could be conferred on a heterologous GRE promoter and was orientation- and position-independent with respect to the transcriptional start site, but appeared to depend on a location proximal to the GRE. Gel-shift assays revealed that non-neural cells and cells of early embryonic retina contain a high level of GSSE binding activity and that this level declines progressively with age. Our results suggest that the GSSE might be involved in the restriction of glutamine synthetase induction by glucocorticoids to differentiated neural tissues.
- Published
- 1999
10. Molecular basis for differential expression of glutamine synthetase in retina glia and neurons
- Author
-
Grossman, R., Fox, L. E., Gorovits, R., and Ben-Dror, I.
- Published
- 1994
- Full Text
- View/download PDF
11. Exclusive Temporal Stimulation of IL-10 Expression in LPS-Stimulated Mouse Macrophages by cAMP Inducers and Type I Interferons.
- Author
-
Ernst O, Glucksam-Galnoy Y, Bhatta B, Athamna M, Ben-Dror I, Glick Y, Gerber D, and Zor T
- Subjects
- Animals, Cyclic AMP Response Element-Binding Protein physiology, Isoproterenol pharmacology, Macrophages immunology, Mice, Promoter Regions, Genetic, RAW 264.7 Cells, Response Elements physiology, Sp1 Transcription Factor physiology, Cyclic AMP physiology, Interferon Type I pharmacology, Interleukin-10 genetics, Lipopolysaccharides pharmacology, Macrophages drug effects
- Abstract
Expression of the key anti-inflammatory cytokine IL-10 in lipopolysaccharide (LPS)-stimulated macrophages is mediated by a delayed autocrine/paracrine loop of type I interferons (IFN) to ensure timely attenuation of inflammation. We have previously shown that cAMP synergizes with early IL-10 expression by LPS, but is unable to amplify the late type I IFN-dependent activity. We now examined the mechanism of this synergistic transcription in mouse macrophages at the promoter level, and explored the crosstalk between type I IFN signaling and cAMP, using the β-adrenergic receptor agonist, isoproterenol, as a cAMP inducer. We show that silencing of the type I IFN receptor enables isoproterenol to synergize with LPS also at the late phase, implying that autocrine type I IFN activity hinders synergistic augmentation of LPS-stimulated IL-10 expression by cAMP at the late phase. Furthermore, IL-10 expression in LPS-stimulated macrophages is exclusively stimulated by either IFNα or isoproterenol. We identified a set of two proximate and inter-dependent cAMP response element (CRE) sites that cooperatively regulate early IL-10 transcription in response to isoproterenol-stimulated CREB and that further synergize with a constitutive Sp1 site. At the late phase, up-regulation of Sp1 activity by LPS-stimulated type I IFN is correlated with loss of function of the CRE sites, suggesting a mechanism for the loss of synergism when LPS-stimulated macrophages switch to type I IFN-dependent IL-10 expression. This report delineates the molecular mechanism of cAMP-accelerated IL-10 transcription in LPS-stimulated murine macrophages that can limit inflammation at its onset.
- Published
- 2019
- Full Text
- View/download PDF
12. The cAMP Pathway Amplifies Early MyD88-Dependent and Type I Interferon-Independent LPS-Induced Interleukin-10 Expression in Mouse Macrophages.
- Author
-
Ernst O, Glucksam-Galnoy Y, Athamna M, Ben-Dror I, Ben-Arosh H, Levy-Rimler G, Fraser IDC, and Zor T
- Subjects
- Animals, Cells, Cultured, Female, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B metabolism, RAW 264.7 Cells, RNA, Messenger metabolism, Real-Time Polymerase Chain Reaction, Signal Transduction drug effects, Interferon Type I metabolism, Interleukin-10 metabolism, Lipopolysaccharides pharmacology, Macrophages drug effects, Macrophages metabolism, Myeloid Differentiation Factor 88 metabolism, Tumor Necrosis Factor-alpha metabolism
- Abstract
Interleukin-10 (IL-10) is a key anti-inflammatory cytokine, secreted by macrophages and other immune cells to attenuate inflammation. Autocrine type I interferons (IFNs) largely mediate the delayed expression of IL-10 by LPS-stimulated macrophages. We have previously shown that IL-10 is synergistically expressed in macrophages following a costimulus of a TLR agonist and cAMP. We now show that the cAMP pathway directly upregulates IL-10 transcription and plays an important permissive and synergistic role in early, but not late, LPS-stimulated IL-10 mRNA and protein expression in mouse macrophages and in a mouse septic shock model. Our results suggest that the loss of synergism is not due to desensitization of the cAMP inducing signal, and it is not mediated by a positive crosstalk between the cAMP and type I IFN pathways. First, cAMP elevation in LPS-treated cells decreased the secretion of type I IFN. Second, autocrine/paracrine type I IFNs induce IL-10 promoter reporter activity only additively, but not synergistically, with the cAMP pathway. IL-10 promoter reporter activity was synergistically induced by cAMP elevation in macrophages stimulated by an agonist of either TLR4, TLR2/6, or TLR7, receptors which signal via MyD88, but not by an agonist of TLR3 which signals independently of MyD88. Moreover, MyD88 knockout largely reduced the synergistic IL-10 expression, indicating that MyD88 is required for the synergism displayed by LPS with cAMP. This report delineates the temporal regulation of early cAMP-accelerated vs. late type I IFN-dependent IL-10 transcription in LPS-stimulated murine macrophages that can limit inflammation at its onset.
- Published
- 2019
- Full Text
- View/download PDF
13. 3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism.
- Author
-
Wardi J, Ernst O, Lilja A, Aeed H, Katz S, Ben-Nachum I, Ben-Dror I, Katz D, Bernadsky O, Kandhikonda R, Avni Y, Fraser IDC, Weinstain R, Biro A, and Zor T
- Subjects
- Acute Disease, Animals, Anti-Inflammatory Agents pharmacology, Antioxidants pharmacology, Cells, Cultured, Concanavalin A pharmacology, Disease Models, Animal, Mice, Mitogens pharmacology, NF-kappa B metabolism, Nitric Oxide Synthase Type II metabolism, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Treatment Outcome, Tumor Necrosis Factor-alpha metabolism, Benzamides pharmacology, Hepatitis metabolism, Hepatitis prevention & control, Macrophages drug effects, Macrophages physiology
- Abstract
Background and Aims: Concanavalin A is known to activate T cells and to cause liver injury and hepatitis, mediated in part by secretion of TNFα from macrophages. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been shown to prevent tissue damage in various animal models of inflammation. The objectives of this study were to evaluate the efficacy and mechanism of the PARP-1 inhibitor 3-aminobenzamide (3-AB) in preventing concanavalin A-induced liver damage., Methods: We tested the in vivo effects of 3-AB on concanavalin A-treated mice, its effects on lipopolysaccharide (LPS)-stimulated macrophages in culture, and its ability to act as a scavenger in in vitro assays., Results: 3-AB markedly reduced inflammation, oxidative stress, and liver tissue damage in concanavalin A-treated mice. In LPS-stimulated RAW264.7 macrophages, 3-AB inhibited NFκB transcriptional activity and subsequent expression of TNFα and iNOS and blocked NO production. In vitro, 3-AB acted as a hydrogen peroxide scavenger. The ROS scavenger N-acetylcysteine (NAC) and the ROS formation inhibitor diphenyleneiodonium (DPI) also inhibited TNFα expression in stimulated macrophages, but unlike 3-AB, NAC and DPI were unable to abolish NFκB activity. PARP-1 knockout failed to affect NFκB and TNFα suppression by 3-AB in stimulated macrophages., Conclusions: Our results suggest that 3-AB has a therapeutic effect on concanavalin A-induced liver injury by inhibiting expression of the key pro-inflammatory cytokine TNFα, via PARP-1-independent NFκB suppression and via an NFκB-independent anti-oxidative mechanism.
- Published
- 2018
- Full Text
- View/download PDF
14. MicroRNA 10b promotes abnormal expression of the proto-oncogene c-Jun in metastatic breast cancer cells.
- Author
-
Knirsh R, Ben-Dror I, Modai S, Shomron N, and Vardimon L
- Subjects
- Breast Neoplasms pathology, Cadherins metabolism, Carcinogenesis, Cell Movement, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Humans, MCF-7 Cells, Neoplasm Metastasis, Proto-Oncogene Mas, Proto-Oncogene Proteins c-jun genetics, RNA, Small Interfering genetics, Up-Regulation, Breast Neoplasms metabolism, Cytoskeleton metabolism, MicroRNAs genetics, Neurofibromin 1 metabolism, Proto-Oncogene Proteins c-jun metabolism, rhoC GTP-Binding Protein metabolism
- Abstract
MicroRNAs have been shown to act as oncogenes or tumor suppressers via various cellular pathways. Specifically, in breast cancer, upregulation of miR-10b is positively associated with aggressiveness of tumors. However, the mechanism by which miR-10b contributes to cell malignancy is largely unknown. Here we show that at the receiving end of the miR-10b pathway is the proto-oncogene c-Jun, a transcription factor that plays a critical role in stimulation of cell proliferation and tumor progression. c-Jun is known to be translationally activated by loss of cell contacts or restructuring of the cytoskeleton. A comprehensive analysis of miRNA expression exhibited a significant increase in miR-10b expression. This was supported by analysis of breast cancer cells, which showed that loss of E-cadherin in metastatic cells is accompanied by elevation of miR-10b and interestingly, by a marked increase in accumulation of c-Jun. Silencing miR-10b in metastatic breast cancer cells leads to a decline in c-Jun expression, whereas overexpression of miR-10b in HaCaT cells is sufficient to elevate the accumulation of c-Jun. The increase in c-Jun protein accumulation in metastatic cells is not accompanied by an increase in c-Jun mRNA and is not dependent on MAPK activity. Knockdown and overexpression experiments revealed that the increase is mediated by NF1 and RhoC, downstream targets of miR-10b that affect cytoskeletal dynamics through the ROCK pathway. Overall, we show the ability of miR-10b to activate the expression of c-Jun through RhoC and NF1, which represents a novel pathway for promoting migration and invasion of human cancer cells.
- Published
- 2016
- Full Text
- View/download PDF
15. Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation.
- Author
-
Blau L, Knirsh R, Ben-Dror I, Oren S, Kuphal S, Hau P, Proescholdt M, Bosserhoff AK, and Vardimon L
- Subjects
- Animals, Blotting, Western, Cells, Cultured, Gene Expression Regulation, Neoplastic genetics, Humans, Immunohistochemistry, Luciferases, Protein Biosynthesis genetics, Rats, Rats, Sprague-Dawley, Gene Expression Regulation, Neoplastic physiology, Glioblastoma metabolism, Protein Biosynthesis physiology, Proto-Oncogene Proteins c-jun metabolism, Ribosomes metabolism
- Abstract
Although the protooncogene c-Jun plays a critical role in cell proliferation, cell death, and malignant transformation, DNA microarray screens have identified only a few human cancer types with aberrant expression of c-Jun. Here, we show that c-Jun accumulation is robustly elevated in human glioblastoma and that this increase contributes to the malignant properties of the cells. Most importantly, the increase in c-Jun protein accumulation occurs with no corresponding increase in c-Jun mRNA or the half-life of the c-Jun protein but, rather, in the translatability of the transcript. The c-Jun 5'UTR harbors a potent internal ribosomal entry site (IRES) with a virus-like IRES domain that directs cap-independent translation in glioblastoma cells. Accumulation of c-Jun is not dependent on MAPK activity but can be stimulated by a cytoskeleton-dependent pathway. Our findings provide evidence that human c-Jun is an IRES-containing cellular transcript that contributes to cancer development through translational activation. This previously undescribed mechanism of c-Jun regulation might also be relevant to other types of human cancer and offers unique potential targets for therapy.
- Published
- 2012
- Full Text
- View/download PDF
16. Alterations of heart rate variability in women with overactive bladder syndrome.
- Author
-
Ben-Dror I, Weissman A, Leurer MK, Eldor-Itskovitz J, and Lowenstein L
- Subjects
- Adult, Aged, Autonomic Nervous System physiology, Case-Control Studies, Female, Humans, Middle Aged, Urinary Bladder innervation, Urinary Bladder physiopathology, Urination physiology, Electrocardiography, Heart Rate physiology, Urinary Bladder, Overactive physiopathology
- Abstract
Introduction and Hypothesis: Our objective was to compare autonomic nervous system function between women with an overactive bladder (OAB) and control participants during regulated bladder filling., Methods: Twenty-four women, nine with OAB and 15 without (control), were instructed to drink 1.5 l of water at a rate of 250 ml every 5 min during continuous electrocardiogram (ECG) monitoring. Participants were asked to indicate first sensations of filling (FSF), first desire to void (FDV), strong desire to void (SDV), and maximal bladder capacity (MC). ECG signals were used to assess heart rate variability, which were analyzed in time and frequency domains using the fast Fourier transform. The low-frequency (LF)and high-frequency (HF) spectral bands were used to asses sympathetic and parasympathetic pathways, respectively., Results: During the bladder-filling phase, women with OAB had significantly lower LF values (at the MC phase 5.4 ± 1.4 ms(2)/Hz vs. 6.4 ± 0.6 ms(2)/Hz in the control group, p = 0.02). In the control group, LF increased continuously, whereas in the OAB group, LF increased until the sensation of SDV and then abruptly decreased to baseline values. MC was lower in women with OAB (372 ± 153 ml vs. 592 ± 298 ml, p < 0.05, respectively)., Conclusions: Reduced sympathetic tone in women with OAB may explain their attainment of lower volumes of MC and their sensation of urgency. The rapid decrease in sympathetic neural activity that accompanies the sensation of an SDV may be related to the pathophysiology of the urgency symptom in these women.
- Published
- 2012
- Full Text
- View/download PDF
17. [The role of physical therapy in the treatment of female sexual dysfunction].
- Author
-
Rosenbaum TY and Ben-Dror I
- Subjects
- Adult, Dyspareunia rehabilitation, Dyspareunia therapy, Female, Humans, Middle Aged, Sexual Behavior, Sexual Dysfunction, Physiological rehabilitation, Sexual Dysfunction, Physiological therapy, Vaginismus psychology, Vaginismus rehabilitation, Vaginismus therapy, Young Adult, Physical Therapy Modalities
- Abstract
Healthy sexual function requires physical, mental, and emotional well-being. Physical presentations that may limit sexual activity include decreased mobility, alterations in sensation, decreased genital circulation and pain. Physical therapists play an important role in facilitating optimal sexual function by providing treatment to restore function, improve mobility and relieve pain. This article illustrates, through four case reports, the importance of physiotherapy in the multidisciplinary approach to the treatment of female sexual dysfunction.
- Published
- 2009
18. Loss of E-cadherin-mediated cell-cell contacts activates a novel mechanism for up-regulation of the proto-oncogene c-Jun.
- Author
-
Knirsh R, Ben-Dror I, Spangler B, Matthews GD, Kuphal S, Bosserhoff AK, and Vardimon L
- Subjects
- Animals, Cell Line, Chickens, Cytoskeleton metabolism, Humans, Mice, Mitogen-Activated Protein Kinases metabolism, Protein Biosynthesis, Proto-Oncogene Mas, Proto-Oncogene Proteins c-jun metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Transcription, Genetic, Cadherins metabolism, Cell Communication, Proto-Oncogene Proteins c-jun genetics, Up-Regulation genetics
- Abstract
Loss of E-cadherin-mediated cell-cell contacts can elicit a signaling pathway that leads to acquisition of an invasive phenotype. Here, we show that at the receiving end of this pathway is the proto-oncogene c-Jun, a member of the activator protein-1 family of transcription factors that play a key role in stimulation of cell proliferation and tumor promotion. Cell separation or abrogation of E-cadherin-mediated cell-cell contacts both cause a dramatic increase in accumulation of the c-Jun protein. Unlike growth factors that enhance the expression of c-Jun by activating the transcription of the c-jun gene, the cell contact-dependent increase in c-Jun accumulation is not accompanied by a corresponding increase in c-Jun mRNA or c-Jun protein stability but rather in the translatability of the c-Jun transcript. Consistently, the increase in c-Jun accumulation is not dependent on activation of the mitogen-activated protein kinase or beta-catenin pathways but is mediated by signals triggered by the restructured cytoskeleton. Depolymerization of the cytoskeleton can mimic the effect of cell separation and cause a dramatic increase in c-Jun accumulation, whereas Taxol inhibits the cell contact-dependent increase. This novel mechanism of c-Jun regulation seems to underlie the robust overexpression of c-Jun in tumor cells of patients with colon carcinoma.
- Published
- 2009
- Full Text
- View/download PDF
19. Dual role of NRSF/REST in activation and repression of the glucocorticoid response.
- Author
-
Abramovitz L, Shapira T, Ben-Dror I, Dror V, Granot L, Rousso T, Landoy E, Blau L, Thiel G, and Vardimon L
- Subjects
- Animals, Binding Sites genetics, Blotting, Western, COS Cells, Cell Line, Tumor, Cells, Cultured, Chickens, Chlorocebus aethiops, Genetic Vectors genetics, HeLa Cells, Humans, Immunoprecipitation, Promoter Regions, Genetic genetics, Receptors, Glucocorticoid metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, Retina cytology, Retina drug effects, Retina metabolism, Transcription Factors genetics, Transcription Factors metabolism, Transcription, Genetic drug effects, Transcriptional Activation, Yeasts genetics, Yeasts metabolism, Gene Expression Regulation drug effects, Glucocorticoids pharmacology, Repressor Proteins physiology, Transcription Factors physiology
- Abstract
Restriction of glutamine synthetase to the nervous system is mainly achieved through the mutual function of the glucocorticoid receptor and the neural restrictive silencing factor, NRSF/REST. Glucocorticoids induce glutamine synthetase expression in neural tissues while NRSF/REST represses the hormonal response in non-neural cells. NRSF/REST is a modular protein that contains two independent repression domains, at the N and C termini of the molecule, and is dominantly expressed in nonneural cells. Neural tissues express however splice variants, REST4/5, which contain the repression domain at the N, but not at the C terminus of the molecule. Here we show that full-length NRSF/REST or its C-terminal domain can inhibit almost completely the induction of gene transcription by glucocorticoids. By contrast, the N-terminal domain not only fails to repress the hormonal response but rather stimulates it markedly. The inductive activity of the N-terminal domain is mediated by hBrm, which is recruited to the promoter only in the concomitant presence of GR. Importantly, a similar inductive activity is also exerted by the splice variant REST4. These findings raise the possibility that NRSF/REST exhibits a dual role in regulation of glutamine synthetase. It represses gene induction in nonneural cells and enhances the hormonal response, via its splice variant, in the nervous system.
- Published
- 2008
- Full Text
- View/download PDF
20. Cytoskeletal and cell contact control of the glucocorticoid pathway.
- Author
-
Vardimon L, Ben-Dror I, Oren A, and Polak P
- Subjects
- Animals, Cell Division, Genes, jun, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid physiology, Cell Communication physiology, Cytoskeleton physiology, Glucocorticoids physiology
- Abstract
The cytoskeleton is a dynamic network that undergoes restructuring during a variety of cellular events including cell contact formation, cell invasion and the mitotic phase of the cell cycle. Here, we review the contribution of the cytoskeletal network to the inductive activity of glucocorticoids by focusing on the hormonal control of glutamine synthetase in the chick neural retina. Depolymerization of the cytoskeleton in cells of the intact retinal tissue inhibits the hormonal induction of glutamine synthetase, but does not alter the cellular amount of the glucocorticoid-receptor protein or the ability of the receptor molecules to translocate into the nucleus. Inhibition of glutamine synthetase induction occurs via a mechanism that involves elevation of c-Jun protein accumulation and repression of glucocorticoid-receptor transcriptional activity. Unlike growth factors and other c-Jun inducing stimuli that control the transcription of the c-Jun gene, depolymerization of the cytoskeleton elevates c-Jun accumulation by upregulating the translation of the c-Jun transcript. We postulate that the cytoskeletal-dependent increase in c-Jun accumulation is involved in cell contact control of both cell proliferation and transcriptional activity of the glucocorticoid-receptor protein.
- Published
- 2006
- Full Text
- View/download PDF
21. Glucocorticoid control of glial gene expression.
- Author
-
Vardimon L, Ben-Dror I, Avisar N, Oren A, and Shiftan L
- Subjects
- Animals, Cell Communication physiology, Glucocorticoids biosynthesis, Humans, Neuroglia metabolism, Neurons metabolism, Neurons physiology, Signal Transduction physiology, Gene Expression Regulation genetics, Glucocorticoids genetics, Glucocorticoids physiology, Neuroglia physiology
- Abstract
The glucocorticoid signaling pathway is responsive to a considerable number of internal and external signals and can therefore establish diverse patterns of gene expression. A glial-specific pattern, for example, is shown by the glucocorticoid-inducible gene glutamine synthetase. The enzyme is expressed at a particularly high level in glial cells, where it catalyzes the recycling of the neurotransmitter glutamate, and at a low level in most other cells, for housekeeping duties. Glial specificity of glutamine synthetase induction is achieved by the use of positive and negative regulatory elements, a glucocorticoid response element and a neural restrictive silencer element. Though not glial specific by themselves, these elements may establish a glial-specific pattern of expression through their mutual activity and their combined effect. The inductive activity of glucocorticoids is markedly repressed by the c-Jun protein, which is expressed at relatively high levels in proliferating glial cells. The signaling pathway of c-Jun is activated by the disruption of glia-neuron cell contacts, by transformation with v-src, and in proliferating retinal cells of early embryonic ages. The c-Jun protein inhibits the transcriptional activity of the glucocorticoid receptor and thus represses glutamine synthetase expression. This repressive mechanism might also affect the ability of glial cells to cope with glutamate neurotoxicity in injured tissues., (Copyright 1999 John Wiley & Sons, Inc.)
- Published
- 1999
- Full Text
- View/download PDF
22. The cytoskeletal network controls c-Jun expression and glucocorticoid receptor transcriptional activity in an antagonistic and cell-type-specific manner.
- Author
-
Oren A, Herschkovitz A, Ben-Dror I, Holdengreber V, Ben-Shaul Y, Seger R, and Vardimon L
- Subjects
- Animals, Chick Embryo, Cytoskeleton drug effects, Glutamate-Ammonia Ligase biosynthesis, Neuroglia metabolism, Proto-Oncogene Proteins c-jun genetics, Receptors, Glucocorticoid genetics, Retina drug effects, Signal Transduction, Cytoskeleton physiology, Gene Expression Regulation, Neoplastic drug effects, Proto-Oncogene Proteins c-jun biosynthesis, Receptors, Glucocorticoid biosynthesis, Transcription, Genetic drug effects
- Abstract
The physical and functional link between adhesion molecules and the cytoskeletal network suggests that the cytoskeleton might mediate the transduction of cell-to-cell contact signals, which often regulate growth and differentiation in an antagonistic manner. Depolymerization of the cytoskeleton in confluent cell cultures is reportedly sufficient to initiate DNA synthesis. Here we show that depolymerization of the cytoskeleton is also sufficient to repress differentiation-specific gene expression. Glutamine synthetase is a glia-specific differentiation marker gene whose expression in the retinal tissue is regulated by glucocorticoids and is ultimately dependent on glia-neuron cell contacts. Depolymerization of the actin or microtubule network in cells of the intact retina mimics the effects of cell separation, repressing glutamine synthetase induction by a mechanism that involves induction of c-Jun and inhibition of glucocorticoid receptor transcriptional activity. Depolymerization of the cytoskeleton activates JNK and p38 mitogen-activated protein kinase and induces c-Jun expression by a signaling pathway that depends on tyrosine kinase activity. Induction of c-Jun expression is restricted to Müller glial cells, the only cells in the tissue that express glutamine synthetase and maintain the ability to proliferate upon cell separation. Our results suggest that the cytoskeletal network might play a part in the transduction of cell contact signals to the nucleus.
- Published
- 1999
- Full Text
- View/download PDF
23. Effect of the cytostatic butyric acid pro-drug, pivaloyloxymethyl butyrate, on the tumorigenicity of cancer cells.
- Author
-
Aviram A, Rephaeli A, Shaklai M, Nudelman A, Ben-Dror I, Maron L, and Rabizadeh E
- Subjects
- Animals, Genes, jun drug effects, Genes, myc drug effects, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Neoplasm drug effects, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Butyrates pharmacology, Carcinoma, Lewis Lung drug therapy, Gene Expression Regulation, Neoplastic drug effects, Leukemia, Myelomonocytic, Acute drug therapy
- Abstract
Previously we have shown that pivaloyloxymethyl butyrate (AN-9), a pro-drug of butyric acid (BA), is a differentiation-inducing agent in a variety of cells. In this report, we demonstrate that AN-9 is a cytostatic but not cytotoxic agent in a myelomonocytic cell line (WEHI); thus, the cells were growth-arrested and differentiated. These late changes in the cells were preceded by changes in the expression of the early regulatory genes, c-myc and c-jun. Although initiation of all these events had already occurred after 1 h exposure to AN-9, the tumorigenicity of these cells tested in Balb/c mice was not affected. A marked reduction in the tumorigenicity of AN-9-treated cells was observed after 4 h of exposure. Exposure of the highly metastatic subclone of Lewis lung carcinoma (3LLD122) to AN-9 resulted in a very pronounced effect on the tumorigenicity of these cells tested in C57BL mice. Unlike WEHI cells, the tumorigenicity of 3LLD122 was almost completely diminished after 1 h of exposure. In both cell types a 10-fold higher concentration of BA did not affect the tumorigenicity of the cells as did AN-9.
- Published
- 1997
- Full Text
- View/download PDF
24. Molecular basis for differential expression of glutamine synthetase in retina glia and neurons.
- Author
-
Grossman R, Fox LE, Gorovits R, Ben-Dror I, Reisfeld S, and Vardimon L
- Subjects
- Animals, Chick Embryo, RNA, Messenger metabolism, Retina cytology, Glutamate-Ammonia Ligase biosynthesis, Neuroglia enzymology, Neurons enzymology, Receptors, Glucocorticoid genetics, Retina enzymology, Transcription, Genetic
- Abstract
Glutamine synthetase (GS) is a differentiation marker of retina glial cell. It is expressed in the chicken neural retina at a particularly high level, is inducible by glucocorticoids and is always confined to Müller glia. This study investigated the molecular basis for tissue and cell-type specific expression of the GS gene. A high level of GS expression in the retina was found to coincide with the accumulation of a relatively high level of GS mRNA in this tissue. The gliatoxic agent alpha-aminoadipic acid, which can selectively destroy glia cells, was used to demonstrate that restriction of GS induction to Müller glia is controlled at a transcriptional level. Cortisol could induce accumulation of GS mRNA and transcription of the GS gene in Müller glia but not in retina neurons. Glia and neurons were also found to differ in their ability to express the glucocorticoid inducible CAT construct, p delta G46TCO, which is controlled by a 'simple GRE' promoter. When introduced into cells of retina tissue, this construct was cortisol-inducible in glia whereas in neurons it was only slightly inducible or not at all. Introduction of a glucocorticoid receptor expression vector into the cells facilitated induction of the CAT construct in neurons. Analysis by immunoblotting revealed that expression of the glucocorticoid receptor protein is predominantly restricted to Müller glia. These results suggest that differential levels of glucocorticoid receptor expression in glia and neurons might be the basis for cell-type specific induction of GS.
- Published
- 1994
- Full Text
- View/download PDF
25. Molecular control of glutamine synthetase expression in the developing retina tissue.
- Author
-
Vardimon L, Ben-Dror I, Havazelet N, and Fox LE
- Subjects
- Animals, Cell Division, Enzyme Induction, Models, Biological, Receptors, Glucocorticoid genetics, Retina embryology, Transcription, Genetic, Glutamate-Ammonia Ligase metabolism, Retina enzymology
- Abstract
Glutamine synthetase is a differentiation marker of the neural retina, whose expression is restricted to Müller glia cells, is inducible by glucocorticoids and is dependent on tissue development. The retina tissue acquires the competence to express GS in response to glucocorticoids with development, although the level of hormone binding activity in the cells does not alter with age. Using CAT constructs that are controlled by "simple GRE" promoters we demonstrated that glucocorticoid receptor transcription activity in retina cells increases with development. The increase in receptor activity correlates directly with the increase in inducibility of the glutamine synthetase gene and inversely with the rate of retina cell proliferation. At early developmental ages, when retina cells are still proliferating, the glucocorticoid receptor is transcriptionally inactive and glutamine synthetase expression cannot be induced. Receptor activity increases progressively with development and by day 12, when cell proliferation ceases, competence for glutamine synthetase induction is high. This competence for glutamine synthetase induction can be repressed by overexpressing the oncogene v-src, which stimulates retina cell proliferation. We discuss possible mechanisms for developmental-dependent modulation of glucocorticoid receptor transcriptional activity.
- Published
- 1993
- Full Text
- View/download PDF
26. Word identification in isolation and in context by college dyslexic students.
- Author
-
Ben-Dror I, Pollatsek A, and Scarpati S
- Subjects
- Adult, Dyslexia psychology, Female, Humans, Male, Memory, Models, Psychological, Dyslexia diagnosis, Language Tests, Reading
- Abstract
College dyslexic students (DYS) were compared to chronological age (CA)-matched and to reading age (RA)-matched control groups on tasks assessing naming of words and nonwords, regular and irregular words, and the use of context in word identification. The DYS group had the slowest naming latency for words in all tasks. In addition, they had extreme difficulty in naming nonwords, which in terms of the dual-route model for word recognition indicates impairment in the indirect route to the lexicon. However, they displayed a regularity effect in reading regular and irregular words and thus apparently utilized the indirect route in reading words. Correlational data supported the conclusion that the data are in conflict with the traditional dual-route model, and an alternative conceptualization is suggested. The use of context is discussed in terms of the interactive-compensatory model (Stanovich, 1980) and findings were generally supportive of the model. The DYS subjects of the present study appeared to be different from the RA controls and their performance did not support a developmental-lag model for explaining their reading problems.
- Published
- 1991
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.