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Sample records for regulates neurite growth

  1. Shoc2/Sur8 protein regulates neurite outgrowth.

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    Gonzalo Leon

    Full Text Available The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.

  2. The neurite growth inhibitory effects of soluble TNFα on developing sympathetic neurons are dependent on developmental age.

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    Nolan, Aoife M; Collins, Louise M; Wyatt, Sean L; Gutierrez, Humberto; O'Keeffe, Gerard W

    2014-01-01

    During development, the growth of neural processes is regulated by an array of cellular and molecular mechanisms which influence growth rate, direction and branching. Recently, many members of the TNF superfamily have been shown to be key regulators of neurite growth during development. The founder member of this family, TNFα can both promote and inhibit neurite growth depending on the cellular context. Specifically, transmembrane TNFα promotes neurite growth, while soluble TNFα inhibits it. While the growth promoting effects of TNFα are restricted to a defined developmental window of early postnatal development, whether the growth inhibitory effects of soluble TNFα occur throughout development is unknown. In this study we used the extensively studied, well characterised neurons of the superior cervical ganglion to show that the growth inhibitory effects of soluble TNFα are restricted to a specific period of late embryonic and early postnatal development. Furthermore, we show that this growth inhibitory effect of soluble TNFα requires NF-κB signalling at all developmental stages at which soluble TNFα inhibits neurite growth. These findings raise the possibility that increases in the amount of soluble TNFα in vivo, for example as a result of maternal inflammation, could negatively affect neurite growth in developing neurons at specific stages of development. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  3. Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth

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    Povlsen, Gro Klitgaard; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies...... this NCAM-180-induced EGFR down-regulation involves increased EGFR ubiquitination and lysosomal EGFR degradation. Furthermore, NCAM-180-mediated EGFR down-regulation requires NCAM homophilic binding and interactions of the cytoplasmic domain of NCAM-180 with intracellular interaction partners, but does...

  4. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements

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    Wood, Matthew D.; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m-1) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca2+) or PBS (no Ca2+). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata.

  5. Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone.

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    O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A; Lawless, Sean M; Williams, Rebecca M; Zipfel, Warren R; Olson, Eric C

    2012-07-07

    The secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction. The total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite "exclusion zone" which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs. These findings indicate Reelin promotes directional dendritic growth into

  6. C. elegans fmi-1/flamingo and Wnt pathway components interact genetically to control the anteroposterior neurite growth of the VD GABAergic neurons.

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    Huarcaya Najarro, Elvis; Ackley, Brian D

    2013-05-01

    Directed axonal growth is essential to establish neuronal networks. During the early development of the VD neurons, an anterior neurite that will become the VD axon extends along the anteroposterior (A/P) axis in the ventral nerve cord (VNC) in Caenorhabditis elegans. Little is known about the cellular and molecular mechanisms that are important for correct neurite growth in the VNC. In fmi-1/flamingo mutant animals, we observed that some postembryonically born VD neurons had a posterior neurite instead of a normal anterior neurite, which caused aberrant VD commissure patterning along the A/P axis. In addition, VD anterior neurites had underextension defects in the VNC in fmi-1 animals, whereas VD commissure growth along the dorsoventral (D/V) axis occurred normally in these animals, suggesting that fmi-1 is important for neurite growth along the A/P axis but not the D/V axis. We also uncovered unknown details of the early development of the VD neurons, indicating that the neurite defects arose during their early development. Interestingly, though fmi-1 is present at this time in the VNC, we did not observe FMI-1 in the VD neurons themselves, suggesting that fmi-1 might be working in a cell non-autonomous fashion. Furthermore, fmi-1 appears to be working in a novel pathway, independently from the planar cell polarity pathway and in parallel to lin-17/frizzled and dsh-1/dishevelled, to determine the direction of neurite growth. Our findings indicate that redundant developmental pathways regulate neurite growth in the VNC in C. elegans. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels

    OpenAIRE

    Conovaloff, Aaron W.; Beier, Brooke L.; Irazoqui, Pedro P.; Panitch, Alyssa

    2011-01-01

    Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. F...

  8. Neurotrophins differentially stimulate the growth of cochlear neurites on collagen surfaces and in gels☆

    Science.gov (United States)

    Xie, Joanna; Pak, Kwang; Evans, Amaretta; Kamgar-Parsi, Andy; Fausti, Stephen; Mullen, Lina; Ryan, Allen Frederic

    2013-01-01

    The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant. PMID:24459465

  9. Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

    Directory of Open Access Journals (Sweden)

    Jingyu Jin

    2018-01-01

    Full Text Available As one major component of extracellular matrix (ECM in the central nervous system, chondroitin sulfate proteoglycans (CSPGs have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite outgrowth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron (CGN culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, including cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concentration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy (IRM which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.

  10. The prescriptions from Shenghui soup enhanced neurite growth and GAP-43 expression level in PC12 cells.

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    Zhang, Qi; Zhang, Zi-Jian; Wang, Xing-Hua; Ma, Jie; Song, Yue-Han; Liang, Mi; Lin, Sen-Xiang; Zhao, Jie; Zhang, Ao-Zhe; Li, Feng; Hua, Qian

    2016-09-20

    Shenghui soup is a traditional Chinese herbal medicine used in clinic for the treatment of forgetfulness. In order to understanding the prescription principle, the effects of "tonifying qi and strengthening spleen" group (TQSS) including Poria cocos (Schw.) Wolf. and Panax ginseng C.A.Mey and "eliminating phlegm and strengthening intelligence" group (EPSI) composed of Polygala tenuifolia Willd., Acorus calamus L. and Sinapis alba L from the herb complex on neurite growth in PC12 cells, two disassembled prescriptions derived from Shenghui soup and their molecular mechanisms were investigated. Firstly, CCK-8 kit was used to detect the impact of the two prescriptions on PC12 cell viability; and Flow cytometry was performed to measure the cell apoptosis when PC12 cells were treated with these drugs. Secondly, the effect of the two prescriptions on the differentiation of PC12 cells was observed. Finally, the mRNA and protein expression levels of GAP-43 were analyzed by RT-PCR and western blot, respectively. "Tonifying qi and strengthening spleen" prescription decreased cell viability in a dose-dependent manner, but had no significant effect on cell apoptosis. Meanwhile, it could improve neurite growth and elevate the mRNA and protein expression level of GAP-43. "Eliminating phlegm and strengthening intelligence" prescription also exerted the similar effects on cell viability and apoptosis. Furthermore, it could also enhance cell neurite growth, with a higher expression level of GAP-43 mRNA and protein. "Tonifying qi and strengthening spleen" and "eliminating phlegm and strengthening intelligence" prescriptions from Shenghui soup have a positive effect on neurite growth. Their effects are related to the up-regulating expression of GAP-43.

  11. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

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    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China); Feng, Xudong, E-mail: xudong.feng@childrens.harvard.edu [Department of Medicine, Children' s Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (United States); Xia, Qing, E-mail: xqing@hsc.pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2015-06-10

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.

  12. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    International Nuclear Information System (INIS)

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin; Feng, Xudong; Xia, Qing

    2015-01-01

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress

  13. The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

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    Carlos A. Díaz-Balzac

    2015-06-01

    Full Text Available Neurite branching is essential for correct assembly of neural circuits, yet it remains a poorly understood process. For example, the neural cell adhesion molecule KAL-1/anosmin-1, which is mutated in Kallmann syndrome, regulates neurite branching through mechanisms largely unknown. Here, we show that KAL-1/anosmin-1 mediates neurite branching as an autocrine co-factor with EGL-17/FGF through a receptor complex consisting of the conserved cell adhesion molecule SAX-7/L1CAM and the fibroblast growth factor receptor EGL-15/FGFR. This protein complex, which appears conserved in humans, requires the immunoglobulin (Ig domains of SAX-7/L1CAM and the FN(III domains of KAL-1/anosmin-1 for formation in vitro as well as function in vivo. The kinase domain of the EGL-15/FGFR is required for branching, and genetic evidence suggests that ras-mediated signaling downstream of EGL-15/FGFR is necessary to effect branching. Our studies establish a molecular pathway that regulates neurite branching during development of the nervous system.

  14. Activation of transglutaminase 2 by nerve growth factor in differentiating neuroblastoma cells: A role in cell survival and neurite outgrowth.

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    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2018-02-05

    NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

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    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  16. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

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    Chen, Chih-Hao [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Neurosurgery, Department of Surgery, Kaohsiung Veterans General Hospital, Taiwan, ROC (China); Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Kuo, Shyh Ming [Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Guei-Sheung [Centre for Eye Research Australia, University of Melbourne (Australia); Chen, Wan-Nan U. [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China); Chuang, Chin-Wen [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Li-Feng, E-mail: liulf@isu.edu.tw [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. Black-Right-Pointing-Pointer Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. Black-Right-Pointing-Pointer 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 {mu}m porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  17. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    International Nuclear Information System (INIS)

    Chen, Chih-Hao; Kuo, Shyh Ming; Liu, Guei-Sheung; Chen, Wan-Nan U.; Chuang, Chin-Wen; Liu, Li-Feng

    2012-01-01

    Highlights: ► Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. ► Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. ► 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 μm porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  18. Inhibitory effects of brain-derived neurotrophic factor precursor on viability and neurite growth of murine hippocampal neurons

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    Jia CHEN

    2014-10-01

    Full Text Available Objective To explore the mediation effect of p75 neurotrophin receptor (p75NTR in the effect of brainderived neurotrophic factor precursor (proBDNF on viability and neurite growth of murine hippocampal neurons. Methods  Hippocampal neurons were obtained from p75NTR+/+ and p75NTR-/- 18-day mice and primarily cultured. For p75NTR+/+ neurons, three experimental groups were set, i.e. control, proBDNF (30ng/ml, and proBDNF (30ng/ml+p75/Fc (30µg/ml groups. For p75NTR-/- neurons, two experimental groups were set, i.e. control and proBDNF (30ng/ml groups. MTT assays were performed after 24h to examine the viability of neonatal primary neurons. Immunofluorescent staining was conducted after 72h to investigate the neurite length. Results With MAP2 and DAPI double fluorescent staining it was identified that the neonatal hippocampal neurons were successfully cultured in vitro with high purity. For viability assay of p75NTR+/+ neurons, it was found that the absorbance value at 570nm (A570 in proBDNF group was significantly lower than that in control group (P0.05. With neurite growth assay of p75NTR+/+ neurons, it was found that the neurite length in proBDNF group was significantly shorter than that in control group (P0.05. With neurite growth assay of p75NTR-/- neurons, no difference in neurite length was observed between proBDNF group and control group. Conclusion proBDNF may inhibit the neuronal viability and neurite growth via p75NTR. DOI: 10.11855/j.issn.0577-7402.2014.09.03

  19. Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.

    Science.gov (United States)

    Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi

    2015-11-01

    The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    International Nuclear Information System (INIS)

    Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

    2010-01-01

    Research highlights: → Extracellular Nm23H1 stimulates nerve growth. → Extracellular Nm23H1 provides pathfinding cues to growth cones. → The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. → The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  1. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

    2010-07-16

    Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  2. Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.

    Science.gov (United States)

    Wang, Y; Qiu, B; Liu, J; Zhu, Wei-Guo; Zhu, S

    2014-09-26

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.

    Directory of Open Access Journals (Sweden)

    Tamaki Ishima

    Full Text Available In addition to both the α1 adrenergic receptor and N-methyl-D-aspartate (NMDA receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1 and 2. In this study, we examined the effects of ifenprodil on nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Ifenprodil significantly potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner. In contrast, the α1 adrenergic receptor antagonist, prazosin and the NMDA receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly, ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced by the inositol 1,4,5-triphosphate (IP(3 receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+, blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+ in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3 receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.

  4. Characterization of BASP1-mediated neurite outgrowth

    DEFF Research Database (Denmark)

    Korshunova, Irina; Caroni, Pico; Kolkova, Kateryna

    2008-01-01

    The brain acid-soluble protein BASP1 (CAP-23, NAP-22) belongs to the family of growth-associated proteins, which also includes GAP-43, a protein recently shown to regulate neural cell adhesion molecule (NCAM)-mediated neurite outgrowth. Here, the effects of BASP1 overexpression were investigated...

  5. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of); Jang, Deok-Jin [Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711 (Korea, Republic of); Lee, Jin-A, E-mail: leeja@hnu.kr [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of)

    2013-08-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

  6. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    International Nuclear Information System (INIS)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan; Jang, Deok-Jin; Lee, Jin-A

    2013-01-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival

  7. cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down-regulation of TC10 activity at the plasma membrane and neurite outgrowth.

    Science.gov (United States)

    Koinuma, Shingo; Takeuchi, Kohei; Wada, Naoyuki; Nakamura, Takeshi

    2017-11-01

    Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP-induced signaling leading to the regulation of membrane trafficking remains unknown. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF-treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP addition in neuronal cells. TC10 was locally inactivated at extending neurite tips in cAMP-treated PC12 cells. TC10 depletion led to a decrease in cAMP-induced neurite outgrowth. Constitutively active TC10 could not rescue this growth reduction, supporting our model for a role of GTP hydrolysis of TC10 in neuritogenesis by accelerating vesicle fusion. The cAMP-induced TC10 inactivation was mediated by PKA. Considering cAMP-induced RhoA inactivation, we found that p190B, but not p190A, mediated inactivation of TC10 and RhoA. Upon cAMP treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1-N17 expression reduced cAMP-induced TC10 inactivation. Together, the PKA-STEF-Rac1-p190B pathway leading to inactivation of TC10 and RhoA at the plasma membrane plays an important role in cAMP-induced neurite outgrowth. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  8. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells.

    Science.gov (United States)

    Tang, Li-li; Wang, Rui; Tang, Xi-can

    2005-06-01

    To study the effects of huperzine A (HupA) on neuritogenic activity and the expression of nerve growth factor (NGF). After being treated with 10 micromol/L HupA, neurite outgrowth of PC12 cells was observed and counted under phase-contrast microscopy. Mitogenic activity was assayed by [3H]thymidine incorporation. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. AChE activity, mRNA and protein expression were measured by the Ellman method, RT-PCR, and Western blot, respectively. NGF mRNA and protein levels were determined by RT-PCR and ELISA assays. Treatment of PC12 cells with 10 micromol/L HupA for 48 h markedly increased the number of neurite-bearing cells, but caused no significant alteration in cell viability or other signs of cytotoxicity. In addition to inhibiting AChE activity, 10 micromol/L HupA also increased the mRNA and protein levels of this enzyme. In addition, following 2 h exposure of the astrocytes to 10 micromol/L HupA, there was a significant up-regulation of mRNA for NGF and P75 low-affinity NGF receptor. The protein level of NGF was also increased after 24 h treatment with HupA. Our findings demonstrate for the first time that HupA has a direct or indirect neurotrophic activity, which might be beneficial in treatment of neurodegenerative disorders such as Alzheimer disease.

  9. A Loss-of-Function Screen for Phosphatases that Regulate Neurite Outgrowth Identifies PTPN12 as a Negative Regulator of TrkB Tyrosine Phosphorylation

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Dubreuil, Véronique; Miozzo, Federico

    2013-01-01

    Alterations in function of the neurotrophin BDNF are associated with neurodegeneration, cognitive decline, and psychiatric disorders. BDNF promotes axonal outgrowth and branching, regulates dendritic tree morphology and is important for axonal regeneration after injury, responses that largely....... This approach identified phosphatases from diverse families, which either positively or negatively modulate BDNF-TrkB-mediated neurite outgrowth, and most of which have little or no previously established function related to NT signaling. "Classical" protein tyrosine phosphatases (PTPs) accounted for 13......% of the candidate regulatory phosphatases. The top classical PTP identified as a negative regulator of BDNF-TrkB-mediated neurite outgrowth was PTPN12 (also called PTP-PEST). Validation and follow-up studies showed that endogenous PTPN12 antagonizes tyrosine phosphorylation of TrkB itself, and the downstream...

  10. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    Science.gov (United States)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  11. Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling.

    Science.gov (United States)

    Zhao, Lu; Feng, Yi; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi

    2016-12-01

    Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm 2 , 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm 2 ) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd 3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  12. BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates neurite development via PI3K-AKT and ERK signaling pathways.

    Science.gov (United States)

    Zhou, C; Li, C; Li, D; Wang, Y; Shao, W; You, Y; Peng, J; Zhang, X; Lu, L; Shen, X

    2013-12-19

    The elongation of neuron is highly dependent on membrane trafficking. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange protein 1 (BIG1) functions in the membrane trafficking between the Golgi apparatus and the plasma membrane. BFA, an uncompetitive inhibitor of BIG1 can inhibit neurite outgrowth and polarity development. In this study, we aimed to define the possible role of BIG1 in neurite development and to further investigate the potential mechanism. By immunostaining, we found that BIG1 was extensively colocalized with synaptophysin, a marker for synaptic vesicles in soma and partly in neurites. The amount of both protein and mRNA of BIG1 were up-regulated during rat brain development. BIG1 depletion significantly decreased the neurite length and inhibited the phosphorylation of phosphatidylinositide 3-kinase (PI3K) and protein kinase B (AKT). Inhibition of BIG1 guanine nucleotide-exchange factor (GEF) activity by BFA or overexpression of the dominant-negative BIG1 reduced PI3K and AKT phosphorylation, indicating regulatory effects of BIG1 on PI3K-AKT signaling pathway is dependent on its GEF activity. BIG1 siRNA or BFA treatment also significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation. Overexpression of wild-type BIG1 significantly increased ERK phosphorylation, but the dominant-negative BIG1 had no effect on ERK phosphorylation, indicating the involvement of BIG1 in ERK signaling regulation may not be dependent on its GEF activity. Our result identified a novel function of BIG1 in neurite development. The newly recognized function integrates the function of BIG1 in membrane trafficking with the activation of PI3K-AKT and ERK signaling pathways which are critical in neurite development. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1ß and activation of fibroblast growth factor receptor-1

    DEFF Research Database (Denmark)

    Gjørlund, Michelle D; Nielsen, Janne; Pankratova, Stanislava

    2012-01-01

    Neurexin-1 (NRXN1) and neuroligin-1 (NLGN1) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses and mediate signaling across the synapse, which modulates synaptic activity and determines the properties of neuronal networks. Defects in the genes encoding NLGN1...... have been linked to cognitive diseases such as autism. The roles of both NRXN1 and NLGN1 during synaptogenesis have been studied extensively, but little is known about the role of these molecules in neuritogenesis, which eventually results in neuronal circuitry formation. The present study investigated...... the neuritogenic effect of NLGN1 in cultures of hippocampal neurons. Our results show that NLGN1, both in soluble and membrane-bound forms, induces neurite outgrowth that depends on the interaction with NRXN1ß and on activation of fibroblast growth factor receptor-1. In addition, we demonstrate that a synthetic...

  14. DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.

    Science.gov (United States)

    Zaim, Merve; Isik, Sevim

    2018-04-25

    DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.

  15. Ecdysone signaling regulates specification of neurons with a male-specific neurite in Drosophila

    Directory of Open Access Journals (Sweden)

    Binglong Zhang

    2018-02-01

    Full Text Available Some mAL neurons in the male brain form the ipsilateral neurite (ILN[+] in a manner dependent on FruBM, a male-specific transcription factor. FruBM represses robo1 transcription, allowing the ILN to form. We found that the proportion of ILN[+]-mALs in all observed single cell clones dropped from ∼90% to ∼30% by changing the heat-shock timing for clone induction from 4-5 days after egg laying (AEL to 6-7 days AEL, suggesting that the ILN[+]-mALs are produced predominantly by young neuroblasts. Upon EcR-A knockdown, ILN[+]-mALs were produced at a high rate (∼60%, even when heat shocked at 6-7 days AEL, yet EcR-B1 knockdown reduced the proportion of ILN[+]-mALs to ∼30%. Immunoprecipitation assays in S2 cells demonstrated that EcR-A and EcR-B1 form a complex with FruBM. robo1 reporter transcription was repressed by FruBM and ecdysone counteracted FruBM. We suggest that ecdysone signaling modulates the FruBM action to produce an appropriate number of male-type neurons.

  16. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2

    Directory of Open Access Journals (Sweden)

    Yunjia Zhang

    2016-06-01

    Full Text Available ABSTRACT MicroRNAs (miRNAs are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

  17. Role of G protein-regulated inducer of neurite outgrowth 3 (GRIN3) in β-arrestin 2-Akt signaling and dopaminergic behaviors.

    Science.gov (United States)

    Mototani, Yasumasa; Okamura, Tadashi; Goto, Motohito; Shimizu, Yukiko; Yanobu-Takanashi, Rieko; Ito, Aiko; Kawamura, Naoya; Yagisawa, Yuka; Umeki, Daisuke; Nariyama, Megumi; Suita, Kenji; Ohnuki, Yoshiki; Shiozawa, Kouichi; Sahara, Yoshinori; Kozasa, Tohru; Saeki, Yasutake; Okumura, Satoshi

    2018-06-01

    The G protein-regulated inducer of neurite growth (GRIN) family has three isoforms (GRIN1-3), which bind to the Gαi/o subfamily of G protein that mediate signal processing via G protein-coupled receptors (GPCRs). Here, we show that GRIN3 is involved in regulation of dopamine-dependent behaviors and is essential for activation of the dopamine receptors (DAR)-β-arrestin signaling cascade. Analysis of functional regions of GRIN3 showed that a di-cysteine motif (Cys751/752) is required for plasma membrane localization. GRIN3 was co-immunoprecipitated with GPCR kinases 2/6 and β-arrestins 1/2. Among GRINs, only GRIN3, which is highly expressed in striatum, strongly interacted with β-arrestin 2. We also generated GRIN3-knockout mice (GRIN3KO). GRIN3KO exhibited reduced locomotor activity and increased anxiety-like behavior in the elevated maze test, as well as a reduced locomoter response to dopamine stimulation. We also examined the phosphorylation of Akt at threonine 308 (phospho308-Akt), which is dephosphorylated via a β-arrestin 2-mediated pathway. Dephosphorylation of phospho308-Akt via the D2R-β-arrestin 2 signaling pathway was completely abolished in striatum of GRIN3KO. Our results suggest that GRIN3 has a role in recruitment and assembly of proteins involved in β-arrestin-dependent, G protein-independent signaling.

  18. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13.

    Science.gov (United States)

    Scherer, Stephanie L; Cain, Matthew D; Kanai, Stanley M; Kaltenbronn, Kevin M; Blumer, Kendall J

    2017-06-16

    The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ 5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G i/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G i/o signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα 13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα 13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα 13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα 13 ·R7-RGS complexes. Because Gα 13 /R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ 5 with or without R7BP. We found that neurite retraction evoked by Gα 12/13 -dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα 12/13 but not Gα i/o These findings provide the first evidence that R7-RGS heterotrimers interact with Gα 13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by

  19. The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells

    OpenAIRE

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expressio...

  20. Signaling mechanisms of neurite outgrowth induced by the cell adhesion molecules NCAM and N-cadherin

    DEFF Research Database (Denmark)

    Hansen, S M; Berezin, V; Bock, E

    2008-01-01

    Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact with the surro......Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact...... extracellular guidance cues to intracellular events and thereby regulating neurite outgrowth. In this review, we focus on two CAMs, the neural cell adhesion molecule (NCAM) and N-cadherin, and their ability to mediate signaling associated with a neurite outgrowth response. In particular, we will focus on direct...

  1. Extremely Low-Frequency Electromagnetic Fields Promote In Vitro Neuronal Differentiation and Neurite Outgrowth of Embryonic Neural Stem Cells via Up-Regulating TRPC1

    Science.gov (United States)

    Ma, Qinlong; Chen, Chunhai; Deng, Ping; Zhu, Gang; Lin, Min; Zhang, Lei; Xu, Shangcheng; He, Mindi; Lu, Yonghui; Duan, Weixia; Pi, Huifeng; Cao, Zhengwang; Pei, Liping; Li, Min; Liu, Chuan; Zhang, Yanwen; Zhong, Min; Zhou, Zhou; Yu, Zhengping

    2016-01-01

    Exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) can enhance hippocampal neurogenesis in adult mice. However, little is focused on the effects of ELF-EMFs on embryonic neurogenesis. Here, we studied the potential effects of ELF-EMFs on embryonic neural stem cells (eNSCs). We exposed eNSCs to ELF-EMF (50 Hz, 1 mT) for 1, 2, and 3 days with 4 hours per day. We found that eNSC proliferation and maintenance were significantly enhanced after ELF-EMF exposure in proliferation medium. ELF-EMF exposure increased the ratio of differentiated neurons and promoted the neurite outgrowth of eNSC-derived neurons without influencing astrocyes differentiation and the cell apoptosis. In addition, the expression of the proneural genes, NeuroD and Ngn1, which are crucial for neuronal differentiation and neurite outgrowth, was increased after ELF-EMF exposure. Moreover, the expression of transient receptor potential canonical 1 (TRPC1) was significantly up-regulated accompanied by increased the peak amplitude of intracellular calcium level induced by ELF-EMF. Furthermore, silencing TRPC1 expression eliminated the up-regulation of the proneural genes and the promotion of neuronal differentiation and neurite outgrowth induced by ELF-EMF. These results suggest that ELF-EMF exposure promotes the neuronal differentiation and neurite outgrowth of eNSCs via up-regulation the expression of TRPC1 and proneural genes (NeuroD and Ngn1). These findings also provide new insights in understanding the effects of ELF-EMF exposure on embryonic brain development. PMID:26950212

  2. The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells

    Science.gov (United States)

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA’s effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes. PMID:23119107

  3. The protection of acetylcholinesterase inhibitor on β-amyloid-induced the injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells.

    Science.gov (United States)

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA's effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes.

  4. Neurite outgrowth induced by a synthetic peptide ligand of neural cell adhesion molecule requires fibroblast growth factor receptor activation

    DEFF Research Database (Denmark)

    Rønn, L C; Doherty, P; Holm, A

    2000-01-01

    identified a neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg) module of NCAM using a combinatorial library of synthetic peptides. Here we investigate whether stimulation of neurite outgrowth by this synthetic ligand of NCAM involves FGFRs. In primary cultures of cerebellar neurons...... from wild-type mice, the C3 peptide stimulated neurite outgrowth. This response was virtually absent in cultures of cerebellar neurons from transgenic mice expressing a dominant-negative form of the FGFR1. Likewise, in PC12E2 cells transiently expressing a dominant-negative form of the mouse FGFR1...

  5. Wnt5a regulates midbrain dopaminergic axon growth and guidance.

    Directory of Open Access Journals (Sweden)

    Brette D Blakely

    2011-03-01

    Full Text Available During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM the cues that guide dopaminergic (DA axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway. Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.

  6. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    Science.gov (United States)

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Actin Waves Do Not Boost Neurite Outgrowth in the Early Stages of Neuron Maturation

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    Simone Mortal

    2017-12-01

    Full Text Available During neurite development, Actin Waves (AWs emerge at the neurite base and move up to its tip, causing a transient retraction of the Growth Cone (GC. Many studies have shown that AWs are linked to outbursts of neurite growth and, therefore, contribute to the fast elongation of the nascent axon. Using long term live cell-imaging, we show that AWs do not boost neurite outgrowth and that neurites without AWs can elongate for several hundred microns. Inhibition of Myosin II abolishes the transient GC retraction and strongly modifies the AWs morphology. Super-resolution nanoscopy shows that Myosin IIB shapes the growth cone-like AWs structure and is differently distributed in AWs and GCs. Interestingly, depletion of membrane cholesterol and inhibition of Rho GTPases decrease AWs frequency and velocity. Our results indicate that Myosin IIB, membrane tension, and small Rho GTPases are important players in the regulation of the AW dynamics. Finally, we suggest a role for AWs in maintaining the GCs active during environmental exploration.

  8. Electricity regulation and economic growth

    OpenAIRE

    Costa, M. Teresa (Maria Teresa), 1951-; Garcia-Quevedo, Jose; Trujillo-Baute, Elisa

    2018-01-01

    The main objective of this paper is to analyse the effect of electricity regulation on economic growth. Although the relationship between electricity consumption and economic growth has been extensively analysed in the empirical literature, this framework has not been used to estimate the effect of electricity regulation on economic growth. Understanding this effect is essential for the assessment of regulatory policy. Specifically, we assess the effects of two major areas of regulation, rene...

  9. Endothelin-2/Vasoactive Intestinal Contractor: Regulation of Expression via Reactive Oxygen Species Induced by CoCl22, and Biological Activities Including Neurite Outgrowth in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2006-01-01

    Full Text Available This paper reviews the local hormone endothelin-2 (ET-2, or vasoactive intestinal contractor (VIC, a member of the vasoconstrictor ET peptide family, where ET-2 is the human orthologous peptide of the murine VIC. While ET-2/VIC gene expression has been observed in some normal tissues, ET-2 recently has been reported to act as a tumor marker and as a hypoxia-induced autocrine survival factor in tumor cells. A recently published study reported that the hypoxic mimetic agent CoCl2 at 200 µM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced intracellular reactive oxygen species (ROS increase and neurite outgrowth in neuronal model PC12 cells. The ROS was generated by addition of CoCl2 to the culture medium, and the CoCl2-induced effects were completely inhibited by the antioxidant N-acetyl cysteine. Furthermore, interleukin-6 (IL-6 gene expression was up-regulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by CoCl2-induced ROS may be associated with neuronal differentiation through the regulation of IL-6 expression. CoCl2 acts as a pro-oxidant, as do Fe(II, III and Cu(II. However, some biological activities have been reported for CoCl2 that have not been observed for other metal salts such as FeCl3, CuSO4, and NiCl2. The characteristic actions of CoCl2 may be associated with the differentiation of PC12 cells. Further elucidation of the mechanism of neurite outgrowth and regulation of ET-2/VIC expression by CoCl2 may lead to the development of treatments for neuronal disorders.

  10. First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

    Science.gov (United States)

    Kucher, Klaus; Johns, Donald; Maier, Doris; Abel, Rainer; Badke, Andreas; Baron, Hagen; Thietje, Roland; Casha, Steven; Meindl, Renate; Gomez-Mancilla, Baltazar; Pfister, Christian; Rupp, Rüdiger; Weidner, Norbert; Mir, Anis; Schwab, Martin E; Curt, Armin

    2018-05-01

    Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

  11. DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

    Science.gov (United States)

    Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

    2015-01-01

    In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

  12. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, K; Sato, C; Shimizu, N [Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Ora-gun, Gunma 374-0193 (Japan); Naka, Y [Bio-Nano Electronics Research Center, Toyo University, 2100 Kujirai, Kawagoe-shi, Saitama 350-8585 (Japan); Whitby, R, E-mail: shimizu@toyonet.toyo.ac.jp [School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockroft Building, Lewes Road, Brighton BN2 4GJ (United Kingdom)

    2010-03-19

    Low concentrations (0.11-1.7 {mu}g ml{sup -1}) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 {mu}g ml{sup -1} CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

  13. Hydrogel Design for Supporting Neurite Outgrowth and Promoting Gene Delivery to Maximize Neurite Extension

    Science.gov (United States)

    Shepard, Jaclyn A.; Stevans, Alyson C.; Holland, Samantha; Wang, Christine E.; Shikanov, Ariella; Shea, Lonnie D.

    2012-01-01

    Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration. PMID:22038654

  14. The functionalized amino acid (S-Lacosamide subverts CRMP2-mediated tubulin polymerization to prevent constitutive and activity-dependent increase in neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Sarah M Wilson

    2014-07-01

    Full Text Available Activity-dependent neurite outgrowth is a highly complex, regulated process with important implications for neuronal circuit remodeling in development as well as in seizure-induced sprouting in epilepsy. Recent work has linked outgrowth to collapsin response mediator protein 2 (CRMP2, an intracellular phosphoprotein originally identified as axon guidance and growth cone collapse protein. The neurite outgrowth promoting function of CRMP2 is regulated by its phosphorylation state. In this study, depolarization (potassium chloride-driven activity increased the level of active CRMP2 by decreasing its phosphorylation by GSK3β via a reduction in priming by Cdk5. To determine the contribution of CRMP2 in activity-driven neurite outgrowth, we screened a limited set of compounds for their ability to reduce neurite outgrowth but not modify voltage-gated sodium channel (VGSC biophysical properties. This led to the identification of (S-lacosamide ((S-LCM, a stereoisomer of the clinically used antiepileptic drug (R-LCM (Vimpat®, as a novel tool for preferentially targeting CRMP2-mediated neurite outgrowth. Whereas (S-LCM was ineffective in targeting VGSCs, the presumptive pharmacological targets of (R-LCM, (S-LCM was more efficient than (R-LCM in subverting neurite outgrowth. Biomolecular interaction analyses revealed that (S-LCM bound to wildtype CRMP2 with low micromolar affinity, similar to (R-LCM. Through the use of this novel tool, the activity-dependent increase in neurite outgrowth observed following depolarization was characterized to be reliant on CRMP2 function. Knockdown of CRMP2 by siRNA in cortical neurons resulted in reduced CRMP2-dependent neurite outgrowth; incubation with (S-LCM phenocopied this effect. Other CRMP2-mediated processes were unaffected. (S-LCM subverted neurite outgrowth not by affecting the canonical CRMP2-tubulin association but rather by impairing the ability of CRMP2 to promote tubulin polymerization, events that are

  15. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  16. Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

    Science.gov (United States)

    Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

    2012-01-01

    The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

  17. Morphological identification and development of neurite in Drosophila ventral nerve cord neuropil.

    Directory of Open Access Journals (Sweden)

    Guangming Gan

    Full Text Available In Drosophila, ventral nerve cord (VNC occupies most of the larval central nervous system (CNS. However, there is little literature elaborating upon the specific types and growth of neurites as defined by their structural appearance in Drosophila larval VNC neuropil. Here we report the ultrastructural development of different types VNC neurites in ten selected time points in embryonic and larval stages utilizing transmission electron microscopy. There are four types of axonal neurites as classified by the type of vesicular content: clear vesicle (CV neurites have clear vesicles and some T-bar structures; Dense-core vesicle (DV neurites have dense-core vesicles and without T-bar structures; Mixed vesicle (MV neurites have mixed vesicles and some T-bar structures; Large vesicle (LV neurites are dominated by large, translucent spherical vesicles but rarely display T-bar structures. We found dramatic remodeling in CV neurites which can be divided into five developmental phases. The neurite is vacuolated in primary (P phase, they have mitochondria, microtubules or big dark vesicles in the second (S phase, and they contain immature synaptic features in the third (T phase. The subsequent bifurcate (B phase appears to undergo major remodeling with the appearance of the bifurcation or dendritic growth. In the final mature (M phase, high density of commensurate synaptic vesicles are distributed around T-bar structures. There are four kinds of morphological elaboration of the CVI neurite sub-types. First, new neurite produces at the end of axon. Second, new neurite bubbles along the axon. Third, the preexisting neurite buds and develops into several neurites. The last, the bundled axons form irregularly shape neurites. Most CVI neurites in M phase have about 1.5-3 µm diameter, they could be suitable to analyze their morphology and subcellular localization of specific proteins by light microscopy, and they could serve as a potential model in CNS in vivo

  18. Morphological identification and development of neurite in Drosophila ventral nerve cord neuropil.

    Science.gov (United States)

    Gan, Guangming; Lv, Huihui; Xie, Wei

    2014-01-01

    In Drosophila, ventral nerve cord (VNC) occupies most of the larval central nervous system (CNS). However, there is little literature elaborating upon the specific types and growth of neurites as defined by their structural appearance in Drosophila larval VNC neuropil. Here we report the ultrastructural development of different types VNC neurites in ten selected time points in embryonic and larval stages utilizing transmission electron microscopy. There are four types of axonal neurites as classified by the type of vesicular content: clear vesicle (CV) neurites have clear vesicles and some T-bar structures; Dense-core vesicle (DV) neurites have dense-core vesicles and without T-bar structures; Mixed vesicle (MV) neurites have mixed vesicles and some T-bar structures; Large vesicle (LV) neurites are dominated by large, translucent spherical vesicles but rarely display T-bar structures. We found dramatic remodeling in CV neurites which can be divided into five developmental phases. The neurite is vacuolated in primary (P) phase, they have mitochondria, microtubules or big dark vesicles in the second (S) phase, and they contain immature synaptic features in the third (T) phase. The subsequent bifurcate (B) phase appears to undergo major remodeling with the appearance of the bifurcation or dendritic growth. In the final mature (M) phase, high density of commensurate synaptic vesicles are distributed around T-bar structures. There are four kinds of morphological elaboration of the CVI neurite sub-types. First, new neurite produces at the end of axon. Second, new neurite bubbles along the axon. Third, the preexisting neurite buds and develops into several neurites. The last, the bundled axons form irregularly shape neurites. Most CVI neurites in M phase have about 1.5-3 µm diameter, they could be suitable to analyze their morphology and subcellular localization of specific proteins by light microscopy, and they could serve as a potential model in CNS in vivo development.

  19. Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-11-01

    Full Text Available Background/Aims: Migration of Schwann cells (SCs progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs are two central events during the development of the peripheral nervous system (PNS. How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

  20. Tax and Semaphorin 4D Released from Lymphocytes Infected with Human Lymphotropic Virus Type 1 and Their Effect on Neurite Growth.

    Science.gov (United States)

    Quintremil, Sebastián; Alberti, Carolina; Rivera, Matías; Medina, Fernando; Puente, Javier; Cartier, Luis; Ramírez, Eugenio; Tanaka, Yuetsu; Valenzuela, M Antonieta

    2016-01-01

    Human lymphotropic virus type 1 (HTLV-1) is a retrovirus causing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurodegenerative central nervous system (CNS) axonopathy. This virus mainly infects CD4(+) T lymphocytes without evidence of neuronal infection. Viral Tax, secreted from infected lymphocytes infiltrated in the CNS, is proposed to alter intracellular pathways related to axonal cytoskeleton dynamics, producing neurological damage. Previous reports showed a higher proteolytic release of soluble Semaphorin 4D (sSEMA-4D) from CD4(+) T cells infected with HTLV-1. Soluble SEMA-4D binds to its receptor Plexin-B1, activating axonal growth collapse pathways in the CNS. In the current study, an increase was found in both SEMA-4D in CD4(+) T cells and sSEMA-4D released to the culture medium of peripheral blood mononuclear cells (PBMCs) from HAM/TSP patients compared to asymptomatic carriers and healthy donors. After a 16-h culture, infected PBMCs showed significantly higher levels of CRMP-2 phosphorylated at Ser(522). The effect was blocked either with anti-Tax or anti-SEMA-4D antibodies. The interaction of Tax and sSEMA-4D was found in secreted medium of PBMCs in patients, which might be associated with a leading role of Tax with the SEMA-4D-Plexin-B1 signaling pathway. In infected PBMCs, the migratory response after transwell assay showed that sSEMA-4D responding cells were CD4(+)Tax(+) T cells with a high CRMP-2 pSer(522) content. In the present study, the participation of Tax-sSEMA-4D in the reduction in neurite growth in PC12 cells produced by MT2 (HTLV-1-infected cell line) culture medium was observed. These results lead to the participation of plexins in the reported effects of infected lymphocytes on neuronal cells.

  1. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity

    International Nuclear Information System (INIS)

    Dey, Nandini; Howell, Brian W.; De, Pradip K.; Durden, Donald L.

    2005-01-01

    Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation

  2. Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

    Science.gov (United States)

    Jin, Ying; Sui, Hai-juan; Dong, Yan; Ding, Qi; Qu, Wen-hui; Yu, Sheng-xue; Jin, Ying-xin

    2012-01-01

    Aim: To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. Methods: Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05–10 μmol/L) for various lengths of time. For pharmacological experiments, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Digital images of neurons were analyzed for total neurite branch length (TNBL), neurite number, terminal branch number, and soma area by SPOT Advanced Imaging software. After incubation with atorvastatin for 48 h, the levels of phosphorylated 3-phosphoinoside-dependent protein kinase-1 (PDK1), phospho-Akt, phosphorylated mammalian target of rapamycin (mTOR), phosphorylated 4E-binding protein 1 (4E-BP1), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in the cortical neurons were evaluated using Western blotting analyses. Results: Atorvastatin (0.05–10 μmol/L) resulted in dose-dependent increase in neurite number and length in these neurons. Pretreatment of the cortical neurons with phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 (30 μmol/L) and wortmannin (5 μmol/L), Akt inhibitor tricribine (1 μmol/L) or mTOR inhibitor rapamycin (100 nmol/L) blocked the atorvastatin-induced increase in neurite outgrowth, suggesting that atorvastatin promoted neurite outgrowth via activating the PI3K/Akt/mTOR signaling pathway. Atorvastatin (10 μmol/L) significantly increased the levels of phosphorylated PDK1, Akt and mTOR in the cortical neurons, which were prevented by LY294002 (30 μmol/L). Moreover, atorvastatin (10 μmol/L) stimulated the phosphorylation of 4E-BP1 and p70S6K, the substrates of mTOR, in the cortical neurons. In addition, atorvastatin (10 μmol/L) significantly increased the phosphorylated GSK-3β level in the cortical

  3. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    Directory of Open Access Journals (Sweden)

    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  4. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration.

    Science.gov (United States)

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-12-15

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7-21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy.

  5. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration☆

    Science.gov (United States)

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-01-01

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

  6. Chemoenzymatically prepared konjac ceramide inhibits NGF-induced neurite outgrowth by a semaphorin 3A-like action

    Directory of Open Access Journals (Sweden)

    Seigo Usuki

    2016-03-01

    Full Text Available Dietary sphingolipids such as glucosylceramide (GlcCer are potential nutritional factors associated with prevention of metabolic syndrome. Our current understanding is that dietary GlcCer is degraded to ceramide and further metabolized to sphingoid bases in the intestine. However, ceramide is only found in trace amounts in food plants and thus is frequently taken as GlcCer in a health supplement. In the present study, we successfully prepared konjac ceramide (kCer using endoglycoceramidase I (EGCase I. Konjac, a plant tuber, is an enriched source of GlcCer (kGlcCer, and has been commercialized as a dietary supplement to improve dry skin and itching that are caused by a deficiency of epidermal ceramide. Nerve growth factor (NGF produced by skin cells is one of the itch factors in the stratum corneum of the skin. Semaphorin 3A (Sema 3A has been known to inhibit NGF-induced neurite outgrowth of epidermal nerve fibers. It is well known that the itch sensation is regulated by the balance between NGF and Sema 3A. In the present study, while kGlcCer did not show an in vitro inhibitory effect on NGF-induced neurite outgrowth of PC12 cells, kCer was demonstrated to inhibit a remarkable neurite outgrowth. In addition, the effect of kCer was similar to that of Sema 3A in cell morphological changes and neurite retractions, but different from C2-Ceramide. kCer showed a Sema 3A-like action, causing CRMP2 phosphorylation, which results in a collapse of neurite growth cones. Thus, it is expected that kCer is an advanced konjac ceramide material that may have neurite outgrowth-specific action to relieve uncontrolled and serious itching, in particular, from atopic eczema.

  7. Electric field-induced astrocyte alignment directs neurite outgrowth.

    Science.gov (United States)

    Alexander, John K; Fuss, Babette; Colello, Raymond J

    2006-05-01

    The extension and directionality of neurite outgrowth are key to achieving successful target connections during both CNS development and during the re-establishment of connections lost after neural trauma. The degree of axonal elongation depends, in large part, on the spatial arrangement of astrocytic processes rich in growth-promoting proteins. Because astrocytes in culture align their processes on exposure to an electrical field of physiological strength, we sought to determine the extent to which aligned astrocytes affect neurite outgrowth. To this end, dorsal root ganglia cells were seeded onto cultured rat astrocytes that were pre-aligned by exposure to an electric field of physiological strength (500 mV mm(-1)). Using confocal microscopy and digital image analysis, we found that neurite outgrowth at 24 hours and at 48 hours is enhanced significantly and directed consistently along the aligned astrocyte processes. Moreover, this directed neurite outgrowth is maintained when grown on fixed, aligned astrocytes. Collectively, these results indicate that endogenous electric fields present within the developing CNS might act to align astrocyte processes, which can promote and direct neurite growth. Furthermore, these results demonstrate a simple method to produce an aligned cellular substrate, which might be used to direct regenerating neurites.

  8. Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling.

    Science.gov (United States)

    Tian, Xiaoxia; Yan, Huijuan; Li, Jiayi; Wu, Shuang; Wang, Junyu; Fan, Lifei

    2017-01-13

    Members of the well-known semaphorin family of proteins can induce both repulsive and attractive signaling in neural network formation and their cytoskeletal effects are mediated in part by small guanosine 5'-triphosphatase (GTPases). The aim of this study was to investigate the cellular role of Rif GTPase in the neurotrophin-induced neurite outgrowth. By using PC12 cells which are known to cease dividing and begin to show neurite outgrowth responding to nerve growth factor (NGF), we found that semaphorin 6A was as effective as nerve growth factor at stimulating neurite outgrowth in PC12 cells, and that its neurotrophic effect was transmitted through signaling by mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K). We further found that neurotrophin-induced neurite formation in PC12 cells could be partially mediated by inhibition of Rif GTPase activity downstream of MAPKs and PI3K signaling. In conclusion, we newly identified Rif as a regulator of the cytoskeletal rearrangement mediated by semaphorins.

  9. Vital role of protein kinase C-related kinase (PRK1) in the formation and stability of neurites during hypoxia

    OpenAIRE

    Thauerer, Bettina; zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

    2010-01-01

    Exposure of pheochromocytoma (PC12) cells to hypoxia (1% O2) favors differentiation at the expense of cell viability. Additional incubation with nerve growth factor (NGF) and guanosine, a purine nucleoside with neurotrophin characteristics, rescued cell viability and further enhanced the extension of neurites. In parallel, an increase in the activity of protein kinase C-related kinase (PRK1), which is known to be involved in regulation of the actin cytoskeleton, was observed in hypoxic cells....

  10. Regulators of growth plate maturation

    NARCIS (Netherlands)

    Emons, Joyce Adriana Mathilde

    2010-01-01

    Estrogen is known to play an important role in longitudinal bone growth and growth plate maturation, but the mechanism by which estrogens exert their effect is not fully understood. In this thesis this role is further explored. Chapter 1 contains a general introduction to longitudinal bone growth

  11. Stringency of environmental regulation and aquaculture growth

    DEFF Research Database (Denmark)

    Gedefaw Abate, Tenaw; Nielsen, Rasmus; Tveterås, Ragnar

    2016-01-01

    remarkable growth in aquaculture while others have stagnated or even declined have not been determined. In this article, we investigate whether environmental regulations have an impact on aquaculture growth. Using a cross-country regression analysis, we show that stringent environmental regulations......During the last three decades, aquaculture has been the fastest growing animal-food-producing sector in the world, accounting for half of the present seafood supply. However, there is a significant growth disparity among aquaculture-producing countries. The reasons why some countries have achieved...... are negatively related to aquaculture growth, whereas GDP growth has a positive effect. Countries often face a difficult balancing act between growth and environmental considerations when devising regulations. Our empirical results suggest that stricter environmental regulations in developed countries have...

  12. Chemical Growth Regulators for Guayule Plants

    Science.gov (United States)

    Dastoor, M. N.; Schubert, W. W.; Petersen, G. R.

    1982-01-01

    Test Tubes containing Guayule - tissue cultures were used in experiments to test effects of chemical-growth regulators. The shoots grew in response to addition of 2-(3,4-dichlorophenoxy)-triethylamine (triethylamine (TEA) derivative) to agar medium. Preliminary results indicate that a class of compounds that promotes growth in soil may also promote growth in a culture medium. Further experiments are needed to define the effect of the TEA derivative.

  13. The output of neuronotrophic and neurite-promoting agents from rat brain astroglial cells: a microculture method for screening potential regulatory molecules.

    Science.gov (United States)

    Rudge, J S; Manthorpe, M; Varon, S

    1985-04-01

    Throughout embryonic development, as well as in response to injury of the central nervous system, astroglial cells may present neurons with a critical supply of neuronotrophic and neurite-promoting factors which control, respectively, neuronal survival and axonal growth. The identification of such astroglial cell-derived factors, as well as of specific extrinsic agents regulating their production, will require the use of in vitro techniques. We define here a new microculture system in which added agents can be screened for their ability to enhance or inhibit the output of trophic and neurite-promoting factors from purified neonatal rat brain astroglial cells. With such a procedure, thousands of replicate secondary astroglial cultures can be set-up and maintained in chemically defined medium, on a defined substratum and in a viable, low proliferative stable state. These cultured astroglial cells release into their medium at least three distinct and separable types of agents addressing nerve cells in vitro: (i) high molecular weight trophic factors (Mr greater than 10,000) which support the survival of embryonic peripheral neurons; (ii) low molecular weight trophic agents (Mr less than 10,000) supporting embryonic central neurons; and (iii) polyornithine-binding neurite-promoting factors which enhance neuritic regeneration for both peripheral and central neurons. The temporal release patterns of these three agents from astroglial cultures are quite distinct suggesting that their output is independently regulated.

  14. Synthesis and application of labelled growth regulators

    International Nuclear Information System (INIS)

    Shyutte, G.R.

    1982-01-01

    For the investigation of the metabolism both of phytoeffectors like herbicides and plant growth regulators such compounds are needed in radioactive labelled form. The synthesis of radioactive labelled fluorodifen, nitrofen, ethephon, diphenylic acetic acid, 2,4-dichlorophenoxyisobutyric acid, abscisic acid, hydroxybenzoic acids and different conjugates are described. Some examples of these compounds metabolism in plants are discussed [ru

  15. Non-cytotoxic Concentration of Cisplatin Decreases Neuroplasticity-Related Proteins and Neurite Outgrowth Without Affecting the Expression of NGF in PC12 Cells.

    Science.gov (United States)

    Ferreira, Rafaela Scalco; Dos Santos, Neife Aparecida Guinaim; Martins, Nádia Maria; Fernandes, Laís Silva; Dos Santos, Antonio Cardozo

    2016-11-01

    Cisplatin is the most effective and neurotoxic platinum chemotherapeutic agent. It induces a peripheral neuropathy characterized by distal axonal degeneration that might progress to degeneration of cell bodies and apoptosis. Most symptoms occur nearby distal axonal branches and axonal degeneration might induce peripheral neuropathy regardless neuronal apoptosis. The toxic mechanism of cisplatin has been mainly associated with DNA damage, but cisplatin might also affect neurite outgrowth. Nevertheless, the neurotoxic mechanism of cisplatin remains unclear. We investigated the early effects of cisplatin on axonal plasticity by using non-cytotoxic concentrations of cisplatin and PC12 cells as a model of neurite outgrowth and differentiation. PC12 cells express NGF-receptors (trkA) and respond to NGF by forming neurites, branches and synaptic vesicles. For comparison, we used a neuronal model (SH-SY5Y cells) that does not express trkA nor responds to NGF. Cisplatin did not change NGF expression in PC12 cells and decreased neurite outgrowth in both models, suggesting a NGF/trkA independent mechanism. It also reduced axonal growth (GAP-43) and synaptic (synapsin I and synaptophysin) proteins in PC12 cells, without inducing mitochondrial damage or apoptosis. Therefore, cisplatin might affect axonal plasticity before DNA damage, NGF/trkA down-regulation, mitochondrial damage or neuronal apoptosis. This is the first study to show that neuroplasticity-related proteins might be early targets of the neurotoxic action of cisplatin and their role on cisplatin-induced peripheral neuropathy should be investigated in vivo.

  16. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  17. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    International Nuclear Information System (INIS)

    Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

    2013-01-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H 2 O 2 neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS production and

  18. Microelectrode array-induced neuronal alignment directs neurite outgrowth: analysis using a fast Fourier transform (FFT).

    Science.gov (United States)

    Radotić, Viktorija; Braeken, Dries; Kovačić, Damir

    2017-12-01

    Many studies have shown that the topography of the substrate on which neurons are cultured can promote neuronal adhesion and guide neurite outgrowth in the same direction as the underlying topography. To investigate this effect, isotropic substrate-complementary metal-oxide-semiconductor (CMOS) chips were used as one example of microelectrode arrays (MEAs) for directing neurite growth of spiral ganglion neurons. Neurons were isolated from 5 to 7-day-old rat pups, cultured 1 day in vitro (DIV) and 4 DIV, and then fixed with 4% paraformaldehyde. For analysis of neurite alignment and orientation, fast Fourier transformation (FFT) was used. Results revealed that on the micro-patterned surface of a CMOS chip, neurons orient their neurites along three directional axes at 30, 90, and 150° and that neurites aligned in straight lines between adjacent pillars and mostly followed a single direction while occasionally branching perpendicularly. We conclude that the CMOS substrate guides neurites towards electrodes by means of their structured pillar organization and can produce electrical stimulation of aligned neurons as well as monitoring their neural activities once neurites are in the vicinity of electrodes. These findings are of particular interest for neural tissue engineering with the ultimate goal of developing a new generation of MEA essential for improved electrical stimulation of auditory neurons.

  19. Epigenetic regulation of axon and dendrite growth

    Directory of Open Access Journals (Sweden)

    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  20. Electric field-induced astrocyte alignment directs neurite outgrowth

    OpenAIRE

    ALEXANDER, JOHN K.; FUSS, BABETTE; COLELLO, RAYMOND J.

    2006-01-01

    The extension and directionality of neurite outgrowth are key to achieving successful target connections during both CNS development and during the re-establishment of connections lost after neural trauma. The degree of axonal elongation depends, in large part, on the spatial arrangement of astrocytic processes rich in growth-promoting proteins. Because astrocytes in culture align their processes on exposure to an electrical field of physiological strength, we sought to determine the extent t...

  1. Bifenthrin causes neurite retraction in the absence of cell death: a model for pesticide associated neurodegeneration.

    Science.gov (United States)

    Nandi, Avishek; Chandil, Daljit; Lechesal, Rethabile; Pryor, Stephen C; McLaughlin, Ashlea; Bonventre, Josephine A; Flynnx, Katherine; Weeks, Benjamin S

    2006-05-01

    Bifenthrin is a synthetic pyrethroid insecticide derivative of naturally occurring pyrethrins from chrysanthemum flowers. Bifenthrin is considered relatively safe and therefore incorporated as the active ingredient in preparations sold over the counter for household use. Recent studies have raised concern that chronic exposure to pesticides in the home setting may increase the risk for neurodegenerative diseases. To address this concer, in the present study, bifenthrin is added to pre-differentiated PC12 and effect of bifenthrin on the retraction of existing neurites is observed a model for neurodegeneration. PC12 cells were differentiated with nerve growth factor for twenty-four hours and then treated with what was determined to be a sublethal dose of bifenthrin for up to an additional 48 hours. The percent of cells with neurites was assessed at various times before and after nerve growth factor treatment. Bifenthrin toxicity was determined using trypan blue exclusion. Bifenthrin was not toxic to PC12 cells at concentrations ranging from 1 x 10(-10) M to 1 x 10(-4) M. Twenty-four hours after nerve growth factor treatment, a maximum percent of cells had formed neurites and with a treatment of 1 x 10(-5) M bifenthrin, approximately 80% of these neurites retracted in within 12 additional hours and almost all neurites had retracted within 48 hours. Trypan exclusion showed that these cells were viable. These data show that bifenthrin can stimulate the retraction of neurites in the absence of frank toxicity.

  2. Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

    Science.gov (United States)

    Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

    2014-01-01

    It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

  3. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    Directory of Open Access Journals (Sweden)

    Yi-sheng Li

    2016-01-01

    Full Text Available GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

  4. Bifenthrin inhibits neurite outgrowth in differentiating PC12 cells.

    Science.gov (United States)

    Tran, Van; Hoffman, Natalie; Mofunanaya, Adaobi; Pryor, Stephen C; Ojugbele, Olutosin; McLaughlin, Ashlea; Gibson, Lydia; Bonventre, Josephine A; Flynn, Katherine; Weeks, Benjamin S

    2006-02-01

    Bifenthrin is a third generation member of the synthetic pyrethroid family of insecticides. As a new pesticide within a relatively new class of pesticides, bifenthrin is considered relatively safe. Here, we used the PC12 neuronal cell line to examine the effect of bifenthrin on the formation of neurites and the potential developmental neurotoxicity of this pesticide. PC12 cells were exposed to varying concentrations of technical grade bifenthrin or Ortho Home Defense. Cell viability was determined using the AlmarBlue Toxicity Assay. Nontoxic concentrations of these chemicals were concomitantly with nerve growth factor and neurite outgrowth was assessed. Ortho Home Defense preparation reduced PC12 cell viability by approximately 50% and 70% at dilutions that correlate to bifenthrin concentrations of 10(-5) M and 10(-4) M, respectively. In contrast, technical grade bifenthrin, was not toxic to PC12 cells at 10(-3) M, which was the highest concentration tested that was soluble. At "nontoxic" concentrations of 10(-7) M and 10(-6) M, the Ortho Home Defense inhibited nerve growth factor-mediated neurite outgrowth by 30% and 55% respectively. Furthermore the nontoxic concentrations of technical grade bifenthrin of 10(-6) M and 10(-3) M inhibited neurite outgrowth by approximately 35% and 75% respectively. These data suggest that the toxicity of the Ortho Home Defense preparation was due to the "inert" additives in the preparation and not the bifenthrin itself. Further, these data suggest that, even in the absence of overt toxicity, bifenthrin may have deleterious effects to developing nervous system.

  5. Process for producing vegetative and tuber growth regulator

    Science.gov (United States)

    Stutte, Gary W. (Inventor); Yorio, Neil C. (Inventor)

    1999-01-01

    A process of making a vegetative and tuber growth regulator. The vegetative and tuber growth regulator is made by growing potato plants in a recirculating hydroponic system for a sufficient time to produce the growth regulator. Also, the use of the vegetative and growth regulator on solanaceous plants, tuber forming plants and ornamental seedlings by contacting the roots or shoots of the plant with a sufficient amount of the growth regulator to regulate the growth of the plant and one more of canopy size, plant height, stem length, internode number and presence of tubers in fresh mass. Finally, a method for regulating the growth of potato plants using a recirculating hydroponic system is described.

  6. Conversion Disorder Presenting As Neuritic Leprosy

    Directory of Open Access Journals (Sweden)

    Sayal SK

    2000-01-01

    Full Text Available Conversion disorder is not normally listed amongst the conditions in differential diagnosis of leprosy neuropathy. A case conversion reaction who was initially diagnosed as neuritic leprosy is reported. Patient responded to narcosuggestion and psychotherapy.

  7. Fibroblast Growth Factor Signaling in Metabolic Regulation.

    Science.gov (United States)

    Nies, Vera J M; Sancar, Gencer; Liu, Weilin; van Zutphen, Tim; Struik, Dicky; Yu, Ruth T; Atkins, Annette R; Evans, Ronald M; Jonker, Johan W; Downes, Michael Robert

    2015-01-01

    The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  8. A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells

    International Nuclear Information System (INIS)

    Sharma, Aarti; Lambrechts, Anja; Le thi Hao; Le, Thanh T.; Sewry, Caroline A.; Ampe, Christophe; Burghes, Arthur H.M.; Morris, Glenn E.

    2005-01-01

    Spinal muscular atrophy (SMA) is caused by reduced levels of SMN (survival of motor neurons protein) and consequent loss of motor neurons. SMN is involved in snRNP transport and nuclear RNA splicing, but axonal transport of SMN has also been shown to occur in motor neurons. SMN also binds to the small actin-binding protein, profilin. We now show that SMN and profilin II co-localise in the cytoplasm of differentiating rat PC12 cells and in neurite-like extensions, especially at their growth cones. Many components of known SMN complexes were also found in these extensions, including gemin2 (SIP-1), gemin6, gemin7 and unrip (unr-interacting protein). Coilin p80 and Sm core protein immunoreactivity, however, were seen only in the nucleus. SMN is known to associate with β-actin mRNA and specific hnRNPs in axons and in neurite extensions of cultured nerve cells, and SMN also stimulates neurite outgrowth in cultures. Our results are therefore consistent with SMN complexes, rather than SMN alone, being involved in the transport of actin mRNPs along the axon as in the transport of snRNPs into the nucleus by similar SMN complexes. Antisense knockdown of profilin I and II isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN and its associated proteins in cytoplasmic aggregates. BIAcore studies demonstrated a high affinity interaction of SMN with profilin IIa, the isoform present in developing neurons. Pathogenic missense mutations in SMN, or deletion of exons 5 and 7, prevented this interaction. The interaction is functional in that SMN can modulate actin polymerisation in vitro by reducing the inhibitory effect of profilin IIa. This suggests that reduced SMN in SMA might cause axonal pathfinding defects by disturbing the normal regulation of microfilament growth by profilins

  9. Fibroblast growth factor signaling in metabolic regulation

    Directory of Open Access Journals (Sweden)

    Vera eNies

    2016-01-01

    Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  10. miR-103 Promotes Neurite Outgrowth and Suppresses Cells Apoptosis by Targeting Prostaglandin-Endoperoxide Synthase 2 in Cellular Models of Alzheimer's Disease.

    Science.gov (United States)

    Yang, Hui; Wang, Hongcai; Shu, Yongwei; Li, Xuling

    2018-01-01

    miR-103 has been reported to be decreased in brain of transgenic mouse model of Alzheimer's disease (AD) and in cerebrospinal fluid (CSF) of AD patients, while the detailed mechanism of its effect on AD is obscure, thus this study aimed to investigate the effect of miR-103 expression on neurite outgrowth and cells apoptosis as well as its targets in cellular models of AD. Blank mimic (NC1-mimic), miR-103 mimic, blank inhibitor (NC2-mimic) and miR-103 inhibitor plasmids were transferred into PC12 cellular AD model and Cellular AD model of cerebral cortex neurons which were established by Aβ1-42 insult. Rescue experiment was subsequently performed by transferring Prostaglandin-endoperoxide synthase 2 (PTGS2) and miR-103 mimic plasmid. mRNA and protein expressions were detected by qPCR and Western Blot assays. Total neurite outgrowth was detected by microscope, cells apoptosis was determined by Hoechst/PI assay, and apoptotic markers Caspase 3 and p38 expressions were determined by Western Blot assay. In both PC12 and cerebral cortex neurons cellular AD models, miR-103 mimic increases the total neurite outgrowth compared with NC1-mimic, while miR-103 inhibitor decreases the total neurite outgrowth than NC2-inhibitor. The apoptosis rate was decreased in miR-103 mimic group than NC1-mimic group while increased in miR-103 inhibitor group than NC2-inhibitor group. PTGS2, Adisintegrin and metalloproteinase 10 (ADAM10) and neprilysin (NEP) were selected as target genes of miR-103 by bioinformatics analysis. And PTGS2 was found to be conversely regulated by miR-103 expression while ADAM10 and NEP were not affected. After transfection by PTGS2 and miR-103 mimic plasmid in PC12 cellular AD model, the total neurite growth was shortened compared with miR-103 mimic group, and cells apoptosis was enhanced which indicated PTGS2 mimic attenuated the influence of miR-103 mimic on progression of AD. In conclusion, miR-103 promotes total neurite outgrowth and inhibits cells apoptosis

  11. Slit2 inactivates GSK3β to signal neurite outgrowth inhibition.

    Directory of Open Access Journals (Sweden)

    Justin Byun

    Full Text Available Slit molecules comprise one of the four canonical families of axon guidance cues that steer the growth cone in the developing nervous system. Apart from their role in axon pathfinding, emerging lines of evidence suggest that a wide range of cellular processes are regulated by Slit, ranging from branch formation and fasciculation during neurite outgrowth to tumor progression and to angiogenesis. However, the molecular and cellular mechanisms downstream of Slit remain largely unknown, in part, because of a lack of a readily manipulatable system that produces easily identifiable traits in response to Slit. The present study demonstrates the feasibility of using the cell line CAD as an assay system to dissect the signaling pathways triggered by Slit. Here, we show that CAD cells express receptors for Slit (Robo1 and Robo2 and that CAD cells respond to nanomolar concentrations of Slit2 by markedly decelerating the rate of process extension. Using this system, we reveal that Slit2 inactivates GSK3β and that inhibition of GSK3β is required for Slit2 to inhibit process outgrowth. Furthermore, we show that Slit2 induces GSK3β phosphorylation and inhibits neurite outgrowth in adult dorsal root ganglion neurons, validating Slit2 signaling in primary neurons. Given that CAD cells can be conveniently manipulated using standard molecular biological methods and that the process extension phenotype regulated by Slit2 can be readily traced and quantified, the use of a cell line CAD will facilitate the identification of downstream effectors and elucidation of signaling cascade triggered by Slit.

  12. Spontaneous Age-Related Neurite Branching in C. elegans

    Science.gov (United States)

    Tank, Elizabeth M. H.; Rodgers, Kasey E.; Kenyon, Cynthia

    2011-01-01

    The analysis of morphological changes that occur in the nervous system during normal aging could provide insight into cognitive decline and neurodegenerative disease. Previous studies have suggested that the nervous system of C. elegans maintains its structural integrity with age despite the deterioration of surrounding tissues. Unexpectedly, we observed that neurons in aging animals frequently displayed ectopic branches, and that the prevalence of these branches increased with time. Within age-matched populations, the branching of mechnosensory neurons correlated with decreased response to light touch and decreased mobility. The incidence of branching was influenced by two pathways that can affect the rate of aging, the Jun kinase pathway and the insulin/IGF-1 pathway. Loss of Jun kinase signaling, which slightly shortens lifespan, dramatically increased and accelerated the frequency of neurite branching. Conversely, inhibition of the daf-2 insulin/IGF-1-like signaling pathway, which extends lifespan, delayed and suppressed branching, and this delay required DAF-16/FOXO activity. Both JNK-1 and DAF-16 appeared to act within neurons in a cell-autonomous manner to influence branching, and, through their tissue-specific expression, it was possible to disconnect the rate at which branching occurred from the overall rate of aging of the animal. Old age has generally been associated with the decline and deterioration of different tissues, except in the case of tumor cell growth. To our knowledge, this is the first indication that aging can potentiate another form of growth, the growth of neurite branches, in normal animals. PMID:21697377

  13. The effect of plant growth regulators, explants and cultivars on ...

    African Journals Online (AJOL)

    To achieve the best explants and media for spinach tissue culture, the effects of two different plant growth regulators, two explants and cultivars on adventitious shoot regeneration were tested. The Analysis of Variance (ANOVA) showed that the effects of plant growth regulators on spinach tissue culture were significant; ...

  14. Endocrine Regulation of Compensatory Growth in Fish

    Directory of Open Access Journals (Sweden)

    Eugene T. Won

    2013-07-01

    Full Text Available Compensatory growth (CG is a period of accelerated growth that occurs following the alleviation of growth-stunting conditions during which an organism can make up for lost growth opportunity and potentially catch-up in size with non-stunted cohorts. Fish show a particularly robust capacity for the response and have been the focus of numerous studies that demonstrate their ability to compensate for periods of fasting once food is made available again. Compensatory growth is characterized by an elevated growth rate resulting from enhanced feed intake, mitogen production and feed conversion efficiency. Because little is known about the underlying mechanisms that drive the response, this review describes the sequential endocrine adaptations that lead to CG; namely during the precedent catabolic phase (fasting that taps endogenous energy reserves, and the following hyperanabolic phase (refeeding when accelerated growth occurs. In order to elicit a CG response, endogenous energy reserves must first be moderately depleted, which alters endocrine profiles that enhance appetite and growth potential. During this catabolic phase, elevated ghrelin and growth hormone (GH production increase appetite and protein-sparing lipolysis, while insulin-like growth factors (IGFs are suppressed, primarily due to hepatic GH resistance. During refeeding, temporal hyperphagia provides an influx of energy and metabolic substrates that are then allocated to somatic growth by resumed IGF signaling. Under the right conditions, refeeding results in hyperanabolism and a steepened growth trajectory relative to constantly fed controls. The response wanes as energy reserves are re-accumulated and homeostasis is restored. We ascribe possible roles for select appetite and growth-regulatory hormones in the context of these catabolic and hyperanabolic phases of the CG response in teleosts, with emphasis on GH, IGFs, cortisol, somatostatin, neuropeptide Y, ghrelin and leptin.

  15. Growth factors regulate glutamine synthetase activity in ...

    African Journals Online (AJOL)

    Khaled

    2012-07-10

    Jul 10, 2012 ... glutamate and ammonia, which in turn, cells are supplied with ammonia ... out to determine the maximum growth time at which cells will be .... Western blot technique for detection the glutamine synthetase enzyme. Lane 1;.

  16. Independent regulation of skeletal growth by Ihh and IGF signaling.

    Science.gov (United States)

    Long, Fanxin; Joeng, Kyu-Sang; Xuan, Shouhong; Efstratiadis, Argiris; McMahon, Andrew P

    2006-10-01

    The insulin-like growth factors (IGFs) play a major role in regulating the systemic growth of mammals. However, it is unclear to what extent their systemic and/or local functions act in concert with other local growth factors controlling the sizes of individual organs. We have specifically addressed whether growth control of the skeleton by IGFs interacts genetically with that by Indian hedgehog (Ihh), a locally produced growth signal for the endochondral skeleton. Here, we report that disruption of both IGF and Ihh signaling resulted in additive reduction in the size of the embryonic skeleton. Thus, IGF and Ihh signaling appear to control the growth of the skeleton in parallel pathways.

  17. Effect of plant growth regulators, explants type and efficient plantlet ...

    African Journals Online (AJOL)

    use

    2011-12-05

    Dec 5, 2011 ... Plant Pathology, Tissue Culture and Biotechnology Laboratory, Department of Botany,. University of ... variability in response to growth regulators. In vitro rooting ..... an adult tree Wrightia tomentosa through enhanced axillary.

  18. Effects of Plant Growth Regulators and Photoperiod on In

    African Journals Online (AJOL)

    Shahin

    using the combination of two plant growth regulators and same photoperiod. Key words: Tissue culture, ... they can be stored and transplanted directly into the field without an acclimatization ..... SAS user's guide. cary, NC: Statistical Analysis ...

  19. Growth regulators, DNA content and anatomy in vitro -cultivated ...

    African Journals Online (AJOL)

    Growth regulators, DNA content and anatomy in vitro -cultivated Curcuma longa ... Shoots were inoculated in MS culture medium with the addition of 30 g/L of sucrose ... flow cytometry, utilizing two reference standards, green pea, and tomato.

  20. Exogenous application of plant growth regulators increased the total ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-02

    Nov 2, 2009 ... the exogenous application of flavonoids reports plant growth regulation ... method used for extraction and quantification of endogenous gibberellins was ... 365 nm) while separation was done on a C18 reverse-phase HPLC.

  1. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

    DEFF Research Database (Denmark)

    Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

    2009-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

  2. Symbiotic regulation of plant growth, development and reproduction

    Science.gov (United States)

    Russell J. Rodriguez; D. Carl Freeman; E. Durant McArthur; Yong Ok Kim; Regina S. Redman

    2009-01-01

    The growth and development of rice (Oryzae sativa) seedlings was shown to be regulated epigenetically by a fungal endophyte. In contrast to un-inoculated (nonsymbiotic) plants, endophyte colonized (symbiotic) plants preferentially allocated resources into root growth until root hairs were well established. During that time symbiotic roots expanded at...

  3. The role of growth regulators, embryo age and genotypes on ...

    African Journals Online (AJOL)

    Administrator

    2011-06-06

    Jun 6, 2011 ... 0.1 mg/l kinetin, MS + 0.1 mg/l IAA and MS + 0.1 mg/l kinetin + 0.1 mg/l IAA were used as growth regulators. ... factor for a high success in zygotic embryo culture is the ... regulators components have proved to influence the.

  4. Business regulation and economic growth in the Western Balkan countries

    Directory of Open Access Journals (Sweden)

    Engjell PERE

    2013-06-01

    Full Text Available Actually economic policies in many countries aimed to stimulate their economic growth, particularly after negative impact of the global economic crisis. In this regards, fiscal regulation are an important aspect of those policies, that can promote or obstacle the economic growth in general. In this point of view this paper aims to analyze the system of administration rules in different Western Balkans Countries, (which includes Albania, Bosnia & Herzegovina, Croatia, Kosovo, Macedonia (FYROM, Montenegro and Serbia. Moreover, a special attention is given investigation of the regulation and administrative facilitation aspects of doing business in the above-mentioned countries, whether this system stimulates, or not, the development of private business and economic growth.The paper is divided into three main sections. The first part provides a retrospective of economic growth in the Western Balkan countries and the dependence of this growth on global economic development. The second part proceeds with the investigations of the impact of administrative regulation on economic growth. The third part, based on an econometric model, will analyze the correlation between economic growth and elaborated indicators which present the level of business administrative regulation system. Furthermore, this last section discusses the results and concludes. In this analysis, the paper is based substantially on the data base of "Doing Business 2013" (World Bank.

  5. Identification of NCAM-binding peptides promoting neurite outgrowth via a heterotrimeric G-protein-coupled pathway

    DEFF Research Database (Denmark)

    Hansen, Raino Kristian; Christensen, Claus; Korshunova, Irina

    2007-01-01

    the fibroblast growth factor receptor, the Src-related non-receptor tyrosine kinase Fyn, and heterotrimeric G-proteins. Interestingly, neurite outgrowth stimulated by ENFIN2 and ENFIN11 was independent of signaling through fibroblast growth factor receptor and Fyn, but could be inhibited with pertussis toxin...

  6. Constitutive Overexpression of the Basic Helix-Loop-Helix Nex1/MATH-2 Transcription Factor Promotes Neuronal Differentiation of PC12 Cells and Neurite Regeneration

    Science.gov (United States)

    Uittenbogaard, Martine; Chiaramello, Anne

    2009-01-01

    Elucidation of the intricate transcriptional pathways leading to neural differentiation and the establishment of neuronal identity is critical to the understanding and design of therapeutic approaches. Among the important players, the basic helix-loop-helix (bHLH) transcription factors have been found to be pivotal regulators of neurogenesis. In this study, we investigate the role of the bHLH differentiation factor Nex1/MATH-2 in conjunction with the nerve growth factor (NGF) signaling pathway using the rat phenochromocytoma PC12 cell line. We report that the expression of Nex1 protein is induced after 5 hr of NGF treatment and reaches maximal levels at 24 hr, when very few PC12 cells have begun extending neurites and ceased cell division. Furthermore, our study demonstrates that Nex1 has the ability to trigger neuronal differentiation of PC12 cells in the absence of neurotrophic factor. We show that Nex1 plays an important role in neurite outgrowth and has the capacity to regenerate neurite outgrowth in the absence of NGF. These results are corroborated by the fact that Nex1 targets a repertoire of distinct types of genes associated with neuronal differentiation, such as GAP-43, βIII-tubulin, and NeuroD. In addition, our findings show that Nex1 up-regulates the expression of the mitotic inhibitor p21WAF1, thus linking neuronal differentiation to cell cycle withdrawal. Finally, our studies show that overexpression of a Nex1 mutant has the ability to block the execution of NGF-induced differentiation program, suggesting that Nex1 may be an important effector of the NGF signaling pathway. PMID:11782967

  7. Toward the Development of an Artificial Brain on a Micropatterned and Material-Regulated Biochip by Guiding and Promoting the Differentiation and Neurite Outgrowth of Neural Stem/Progenitor Cells.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Lei, Kin Fong

    2018-02-14

    An in vitro model mimicking the in vivo environment of the brain must be developed to study neural communication and regeneration and to obtain an understanding of cellular and molecular responses. In this work, a multilayered neural network was successfully constructed on a biochip by guiding and promoting neural stem/progenitor cell differentiation and network formation. The biochip consisted of 3 × 3 arrays of cultured wells connected with channels. Neurospheroids were cultured on polyelectrolyte multilayer (PEM) films in the culture wells. Neurite outgrowth and neural differentiation were guided and promoted by the micropatterns and the PEM films. After 5 days in culture, a 3 × 3 neural network was constructed on the biochip. The function and the connections of the network were evaluated by immunocytochemistry and impedance measurements. Neurons were generated and produced functional and recyclable synaptic vesicles. Moreover, the electrical connections of the neural network were confirmed by measuring the impedance across the neurospheroids. The current work facilitates the development of an artificial brain on a chip for investigations of electrical stimulations and recordings of multilayered neural communication and regeneration.

  8. Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

    Science.gov (United States)

    Lefebvre, P P; Staecker, H; Moonen, G; van de Water, T R

    1993-07-01

    Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations.

  9. Nitroxide radicals formed in situ as polymer chain growth regulators

    International Nuclear Information System (INIS)

    Kolyakina, Elena V; Grishin, Dmitry F

    2009-01-01

    Published data on controlled synthesis of macromolecules using nitroxide radicals, formed in situ during polymerization, as polymer chain growth regulators are systematized and generalized. The attention is focused on the mechanism of polymer chain growth control during reversibly inhibited radical homopolymerization and the effect of structure of precursors and regulating additives on the polymerization kinetics of monomers of different nature and the molecular-mass characteristics of the polymers thus formed. The key methods for generation of nitroxide radicals directly during polymerization are considered. The prospects for development and practical use of these approaches for the synthesis of new polymeric materials are evaluated.

  10. Regulation of dendrite growth and maintenance by exocytosis

    OpenAIRE

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential req...

  11. Effect of growth regulators on growth, flowering and rhizome yield of ...

    African Journals Online (AJOL)

    Field experiments were conducted in 2001 and 2002, to study the effect of foliar application of growth regulators on growth; flowering and rhizome yield of ginger (Zingiber officinale Rosc.). Treatments consisted of gibberellic acid (GA3) at 0,150 and 300 ppm; ethrel at 0,100 and 200 ppm and cycocel (CCC) at 0,250 ppm ...

  12. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  13. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  14. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    International Nuclear Information System (INIS)

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-01-01

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

  15. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  16. The role of growth regulators, embryo age and genotypes on ...

    African Journals Online (AJOL)

    One of the most important problem of tomato breeders is lengthy seed to seed cycle in a breeding program. In vitro techiques provide a lot of advantages for breeders. The objective of this work was to determine the effect of growth regulators and immature embryo age on embryo germination and rapid generation ...

  17. Toxicity of the insect growth regulator lufenuron on the ...

    African Journals Online (AJOL)

    Metarhizium anisopliae has been considered a promising alternative with low environmental impacts for the biological control of a variety of insect-pests. Another alternative is the use of biological pesticides such as insect growth regulators, including lufenuron. An assessment of the potential impact of fungicides on M.

  18. Effect of plant growth regulators on regeneration of the endangered ...

    African Journals Online (AJOL)

    Development of an efficient in vitro regeneration protocol of Calligonum comosum is important and that has achieved to protect the endangered multipurpose medicinally important desert plant in the Kingdom of Bahrain. Nodal segments were used as explants source and the effect of various plant growth regulators (PGRs) ...

  19. Effect of plant growth regulators on callus induction and plant ...

    African Journals Online (AJOL)

    The present study was conducted to investigate the effects of different concentrations and combinations of growth regulators on callus induction and plant regeneration of potato (Solanum tuberosum L.) cultivar Diamant. The tuber segments were used as explants and cultured on Murashige and Skoog (MS) medium ...

  20. The effect of plant growth regulators, explants and cultivars on ...

    African Journals Online (AJOL)

    ONOS

    2010-07-05

    Jul 5, 2010 ... The effect of plant growth regulators, explants and cultivars on spinach (Spinacia oleracea L.) tissue culture. Taha Roodbar Shojaei1*, Vahid Salari2, Darioush Ramazan3, Mahdi Ehyaei1, Javad. Gharechahi4 and Roya Motallebi Chaleshtori5. 1Department of Agronomy and Plant Breeding, College of ...

  1. Callus induction via different growth regulators from cotyledon ...

    African Journals Online (AJOL)

    Cicer arietinum L.) cultivars KK-1 and Hassan-2K on MS and B5 media containing different combinations and concentrations of growth regulators. Different MS and B5 callusing media containing varying level of 2, 4-D (2 and 4 mg/l), NAA (0.50 ...

  2. In vitro production of growth regulators and phosphatase activity by ...

    African Journals Online (AJOL)

    The result showed that the population levels of phosphobacteria were higher in the rhizosphere soil of groundnut plant. Further, all the strains of phosphobacteria were able to produce phytohormones and phosphatase enzyme under in vitro conditions. Keywords: In vitro, phosphobacteria, growth regulators ...

  3. The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Yue Ma

    Full Text Available The inverse F-BAR (IF-BAR domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA-induced neurite initiation and growth in the mouse Neuro2a cells. While ectopic- or over-expression of RhoGAP-defective mutants, srGAP1(R542A and srGAP2(R527A exert a visible inhibitory effect on neuronal differentiation. Unexpectedly, knockdown of endogenous srGAP2 fails to facilitate the neuronal differentiation induced by VPA, but promotes neurite outgrowth of differentiated cells. All three IF-BAR domains from srGAP1-3 can induce filopodia formation in Neuro2a, but the isolated IF-BAR domain from srGAP2, not from srGAP1 and srGAP3, can promote VPA-induced neurite initiation and neuronal differentiation. We identify biochemical and functional interactions of the three srGAPs family members. We propose that srGAP3-Rac1 signaling may be required for the effect of srGAP1 and srGAP2 on attenuating neuronal differentiation. Furthermore, inhibition of Slit-Robo interaction can phenocopy a loss-of-function of srGAP3, indicating that srGAP3 may be dedicated to the Slit-Robo pathway. Our results demonstrate the interplay between srGAP1, srGAP2 and srGAP3 regulates neuronal differentiation and neurite outgrowth. These findings may provide us new insights into the possible roles of srGAPs in neuronal development and a potential mechanism for neurodevelopmental diseases.

  4. Resveratrol Enhances Neurite Outgrowth and Synaptogenesis Via Sonic Hedgehog Signaling Following Oxygen-Glucose Deprivation/Reoxygenation Injury

    Directory of Open Access Journals (Sweden)

    Fanren Tang

    2017-09-01

    Full Text Available Background/Aims: Neurite outgrowth and synaptogenesis are critical steps for functional recovery after stroke. Resveratrol promotes neurite outgrowth and synaptogenesis, but the underlying mechanism is not well understood, although the Sonic hedgehog (Shh signaling pathway may be involved. Given that resveratrol activates sirtuin (Sirt1, the present study examined whether this is mediated by Shh signaling. Methods: Primary cortical neuron cultures were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R. Cell viability and apoptosis were evaluated with Cell Counting Kit 8 and by terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Neurite outgrowth and synaptogenesis were assessed by immunocytochemistry and western blotting, which was also used to examine the expression of Sirt1 and Shh signaling proteins. Results: Resveratrol and the Smoothened (Smo agonist purmophamine, which activates Shh signaling, increased viability, reduced apoptosis, and stimulated neurite outgrowth after OGD/R injury. Moreover, the expression of growth-associated protein(GAP-43, synaptophysin, Shh, Patched (Ptc-1, Smo, glioma-associated oncogene homolog (Gli-1, and Sirt1 were upregulated under these conditions. These effects were reversed by treatment with the Smo inhibitor cyclopamine, whereas the Sirt1 inhibitor sirtinol reduced the levels of Shh, Ptc-1, Smo, and Gli-1. Conclusions: Resveratrol reduces neuronal injury following OGD/R injury and enhances neurite outgrowth and synaptogenesis by activating Shh signaling, which in turn induces Sirt1.

  5. Induction of neurite outgrowth in 3D hydrogel-based environments

    International Nuclear Information System (INIS)

    Assunção-Silva, Rita C; Oliveira, Cátia Costa; Gomes, Eduardo D; Sousa, Nuno; Silva, Nuno A; Salgado, António J; Ziv-Polat, Ofra; Sahar, Abraham

    2015-01-01

    The ability of peripheral nervous system (PNS) axons to regenerate and re-innervate their targets after an injury has been widely recognized. However, despite the considerable advances made in microsurgical techniques, complete functional recovery is rarely achieved, especially for severe peripheral nerve injuries (PNIs). Therefore, alternative therapies that can successfully repair peripheral nerves are still essential. In recent years the use of biodegradable hydrogels enriched with growth-supporting and guidance cues, cell transplantation, and biomolecular therapies have been explored for the treatment of PNIs. Bearing this in mind, the aim of this study was to assess whether Gly-Arg-Gly-Asp-Ser synthetic peptide (GRGDS)-modified gellan gum (GG) based hydrogels could foster an amenable environment for neurite/axonal growth. Additionally, strategies to further improve the rate of neurite outgrowth were also tested, namely the use of adipose tissue derived stem cells (ASCs), as well as the glial derived neurotrophic factor (GDNF). In order to increase its stability and enhance its bioactivity, the GDNF was conjugated covalently to iron oxide nanoparticles (IONPs). The impact of hydrogel modification as well as the effect of the GDNF-IONPs on ASC behavior was also screened. The results revealed that the GRGDS-GG hydrogel was able to support dorsal root ganglia (DRG)-based neurite outgrowth, which was not observed for non-modified hydrogels. Moreover, the modified hydrogels were also able to support ASCs attachment. In contrast, the presence of the GDNF-IONPs had no positive or negative impact on ASC behavior. Further experiments revealed that the presence of ASCs in the hydrogel improved axonal growth. On the other hand, GDNF-IONPs alone or combined with ASCs significantly increased neurite outgrowth from DRGs, suggesting a beneficial role of the proposed strategy for future applications in PNI regenerative medicine. (note)

  6. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  7. Regulation of intestinal mucosal growth by amino acids.

    Science.gov (United States)

    Ray, Ramesh M; Johnson, Leonard R

    2014-03-01

    Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as epidermal growth factor and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis, or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1, and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine, and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the

  8. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

    Science.gov (United States)

    Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

    2011-01-01

    Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

  9. Critical time window of neuronal cholesterol synthesis during neurite outgrowth.

    Science.gov (United States)

    Fünfschilling, Ursula; Jockusch, Wolf J; Sivakumar, Nandhini; Möbius, Wiebke; Corthals, Kristina; Li, Sai; Quintes, Susanne; Kim, Younghoon; Schaap, Iwan A T; Rhee, Jeong-Seop; Nave, Klaus-Armin; Saher, Gesine

    2012-05-30

    Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have conditionally ablated the cholesterol biosynthesis in these neurons in mice either embryonically or postnatally. We found that cortical projection neurons synthesize cholesterol during their entire lifetime. At all stages, they can also benefit from glial support. Adult neurons that lack cholesterol biosynthesis are mainly supported by astrocytes such that their functional integrity is preserved. In contrast, microglial cells support young neurons. However, compensatory efforts of microglia are only transient leading to layer-specific neuronal death and the reduction of cortical projections. Hence, during the phase of maximal membrane growth and maximal cholesterol demand, neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons revealed that neurons tolerate only slight alteration in the cholesterol content and plasma membrane tension. This quality control allows neurons to differentiate normally and adjusts the extent of neurite outgrowth, the number of functional growth cones and synapses to the available cholesterol. This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases.

  10. New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Chien-Hung Shih

    Full Text Available Neurite outgrowth is an essential process for the establishment of the nervous system. Brain-derived neurotrophic factor (BDNF binds to its receptor TrkB and regulates axonal and dendritic morphology of neurons through signal transduction and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular signaling in various physiological processes. The purpose of this study is to investigate the role of SH2B1 in the development of the central nervous system. In this study, we show that knocking down SH2B1 reduces neurite formation of cortical neurons whereas overexpression of SH2B1β promotes the development of hippocampal neurons. We further demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth and signaling using the established PC12 cells stably expressing TrkB, SH2B1β or SH2B1β mutants. Our data indicate that overexpressing SH2B1β enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest that these two pathways are required for SH2B1β-promoted BDNF-induced neurite outgrowth. Moreover, SH2B1β enhances BDNF-stimulated phosphorylation of signal transducer and activator of transcription 3 at serine 727. Finally, our data indicate that the SH2 domain and tyrosine phosphorylation of SH2B1β contribute to BDNF-induced signaling pathways and neurite outgrowth. Taken together, these findings demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth through enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.

  11. Auxin-BR Interaction Regulates Plant Growth and Development

    Science.gov (United States)

    Tian, Huiyu; Lv, Bingsheng; Ding, Tingting; Bai, Mingyi; Ding, Zhaojun

    2018-01-01

    Plants develop a high flexibility to alter growth, development, and metabolism to adapt to the ever-changing environments. Multiple signaling pathways are involved in these processes and the molecular pathways to transduce various developmental signals are not linear but are interconnected by a complex network and even feedback mutually to achieve the final outcome. This review will focus on two important plant hormones, auxin and brassinosteroid (BR), based on the most recent progresses about these two hormone regulated plant growth and development in Arabidopsis, and highlight the cross-talks between these two phytohormones. PMID:29403511

  12. Ihh signaling regulates mandibular symphysis development and growth.

    Science.gov (United States)

    Sugito, H; Shibukawa, Y; Kinumatsu, T; Yasuda, T; Nagayama, M; Yamada, S; Minugh-Purvis, N; Pacifici, M; Koyama, E

    2011-05-01

    Symphyseal secondary cartilage is important for mandibular development, but the molecular mechanisms underlying its formation remain largely unknown. Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and growth. By embryonic days 16.5 to 18.5, Sox9-expressing chondrocytes formed within condensed Tgfβ-1/Runx2-expressing mesenchymal cells at the prospective symphyseal joint site, and established a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns. In post-natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differentiated into chondrocytes, and contributed to anterior growth of alveolar bone. In Ihh-null mice, however, symphyseal development was defective, mainly because of enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells. Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal development. Thus, Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth.

  13. Productivity growth and price regulation of Slovenian water distribution utilities

    Directory of Open Access Journals (Sweden)

    Jelena Zorić

    2010-06-01

    Full Text Available This paper aims to analyse the price regulation method and performance of thewater industry in Slovenia. A stochastic cost frontier model is employed to estimate and decompose the total factor productivity (TFP growth of water distribution utilities in the 1997-2003 period. The main goal is to find out whether the lack of proper incentives to improve performance has resulted in the low TFP growth of Slovenian water distribution utilities. The evidence suggests that cost inefficiencies are present in water utilities, which indicates considerable cost saving potential in the analysed industry. Technical change is found to have positively affected the TFP growth over time, while cost inefficiency levels remained essentially unchanged. Overall, the average annual TFP growth in the analysed period is estimated to be only slightly above zero, which is a relatively poor result. This can largely be contributed to the present institutional and regulatory setting that does not stimulate utilities to improve productivity. Therefore, the introduction of an independent regulatory agency and an incentive-based price regulation scheme should be seriously considered in order to enhance the performance of Slovenian water distribution utilities.

  14. Regulation of dendrite growth and maintenance by exocytosis

    Science.gov (United States)

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382

  15. Growth of maize coleoptiles in the presence of natural and synthetic growth regulators. Growth correlations

    Directory of Open Access Journals (Sweden)

    Ewa Raczek

    2014-01-01

    Full Text Available The effect of natural (IAA, FC, ABA and synthetic (2,4-D growth substances on the increase of the fresh weight of maize coleoptile segments and change of the pH of the incubation medium, accepted here as criteria of maize coleoptile growth, was studied. The growth of maize coleoptiles depended on the concentration of the growth substances, as well as, on the composition of the incubation medium. The highest stimulation of coleoptile growth was seen with FC at a concentration of 10-4M, whereas ABA at 10-3 M gave the highest inhibition of maize coleoptile fresh weight increase and caused alkalization of the medium. The presence of K+ ions in the incubation medium enhanced the stimulatory effect of IAA and FC on the increase of the coleoptile fresh weight, whereas the presence of these ions and phosphate buffer abolished the growth-promoting effect of IAA and FC. The best correlation of the "fresh weight" and "pH" effects was found in the case of the growth of maize coleoptiles in the presence of FC (rxy = 0.67. The inhibition of maize coleoptile growth in the presence of high concentrations of IAA can be explained by the destructive effect of natural auxin at these concentrations on the integrity of mitochondrial membranes, and therefore on the normal functioning of mitochondria.

  16. Electrical Stimulation of Schwann Cells Promotes Sustained Increases in Neurite Outgrowth

    OpenAIRE

    Koppes, Abigail N.; Nordberg, Andrea L.; Paolillo, Gina M.; Goodsell, Nicole M.; Darwish, Haley A.; Zhang, Linxia; Thompson, Deanna M.

    2013-01-01

    Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite ou...

  17. MHC class II molecules regulate growth in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K

    1994-01-01

    MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

  18. Effects of different plant growth regulators on blueberry fruit quality

    Science.gov (United States)

    Zhang, X. C.; Zhu, Y. Q.; Wang, Y. N.; Luo, C.; Wang, X.

    2017-08-01

    In order to understand the effects of different plant growth regulators (PGRs) on blueberry fruit growth, various concentrations of Abscisic acid (ABA), Methyl jasmonate (MJ), Brassinolide (BR), Melatonin (MT) were sprayed on blueberry cv. ‘Brigita’ fruits. The results showed that all the PGRs put into effect on improving the quality of blueberry fruit. Comparing with the control plants no PGR spraying,300 mg/L of MT treatment promoted effectively accumulation of the soluble sugar. ABA 20mg/L treatment in-creased effectively accumulation of anthocyanin, and significantly decreased titratable acid content. The treatment of MJ 10mg/L improved significantly the soluble solid content. The effect of the four PGRs treatments on appearance did not show obvious difference.

  19. Role of Estrogen in Thyroid Function and Growth Regulation

    Directory of Open Access Journals (Sweden)

    Ana Paula Santin

    2011-01-01

    Full Text Available Thyroid diseases are more prevalent in women, particularly between puberty and menopause. It is wellknown that estrogen (E has indirect effects on the thyroid economy. Direct effects of this steroid hormone on thyroid cells have been described more recently; so, the aim of the present paper was to review the evidences of these effects on thyroid function and growth regulation, and its mechanisms. The expression and ratios of the two E receptors, α and β, that mediate the genomic effects of E on normal and abnormal thyroid tissue were also reviewed, as well as nongenomic, distinct molecular pathways. Several evidences support the hypothesis that E has a direct role in thyroid follicular cells; understanding its influence on the growth and function of the thyroid in normal and abnormal conditions can potentially provide new targets for the treatment of thyroid diseases.

  20. Fluoxetine regulates cell growth inhibition of interferon-α.

    Science.gov (United States)

    Lin, Yu-Min; Yu, Bu-Chin; Chiu, Wen-Tai; Sun, Hung-Yu; Chien, Yu-Chieh; Su, Hui-Chen; Yen, Shu-Yang; Lai, Hsin-Wen; Bai, Chyi-Huey; Young, Kung-Chia; Tsao, Chiung-Wen

    2016-10-01

    Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

  1. Metabolic regulation of mycobacterial growth and antibiotic sensitivity.

    Directory of Open Access Journals (Sweden)

    Seung-Hun Baek

    2011-05-01

    Full Text Available Treatment of chronic bacterial infections, such as tuberculosis (TB, requires a remarkably long course of therapy, despite the availability of drugs that are rapidly bacteriocidal in vitro. This observation has long been attributed to the presence of bacterial populations in the host that are "drug-tolerant" because of their slow replication and low rate of metabolism. However, both the physiologic state of these hypothetical drug-tolerant populations and the bacterial pathways that regulate growth and metabolism in vivo remain obscure. Here we demonstrate that diverse growth-limiting stresses trigger a common signal transduction pathway in Mycobacterium tuberculosis that leads to the induction of triglyceride synthesis. This pathway plays a causal role in reducing growth and antibiotic efficacy by redirecting cellular carbon fluxes away from the tricarboxylic acid cycle. Mutants in which this metabolic switch is disrupted are unable to arrest their growth in response to stress and remain sensitive to antibiotics during infection. Thus, this regulatory pathway contributes to antibiotic tolerance in vivo, and its modulation may represent a novel strategy for accelerating TB treatment.

  2. 7, 8, 3′-Trihydroxyflavone Promotes Neurite Outgrowth and Protects Against Bupivacaine-Induced Neurotoxicity in Mouse Dorsal Root Ganglion Neurons

    Science.gov (United States)

    Shi, Haohong; Luo, Xingjing

    2016-01-01

    Background 7, 8, 3′-trihydroxyflavone (THF) is a novel pro-neuronal small molecule that acts as a TrkB agonist. In this study, we examined the effect of THF on promoting neuronal growth and protecting anesthetics-induced neurotoxicity in dorsal root ganglion (DRG) neurons in vitro. Material/Methods Neonatal mouse DRG neurons were cultured in vitro and treated with various concentrations of THF. The effect of THF on neuronal growth was investigated by neurite outgrowth assay and Western blot. In addition, the protective effects of THF on bupivacaine-induced neurotoxicity were investigated by apoptosis TUNEL assay, neurite outgrowth assay, and Western blot, respectively. Results THF promoted neurite outgrowth of DRG neurons in dose-dependent manner, with an EC50 concentration of 67.4 nM. Western blot analysis showed THF activated TrkB signaling pathway by inducing TrkB phosphorylation. THF also rescued bupivacaine-induced neurotoxicity by reducing apoptosis and protecting neurite retraction in DRG neurons. Furthermore, the protection of THF in bupivacaine-injured neurotoxicity was directly associated with TrkB phosphorylation in a concentration-dependent manner in DRG neurons. Conclusions THF has pro-neuronal effect on DRG neurons by promoting neurite growth and protecting against bupivacaine-induced neurotoxicity, likely through TrkB activation. PMID:27371503

  3. Neurite, a finite difference large scale parallel program for the simulation of electrical signal propagation in neurites under mechanical loading.

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    Julián A García-Grajales

    Full Text Available With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite--explicit and implicit--were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon

  4. Economic growth and energy regulation in the environmental Kuznets curve.

    Science.gov (United States)

    Lorente, Daniel Balsalobre; Álvarez-Herranz, Agustín

    2016-08-01

    This study establishes the existence of a pattern of behavior, between economic growth and environmental degradation, consistent with the environmental Kuznets curve (EKC) hypothesis for 17 Organization for Economic Cooperation and Development (OECD) countries between 1990 and 2012. Based on this EKC pattern, it shows that energy regulation measures help reduce per capita greenhouse gas (GHG) emissions. To validate this hypothesis, we also add the explanatory variables: renewable energy promotion, energy innovation processes, and the suppression effect of income level on the contribution of renewable energy sources to total energy consumption. It aims to be a tool for decision-making regarding energy policy. This paper provides a two-stage econometric analysis of instrumental variables with the aim of correcting the existence of endogeneity in the variable GDP per capita, verifying that the instrumental variables used in this research are appropriate for our aim. To this end, it first makes a methodological contribution before incorporating additional variables associated with environmental air pollution into the EKC hypothesis and showing how they positively affect the explanation of the correction in the GHG emission levels. This study concludes that air pollution will not disappear on its own as economic growth increases. Therefore, it is necessary to promote energy regulation measures to reduce environmental pollution.

  5. Growth regulators and substrates for Oncidium baueri Lindl. micropropagation

    Directory of Open Access Journals (Sweden)

    Daniele Brandstetter Rodrigues

    2016-10-01

    Full Text Available An adequate concentration of growth regulators as well as the replacement of agar by an alternative medium may be promising from practical and financial points of view to produce orchid plants by micropropagation. The objective of this work was to evaluate different concentrations of growth regulator and alternative substrates for agar replacement in culture medium for in vitro multiplication and rooting of Oncidium baueri. In the explant multiplication phase, two experimental factors were evaluated- various concentrations of 6-benzylaminopurine (BAP (0.0, 1.0, 2.0, and 3.0 mg L-1 and substrates (agar, vermiculite, and coconut fiber added to MS medium. In the rooting phase, different concentrations of indole butyric acid (IBA (0.0, 0.5, 1.0, and 1.5 mg L-1 were added to culture medium containing the same substrate. Six months after the experiments were initiated, the survival percentage, number of leaves, shoots, and roots and length of the aerial part and the major root were evaluated. The results suggested that addition of 1.0 mg L-1 BAP is necessary for the O. baueri in vitro multiplication phase, but IBA is not necessary in the rooting phase. For the substrate, vermiculite is not indicated as an agar replacement. In contrast, coconut fiber can be used in both multiplication and rooting phases of Oncidium baueri in vitro culture.

  6. Neurofibromin regulates somatic growth through the hypothalamic–pituitary axis

    Science.gov (United States)

    Hegedus, Balazs; Yeh, Tu-Hsueh; Lee, Da Yong; Emnett, Ryan J.; Li, Jia; Gutmann, David H.

    2008-01-01

    To study the role of the neurofibromatosis-1 (NF1) gene in mammalian brain development, we recently generated mice in which Nf1 gene inactivation occurs in neuroglial progenitor cells using the brain lipid binding protein (BLBP) promoter. We found that Nf1BLBPCKO mice exhibit significantly reduced body weights and anterior pituitary gland sizes. We further demonstrate that the small anterior pituitary size reflects loss of neurofibromin expression in the hypothalamus, leading to reduced growth hormone releasing hormone, pituitary growth hormone (GH) and liver insulin-like growth factor-1 (IGF1) production. Since neurofibromin both negatively regulates Ras activity and positively modulates cAMP levels, we examined the signaling pathway responsible for these abnormalities. While BLBP-mediated expression of an activated Ras molecule did not recapitulate the body weight and hypothalamic/pituitary defects, treatment of Nf1BLBPCKO mice with rolipram to increase cAMP levels resulted in a partial restoration of the body weight phenotype. Furthermore, conditional expression of the Ras regulatory GAP domain of neurofibromin also did not rescue the body weight or Igf1 mRNA defects in Nf1BLBPCKO mice. Collectively, these data demonstrate a critical role for neurofibromin in hypothalamic–pituitary axis function and provide further insights into the short stature and GH deficits seen in children with NF1. PMID:18614544

  7. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

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    Santiago Vernia

    2016-03-01

    Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

  8. TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling.

    Science.gov (United States)

    Heiser, Jeanine H; Schuwald, Anita M; Sillani, Giacomo; Ye, Lian; Müller, Walter E; Leuner, Kristina

    2013-11-01

    The non-selective cationic transient receptor canonical 6 (TRPC6) channels are involved in synaptic plasticity changes ranging from dendritic growth, spine morphology changes and increase in excitatory synapses. We previously showed that the TRPC6 activator hyperforin, the active antidepressant component of St. John's wort, induces neuritic outgrowth and spine morphology changes in PC12 cells and hippocampal CA1 neurons. However, the signaling cascade that transmits the hyperforin-induced transient rise in intracellular calcium into neuritic outgrowth is not yet fully understood. Several signaling pathways are involved in calcium transient-mediated changes in synaptic plasticity, ranging from calmodulin-mediated Ras-induced signaling cascades comprising the mitogen-activated protein kinase, PI3K signal transduction pathways as well as Ca(2+) /calmodulin-dependent protein kinase II (CAMKII) and CAMKIV. We show that several mechanisms are involved in TRPC6-mediated synaptic plasticity changes in PC12 cells and primary hippocampal neurons. Influx of calcium via TRPC6 channels activates different pathways including Ras/mitogen-activated protein kinase/extracellular signal-regulated kinases, phosphatidylinositide 3-kinase/protein kinase B, and CAMKIV in both cell types, leading to cAMP-response element binding protein phosphorylation. These findings are interesting not only in terms of the downstream targets of TRPC6 channels but also because of their potential to facilitate further understanding of St. John's wort extract-mediated antidepressant activity. Alterations in synaptic plasticity are considered to play an important role in the pathogenesis of depression. Beside several other proteins, TRPC6 channels regulate synaptic plasticity. This study demonstrates that different pathways including Ras/MEK/ERK, PI3K/Akt, and CAMKIV are involved in the improvement of synaptic plasticity by the TRPC6 activator hyperforin, the antidepressant active constituent of St. John

  9. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  10. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-01-01

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  11. Sulfur availability regulates plant growth via glucose-TOR signaling.

    Science.gov (United States)

    Dong, Yihan; Silbermann, Marleen; Speiser, Anna; Forieri, Ilaria; Linster, Eric; Poschet, Gernot; Allboje Samami, Arman; Wanatabe, Mutsumi; Sticht, Carsten; Teleman, Aurelio A; Deragon, Jean-Marc; Saito, Kazuki; Hell, Rüdiger; Wirtz, Markus

    2017-10-27

    Growth of eukaryotic cells is regulated by the target of rapamycin (TOR). The strongest activator of TOR in metazoa is amino acid availability. The established transducers of amino acid sensing to TOR in metazoa are absent in plants. Hence, a fundamental question is how amino acid sensing is achieved in photo-autotrophic organisms. Here we demonstrate that the plant Arabidopsis does not sense the sulfur-containing amino acid cysteine itself, but its biosynthetic precursors. We identify the kinase GCN2 as a sensor of the carbon/nitrogen precursor availability, whereas limitation of the sulfur precursor is transduced to TOR by downregulation of glucose metabolism. The downregulated TOR activity caused decreased translation, lowered meristematic activity, and elevated autophagy. Our results uncover a plant-specific adaptation of TOR function. In concert with GCN2, TOR allows photo-autotrophic eukaryotes to coordinate the fluxes of carbon, nitrogen, and sulfur for efficient cysteine biosynthesis under varying external nutrient supply.

  12. Chondroitin-4-sulfation negatively regulates axonal guidance and growth

    Science.gov (United States)

    Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

    2008-01-01

    Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

  13. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  14. Pleurotus giganteus (Berk.) Karunarathna & K.D. Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells.

    Science.gov (United States)

    Phan, Chia-Wei; Wong, Wei-Lun; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

    2012-07-19

    Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal. The fruiting bodies P. giganteus were analysed for its nutritional values. Cytotoxicity of the mushroom's aqueous and ethanolic extracts towards PC12, a rat pheochromocytoma cell line was assessed by using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Neurite outgrowth stimulation assay was carried out with nerve growth factor (NGF) as control. To elucidate signaling mechanisms involved by mushroom extract-induced neurite outgrowth, treatment of specific inhibitor for MEK/ERK and PI3K signalling pathway was carried out. The fruiting bodies of P. giganteus were found to have high carbohydrate, dietary fibre, potassium, phenolic compounds and triterpenoids. Both aqueous and ethanolic extracts induced neurite outgrowth of PC12 cells in a dose- and time-dependant manner with no detectable cytotoxic effect. At day 3, 25 μg/ml of aqueous extract and 15 μg/ml of ethanolic extract showed the highest percentage of neurite-bearing cells, i.e. 31.7 ± 1.1% and 33.3 ± 0.9%; respectively. Inhibition treatment results suggested that MEK/ERK and PI3K/Akt are responsible for neurite outgrowth of PC12 cells stimulated by P. giganteus extract. The high potassium content (1345.7 mg/100 g) may be responsible for promoting neurite extension, too. P. giganteus contains bioactive compounds that mimic NGF and are responsible for neurite stimulation. Hence, this mushroom may be

  15. Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol.

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    Kenji Hashimoto

    Full Text Available Cilostazol, a type-3 phosphodiesterase (PDE3 inhibitor, has become widely used as an antiplatelet drug worldwide. A recent second Cilostazol Stroke Prevention Study demonstrated that cilostazol is superior to aspirin for prevention of stroke after an ischemic stroke. However, its precise mechanisms of action remain to be determined. Here, we report that cilostazol, but not the PDE3 inhibitors cilostamide and milrinone, significantly potentiated nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Furthermore, specific inhibitors for the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP(3 receptors and several common signaling pathways (PLC-γ, PI3K, Akt, p38 MAPK, and c-Jun N-terminal kinase (JNK, and the Ras/Raf/ERK/MAPK significantly blocked the potentiation of NGF-induced neurite outgrowth by cilostazol. Using a proteomics analysis, we identified that levels of eukaryotic translation elongation factor eEF1A1 protein were significantly increased by treatment with cilostazol, but not cilostamide, in PC12 cells. Moreover, the potentiating effects of cilostazol on NGF-induced neurite outgrowth were significantly antagonized by treatment with eEF1A1 RNAi, but not the negative control of eEF1A1. These findings suggest that eEF1A1 and several common cellular signaling pathways might play a role in the mechanism of cilostazol-induced neurite outgrowth. Therefore, agents that can increase the eEF1A1 protein may have therapeutic relevance in diverse conditions with altered neurite outgrowth.

  16. Differential responses of onion and garlic against plant growth regulators

    International Nuclear Information System (INIS)

    Oozunidou, G.; Asif, M.; Giannakuola, A.; Iliass, A.

    2011-01-01

    The effects of Gibberellic acid-GA3, Prohexadione-Calcium, and Ethephon pre-harvest application on yield, biomass production, photosynthetic function, lipid peroxidation and quality characteristics of onion (Allium cepa L.) and garlic (Allium sativum L.) plants were investigated. Shoot length and biomass of onion and garlic, expressed either in fresh or dry weight, increased significantly under GA3, while a progressive decrease under Prohex-Ca and Ethephon occurred. Higher MDA (lipid peroxidation) values were recorded after Prohex-Ca and Ethephon supply on onion and garlic plants; it seems that GA3 treatment prevents lipid peroxidation as measured with the help of the TBARS method. Plants treated with Prohex-Ca and Ethephon revealed higher peroxidase activity compared to control and GA3 treated plants. Considering the results of MDA content and peroxidase activities it can be assumed that GA3 treated plants are slightly protected from the natural course of oxidative stress, which occurs during ageing as observed for control samples. The fluctuations of chlorophyll fluorescence parameters represent a general decline in chloroplasts function after plant growth regulators exposure, whereas in combination to the suppressed chlorophyll content, structural malformations of photo systems may also occur. The production of ascorbic acid, glucose and fructose content seems to be enhanced under GA3 in both species, while their values were depressed under Prohex-Ca and Ethephon. Overall, only GA3 supply leads to a vigorous onion and garlic growth and yield. (author)

  17. Symbiotic regulation of plant growth, development and reproduction

    Science.gov (United States)

    Rodriguez, R.J.; Freeman, D. Carl; McArthur, E.D.; Kim, Y.-O.; Redman, R.S.

    2009-01-01

    The growth and development of rice (Oryzae sativa) seedlings was shown to be regulated epigenetically by a fungal endophyte. In contrast to un-inoculated (nonsymbiotic) plants, endophyte colonized (symbiotic) plants preferentially allocated resources into root growth until root hairs were well established. During that time symbiotic roots expanded at five times the rate observed in nonsymbiotic plants. Endophytes also influenced sexual reproduction of mature big sagebrush (Artemisia tridentata) plants. Two spatially distinct big sagebrush subspecies and their hybrids were symbiotic with unique fungal endophytes, despite being separated by only 380 m distance and 60 m elevation. A double reciprocal transplant experiment of parental and hybrid plants, and soils across the hybrid zone showed that fungal endophytes interact with the soils and different plant genotypes to confer enhanced plant reproduction in soil native to the endophyte and reduced reproduction in soil alien to the endophyte. Moreover, the most prevalent endophyte of the hybrid zone reduced the fitness of both parental subspecies. Because these endophytes are passed to the next generation of plants on seed coats, this interaction provides a selective advantage, habitat specificity, and the means of restricting gene flow, thereby making the hybrid zone stable, narrow and potentially leading to speciation. ?? 2009 Landes Bioscience.

  18. Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

    Directory of Open Access Journals (Sweden)

    Breuninger Holger

    2012-03-01

    Full Text Available Abstract Background Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB, a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation. Results To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved. Conclusions This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.

  19. Expressionof Drosophila FOXO regulates growth and can phenocopy starvation

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    Lockyer Joseph M

    2003-07-01

    Full Text Available Abstract Background Components of theinsulin signaling pathway are important regulators of growth. TheFOXO (forkhead box, sub-group "O" transcriptionfactors regulate cellular processes under conditions of low levelsof insulin signaling. Studies in mammalian cell culture show thatactivation of FOXO transcription factors causes cell death or cellcycle arrest. The Caenorhabiditis elegans homologue ofFOXO, Daf-16, is required for the formation of dauer larvae in responseto nutritional stress. In addition, FOXO factors have been implicatedin stress resistance and longevity. Results We have identifiedthe Drosophila melanogaster homologue of FOXO (dFOXO,which is conserved in amino acid sequence compared with the mammalianFOXO homologues and Daf-16. Expression of dFOXO during early larvaldevelopment causes inhibition of larval growth and alterations infeeding behavior. Inhibition of larval growth is reversible upondiscontinuation of dFOXO expression. Expression of dFOXO duringthe third larval instar or at low levels during development leadsto the generation of adults that are reduced in size. Analysis ofthe wings and eyes of these small flies indicates that the reductionin size is due to decreases in cell size and cell number. Overexpressionof dFOXO in the developing eye leads to a characteristic phenotypewith reductions in cell size and cell number. This phenotype canbe rescued by co-expression of upstream insulin signaling components,dPI3K and dAkt, however, this rescue is not seen when FOXO is mutatedto a constitutively active form. Conclusions dFOXO is conservedin both sequence and regulatory mechanisms when compared with otherFOXO homologues. The establishment of Drosophila as a model forthe study of FOXO transcription factors should prove beneficialto determining the biological role of these signaling molecules.The alterations in larval development seen upon overexpression ofdFOXO closely mimic the phenotypic effects of starvation, suggestinga

  20. β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells.

    Science.gov (United States)

    Salto, Rafael; Vílchez, Jose D; Girón, María D; Cabrera, Elena; Campos, Nefertiti; Manzano, Manuel; Rueda, Ricardo; López-Pedrosa, Jose M

    2015-01-01

    β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.

  1. Glial membranes at the node of Ranvier prevent neurite outgrowth

    DEFF Research Database (Denmark)

    Huang, Jeffrey K; Phillips, Greg R; Roth, Alejandro D

    2005-01-01

    of neurite outgrowth, including the oligodendrocyte myelin glycoprotein (OMgp). In rat spinal cord, OMgp was not localized to compact myelin, as previously thought, but to oligodendroglia-like cells, whose processes converge to form a ring that completely encircles the nodes. In OMgp-null mice, CNS nodes......Nodes of Ranvier are regularly placed, nonmyelinated axon segments along myelinated nerves. Here we show that nodal membranes isolated from the central nervous system (CNS) of mammals restricted neurite outgrowth of cultured neurons. Proteomic analysis of these membranes revealed several inhibitors...

  2. Ligand Receptor-Mediated Regulation of Growth in Plants.

    Science.gov (United States)

    Haruta, Miyoshi; Sussman, Michael R

    2017-01-01

    Growth and development of multicellular organisms are coordinately regulated by various signaling pathways involving the communication of inter- and intracellular components. To form the appropriate body patterns, cellular growth and development are modulated by either stimulating or inhibiting these pathways. Hormones and second messengers help to mediate the initiation and/or interaction of the various signaling pathways in all complex multicellular eukaryotes. In plants, hormones include small organic molecules, as well as larger peptides and small proteins, which, as in animals, act as ligands and interact with receptor proteins to trigger rapid biochemical changes and induce the intracellular transcriptional and long-term physiological responses. During the past two decades, the availability of genetic and genomic resources in the model plant species, Arabidopsis thaliana, has greatly helped in the discovery of plant hormone receptors and the components of signal transduction pathways and mechanisms used by these immobile but highly complex organisms. Recently, it has been shown that two of the most important plant hormones, auxin and abscisic acid (ABA), act through signaling pathways that have not yet been recognized in animals. For example, auxins stimulate cell elongation by bringing negatively acting transcriptional repressor proteins to the proteasome to be degraded, thus unleashing the gene expression program required for increasing cell size. The "dormancy" inducing hormone, ABA, binds to soluble receptor proteins and inhibits a specific class of protein phosphatases (PP2C), which activates phosphorylation signaling leading to transcriptional changes needed for the desiccation of the seeds prior to entering dormancy. While these two hormone receptors have no known animal counterparts, there are also many similarities between animal and plant signaling pathways. For example, in plants, the largest single gene family in the genome is the protein kinase

  3. Matrix rigidity regulates cancer cell growth and cellular phenotype.

    Directory of Open Access Journals (Sweden)

    Robert W Tilghman

    2010-09-01

    Full Text Available The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness of the microenvironment and how this response varies among cancer cell lines.In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: "rigidity dependent" (those which show an increase in cell growth as extracellular rigidity is increased, and "rigidity independent" (those which grow equally on both soft and stiff substrates. Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug.These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models.

  4. Matrix Rigidity Regulates Cancer Cell Growth and Cellular Phenotype

    Science.gov (United States)

    Tilghman, Robert W.; Cowan, Catharine R.; Mih, Justin D.; Koryakina, Yulia; Gioeli, Daniel; Slack-Davis, Jill K.; Blackman, Brett R.; Tschumperlin, Daniel J.; Parsons, J. Thomas

    2010-01-01

    Background The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness) of the microenvironment and how this response varies among cancer cell lines. Methodology/Principal Findings In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: “rigidity dependent” (those which show an increase in cell growth as extracellular rigidity is increased), and “rigidity independent” (those which grow equally on both soft and stiff substrates). Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug. Conclusions/Significance These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models. PMID:20886123

  5. Effect of plant growth regulators on production of alpha-linolenic ...

    Indian Academy of Sciences (India)

    Sujana Kokkiligadda

    2017-10-05

    Oct 5, 2017 ... MS received 13 October 2016; revised 22 March 2017; accepted 30 May 2017; ... Plant growth regulators; microalgae; Chlorella pyrenoidosa; alpha-linolenic acid. 1. ... the growth period by flocculation method [9] using alum.

  6. Discovery of pyrroloimidazoles as agents stimulating neurite outgrowth

    NARCIS (Netherlands)

    Beck, Barbara; Leppert, Christian A.; Mueller, Bernhard K.; Dömling, Alexander

    2006-01-01

    A diverse library of substituted pyrroloimidazoles was assembled by a multicomponent reaction (MCR) of tosylmethyl isocyanides (TOSMIC), indole carbaldehydes and primary amines in a van Leusen reaction. A library of this scaffold was screened in a phenotypic assay for neurite outgrowth. Several

  7. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

    Directory of Open Access Journals (Sweden)

    Jui-Heng Tseng

    2017-08-01

    Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

  8. Electrospun fiber surface nanotopography influences astrocyte-mediated neurite outgrowth.

    Science.gov (United States)

    Johnson, Christopher D; D'Amato, Anthony R; Puhl, Devan L; Wich, Douglas M; Vespermann, Amanda; Gilbert, Ryan J

    2018-05-15

    Aligned, electrospun fiber scaffolds provide topographical guidance for regenerating neurons and glia after central nervous system injury. To date, no study has explored how fiber surface nanotopography affects astrocyte response to fibrous scaffolds. Astrocytes play important roles in the glial scar, the blood brain barrier, and in maintaining homeostasis in the central nervous system. In this study, electrospun poly L-lactic acid fibers were engineered with smooth, pitted, or divoted surface nanotopography. Cortical or spinal cord primary rat astrocytes were cultured on the surfaces for either 1 or 3 days to examine the astrocyte response over time. The results showed that cortical astrocytes were significantly shorter and broader on the pitted and divoted fibers compared to those on smooth fibers. However, spinal cord astrocyte morphology was not significantly altered by the surface features. These findings indicate that astrocytes from unique anatomical locations respond differently to the presence of nanotopography. Western Blot results show that the differences in morphology were not associated with significant changes in GFAP or vinculin in either astrocyte population, suggesting that surface pits and divots do not induce a reactive phenotype in either cortical or spinal cord astrocytes. Finally, astrocytes were co-cultured with dorsal root ganglia to determine how the surfaces affected astrocyte-mediated neurite outgrowth. Astrocytes cultured on the fibers for shorter periods of time (1 day) generally supported longer neurite outgrowth. Pitted and divoted fibers restricted spinal cord astrocyte-mediated neurite outgrowth, while smooth fibers increased 3 day spinal cord astrocyte-mediated neurite outgrowth. In total, fiber surface nanotopography can influence astrocyte elongation and influence the capability of astrocytes to direct neurites. Therefore, fiber surface characteristics should be carefully controlled to optimize astrocyte-mediated axonal

  9. Regulation of chick bone growth by leptin and catecholamines.

    Science.gov (United States)

    Mauro, L J; Wenzel, S J; Sindberg, G M

    2010-04-01

    neurotransmitters may facilitate this by promoting chondrocyte maturation. These studies represent novel evidence suggesting a role of sympathetic tone in the regulation of skeletal growth in avian species.

  10. Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth.

    Science.gov (United States)

    Koppes, Abigail N; Nordberg, Andrea L; Paolillo, Gina M; Goodsell, Nicole M; Darwish, Haley A; Zhang, Linxia; Thompson, Deanna M

    2014-02-01

    Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite outgrowth and a more pronounced effect was observed if both peripheral glia (Schwann cells) and neurons were co-stimulated. If electrical stimulation is delivered to an injury site, both the neurons and all resident non-neuronal cells [e.g., Schwann cells, endothelial cells, fibroblasts] will be treated and this biophysical stimuli can influence axonal growth directly or indirectly via changes to the resident, non-neuronal cells. In this work, non-neuronal cells were electrically stimulated, and changes in morphology and neuro-supportive cells were evaluated. Schwann cell response (morphology and orientation) was examined after an 8 h stimulation over a range of DC fields (0-200 mV/mm, DC 1 mA), and changes in orientation were observed. Electrically prestimulating Schwann cells (50 mV/mm) promoted 30% more neurite outgrowth relative to co-stimulating both Schwann cells with neurons, suggesting that electrical stimulation modifies Schwann cell phenotype. Conditioned medium from the electrically prestimulated Schwann cells promoted a 20% increase in total neurite outgrowth and was sustained for 72 h poststimulation. An 11-fold increase in nerve growth factor but not brain-derived neurotrophic factor or glial-derived growth factor was found in the electrically prestimulated Schwann cell-conditioned medium. No significant changes in fibroblast or endothelial morphology and neuro-supportive behavior were observed poststimulation. Electrical stimulation is widely used in

  11. the role of plant growth regulators in morphogenesis

    Directory of Open Access Journals (Sweden)

    A. Mujib

    2018-01-01

    Full Text Available Althaea officinalis L. (marshmallow belonging to the Malvaceae family, is an important plant that contains a variety of important phytocompounds including asparagine, pectin, flavonoids, polyphenolic acid, and scopoletin. The yield of these compounds can be improved using biotechnological methods that allow for a steady and continuous regeneration of plant material. To the best of our knowledge, thus far, the In vitro clonal multiplication of marshmallow has not been attempted on a large scale. Therefore, in this study, we developed callus induction and multiple shoot regeneration protocols from explants. All the explants, i.e., roots, nodes, and leaves, evoked compact white or yellow calli in a medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D, which grew vigorously. The callus induction frequency was the highest (62.1% from stem nodes, followed by leaves (39.1% and roots (27.5%. The differential behavior of explants in response to various plant growth regulators (PGRs was studied. The calli from leaves and roots were noted to be non-organogenic/embryogenic in media containing different PGR concentrations and have been described in this communication. The stem nodes used were cultured on MS media amended with different concentrations of benzyl-amino-purine (BAP: 0.5, 1.0, and 2.0 mg/l. Multiple shoots were formed at variable numbers, the maximum being in a medium supplemented with 1.0 mg/l of BAP. The induced shoots were rooted in IBA-, NAA-, and IAA-amended media, where IBA at 0.5 mg/l induced a maximum number of roots (8.8 roots/shoot. The regenerated plants were transferred to plastic pots, filled with soilrite and soil (1 : 1, and finally, transferred to outdoor conditions.

  12. Developmental regulation of human truncated nerve growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. (Abbott Laboratories, Abbott Park, IL (USA))

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  13. Developmental regulation of human truncated nerve growth factor receptor

    International Nuclear Information System (INIS)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R.

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system

  14. Vegetative growth response of cotton plants due to growth regulator supply via seeds

    Directory of Open Access Journals (Sweden)

    João Vitor Ferrari

    2015-08-01

    Full Text Available The global cotton industry is distinguished by its numerous industrial uses of the plume as well as by high production costs. Excessive vegetative growth can interfere negatively with productivity, and thus, applying growth regulators is essential for the development of the cotton culture. The objective of this study was to evaluate the development and yield of the cotton cultivar FMT 701 with the application of mepiquat chloride to seeds and leaves. The experimental design used a randomized block design with four replications, arranged in bands.The treatments consisted of mepiquat chloride rates (MC (0, 4, 6, 8 and 10 g a.i. kg-1 of seeds applied directly to the cotton seeds and MC management by foliar spray using a 250 mL ha-1 rates that was administered under the following conditions: divided into four applications (35, 45, 55 and 65 days after emergence; as a single application at 70 days; and without the application of the product. The mepiquat chloride applied to cotton seeds controls the initial plant height and stem diameter, while foliar application reduces the height of the plants. After application to seed, foliar spraying MC promotes increase mass of 20 bolls, however no direct influence amount bolls per plant and yield of cotton seed. Higher cotton seed yield was obtained with a rate of 3.4 g a.i. MC kg-1 seeds.

  15. Effects of growth regulator herbicide on downy brome (Bromus tectorum) seed production

    Science.gov (United States)

    Previous research showed growth regulator herbicides, such as picloram and aminopyralid, have a sterilizing effect on Japanese brome (Bromus japonicus Thunb.) that can reduce this invasive annual grass’s seed production nearly 100%. This suggests growth regulators might be used to control invasive ...

  16. Effects of plant growth regulators on callus, shoot and root formation ...

    African Journals Online (AJOL)

    Root and stem explants of fluted pumpkin were cultured in medium containing different types and concentrations of plant growth regulators (PGRs). The explants were observed for callus, root and shoot formation parameters after four months. Differences among explants, plant growth regulators and their interaction were ...

  17. The effect of some growth regulators on enzyme systems in irradiated barley grain using disinfestation doses

    International Nuclear Information System (INIS)

    Bachman, S.

    1973-01-01

    Disinfestation doses of 20 to 100 krad may cause changes in the biological systems of barley grain and, therefore, may influence undesirably the technological quality of malted grain. The effect of some growth regulators on irradiated grain has been investigated. The experiments have been carried out on brewery barley var. Visa Breuns. Following growth-regulators were used: gibberellic acid (Polish preparation ''Gibrescol''), kinetin (6-furfurylo-aminopurin), CCC (2-chloroethyl trimethyl ammonium chloride), and betaine hydrochloride. By treating the irradiated barley with solutions of growth regulators it was possible to diminish the loss of enzyme activity. A ''regenerating'' effect of growth substances, mainly gibberellic acid and betain hydrochloride in 10 -4 M solutions, was observed. Amylolytic activity decreased immediately after irradiation but in samples treated with growth regulators it was higher than in those without regulators. The results may have a practical importance since gibberellic acid has just been introduced into the brewery industry. (F.J.)

  18. Hormonal regulation of wheat growth during hydroponic culture

    Science.gov (United States)

    Wetherell, Donald

    1988-01-01

    Hormonal control of root growth has been explored as one means to alleviate the crowding of plant root systems experienced in prototype hydroponic biomass production chambers being developed by the CELSS Breadboard Project. Four plant hormones, or their chemical analogs, which have been reported to selectively inhibit root growth, were tested by adding them to the nutrient solutions on day 10 of a 25 day growth test using spring wheat in hydroponic cultures. Growth and morphological changes is both shoot and root systems were evaluated. In no case was it possible to inhibit root growth without a comparable inhibition of shoot growth. It was concluded that this approach is unlikely to prove useful for wheat.

  19. Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields

    Science.gov (United States)

    Koppes, Abigail N.; Seggio, Angela M.; Thompson, Deanna M.

    2011-08-01

    Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm-1). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm-1, and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm-1 electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm-1 dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

  20. Enhanced differentiation of neural stem cells to neurons and promotion of neurite outgrowth by oxygen-glucose deprivation.

    Science.gov (United States)

    Wang, Qin; Yang, Lin; Wang, Yaping

    2015-06-01

    Stroke has become the leading cause of mortality worldwide. Hypoxic or ischemic insults are crucial factors mediating the neural damage in the brain tissue of stroke patients. Neural stem cells (NSCs) have been recognized as a promising tool for the treatment of ischemic stroke and other neurodegenerative diseases due to their inducible pluripotency. In this study, we aim to mimick the cerebral hypoxic-ischemic injury in vitro using oxygen-glucose deprivation (OGD) strategy, and evaluate the effects of OGD on the NSC's neural differentiation, as well as the differentiated neurite outgrowth. Our data showed that NSCs under the short-term 2h OGD treatment are able to maintain cell viability and the capability to form neurospheres. Importantly, this moderate OGD treatment promotes NSC differentiation to neurons and enhances the performance of the mature neuronal networks, accompanying increased neurite outgrowth of differentiated neurons. However, long-term 6h and 8h OGD exposures in NSCs lead to decreased cell survival, reduced differentiation and diminished NSC-derived neurite outgrowth. The expressions of neuron-specific microtubule-associated protein 2 (MAP-2) and growth associated protein 43 (GAP-43) are increased by short-term OGD treatments but suppressed by long-term OGD. Overall, our results demonstrate that short-term OGD exposure in vitro induces differentiation of NSCs while maintaining their proliferation and survival, providing valuable insights of adopting NSC-based therapy for ischemic stroke and other neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway.

    Science.gov (United States)

    Chen, Hongbin; Lin, Wei; Zhang, Yixian; Lin, Longzai; Chen, Jianhao; Zeng, Yongping; Zheng, Mouwei; Zhuang, Zezhong; Du, Houwei; Chen, Ronghua; Liu, Nan

    2016-07-26

    As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemia in vivo or oxygen-glucose deprivation (OGD)-induced injury in vitro. However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury. We found that IL-10 treatment activated the Janus kinase 1 (JAK1)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. Moreover, IL-10 attenuated OGD-induced neuronal apoptosis by down-regulating the Bax expression and up-regulating the Bcl-2 expression, facilitated neurite outgrowth by increasing the expression of Netrin-1, and promoted synapse formation in cultured primary cortical neurons after OGD injury. These effects were partly abolished by JAK1 inhibitor GLPG0634. Contrarily, IL-10NA produced opposite effects on the cultured cortical neurons after OGD injury. Taken together, our findings suggest that IL-10 not only attenuates neuronal apoptosis, but also promotes neurite outgrowth and synapse formation via the JAK1/STAT3 signaling pathway in cultured primary cortical neurons after OGD injury.

  2. [Inhibitory proteins of neuritic regeneration in the extracellular matrix: structure, molecular interactions and their functions. Mechanisms of extracellular balance].

    Science.gov (United States)

    Vargas, Javier; Uribe-Escamilla, Rebeca; Alfaro-Rodríguez, Alfonso

    2013-01-01

    After injury of the central nervous system (CNS) in higher vertebrates, neurons neither grow nor reconnect with their targets because their axons or dendrites cannot regenerate within the injured site. In the CNS, the signal from the environment regulating neurite regeneration is not exclusively generated by one molecular group. This signal is generated by the interaction of various types of molecules such as extracellular matrix proteins, soluble factors and surface membrane molecules; all these elements interact with one another generating the matrix's biological state: the extracellular balance. Proteins in the balanced extracellular matrix, support and promote cellular physiological states, including neuritic regeneration. We have reviewed three types of proteins of the extracellular matrix possessing an inhibitory effect and that are determinant of neuritic regeneration failure in the CNS: chondroitin sulfate proteoglycans, keratan sulfate proteoglycans and tenascin. We also review some of the mechanisms involved in the balance of extracellular proteins such as isomerization, epimerization, sulfation and glycosylation as well as the assemblage of the extracellular matrix, the interaction between the matrix and soluble factors and its proteolytic degradation. In the final section, we have presented some examples of the matrix's role in development and in tumor propagation.

  3. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  4. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  5. NOGO-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition

    Directory of Open Access Journals (Sweden)

    Liwnicz Boleslaw H

    2007-04-01

    Full Text Available Abstract Background Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS and may play a role in maintaining neural pathways once established. However, the presence of Nogo-A during early CNS development is counterintuitive and hints at an additional role for Nogo-A beyond neurite inhibition. Results We isolated chicken NOGO-A and determined its sequence. A multiple alignment of the amino acid sequence across divergent species, identified five previously undescribed, Nogo-A specific conserved regions that may be relevant for development. NOGO gene transcripts (NOGO-A, NOGO-B and NOGO-C were differentially expressed in the CNS during development and a second NOGO-A splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by in situ hybridization. CNS-associated NOGO-A was induced coincident with neural plate formation and up-regulated by FGF in the transformation of non-neural ectoderm into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during the early proliferative phase of development, and migration, but localized to large projection neurons of the optic tectum and tectal-associated nuclei during architectural differentiation, lamination and network establishment. Conclusion These data suggest Nogo-A plays a functional role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis. These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS.

  6. ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

    Science.gov (United States)

    Lievens, Patricia Marie-Jeanne; Kuznetsova, Tatiana; Kochlamazashvili, Gaga; Cesca, Fabrizia; Gorinski, Natalya; Galil, Dalia Abdel; Cherkas, Volodimir; Ronkina, Natalia; Lafera, Juri; Gaestel, Matthias

    2016-01-01

    The neural cell adhesion molecule (NCAM) mediates cell-cell and cell-matrix adhesion. It is broadly expressed in the nervous system and regulates neurite outgrowth, synaptogenesis, and synaptic plasticity. Previous in vitro studies revealed that palmitoylation of NCAM is required for fibroblast growth factor 2 (FGF2)-stimulated neurite outgrowth and identified the zinc finger DHHC (Asp-His-His-Cys)-containing proteins ZDHHC3 and ZDHHC7 as specific NCAM-palmitoylating enzymes. Here, we verified that FGF2 controlled NCAM palmitoylation in vivo and investigated molecular mechanisms regulating NCAM palmitoylation by ZDHHC3. Experiments with overexpression and pharmacological inhibition of FGF receptor (FGFR) and Src revealed that these kinases control tyrosine phosphorylation of ZDHHC3 and that ZDHHC3 is phosphorylated by endogenously expressed FGFR and Src proteins. By site-directed mutagenesis, we found that Tyr18 is an FGFR1-specific ZDHHC3 phosphorylation site, while Tyr295 and Tyr297 are specifically phosphorylated by Src kinase in cell-based and cell-free assays. Abrogation of tyrosine phosphorylation increased ZDHHC3 autopalmitoylation, enhanced interaction with NCAM, and upregulated NCAM palmitoylation. Expression of ZDHHC3 with tyrosine mutated in cultured hippocampal neurons promoted neurite outgrowth. Our findings for the first time highlight that FGFR- and Src-mediated tyrosine phosphorylation of ZDHHC3 modulates ZDHHC3 enzymatic activity and plays a role in neuronal morphogenesis. PMID:27247265

  7. Neurite outgrowth in human iPSC-derived neurons

    Science.gov (United States)

    Data on morphology of rat and human neurons in cell cultureThis dataset is associated with the following publication:Druwe, I., T. Freudenrich , K. Wallace , T. Shafer , and W. Mundy. Comparison of Human Induced PluripotentStem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth. Applied In vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).

  8. Growth rate regulated genes and their wide involvement in the Lactococcus lactis stress responses

    Directory of Open Access Journals (Sweden)

    Redon Emma

    2008-07-01

    Full Text Available Abstract Background The development of transcriptomic tools has allowed exhaustive description of stress responses. These responses always superimpose a general response associated to growth rate decrease and a specific one corresponding to the stress. The exclusive growth rate response can be achieved through chemostat cultivation, enabling all parameters to remain constant except the growth rate. Results We analysed metabolic and transcriptomic responses of Lactococcus lactis in continuous cultures at different growth rates ranging from 0.09 to 0.47 h-1. Growth rate was conditioned by isoleucine supply. Although carbon metabolism was constant and homolactic, a widespread transcriptomic response involving 30% of the genome was observed. The expression of genes encoding physiological functions associated with biogenesis increased with growth rate (transcription, translation, fatty acid and phospholipids metabolism. Many phages, prophages and transposon related genes were down regulated as growth rate increased. The growth rate response was compared to carbon and amino-acid starvation transcriptomic responses, revealing constant and significant involvement of growth rate regulations in these two stressful conditions (overlap 27%. Two regulators potentially involved in the growth rate regulations, llrE and yabB, have been identified. Moreover it was established that genes positively regulated by growth rate are preferentially located in the vicinity of replication origin while those negatively regulated are mainly encountered at the opposite, thus indicating the relationship between genes expression and their location on chromosome. Although stringent response mechanism is considered as the one governing growth deceleration in bacteria, the rigorous comparison of the two transcriptomic responses clearly indicated the mechanisms are distinct. Conclusion This work of integrative biology was performed at the global level using transcriptomic analysis

  9. Warts signaling controls organ and body growth through regulation of ecdysone

    DEFF Research Database (Denmark)

    Møller, Morten Erik; Nagy, Stanislav; Gerlach, Stephan Uwe

    2017-01-01

    Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms...... under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin....../insulin-like growth factor (IGF) (insulin) signaling [2, 5]. The interplay between insulin and ecdysone signaling regulates systemic growth and controls organismal size. Here, we show that Warts (Wts; LATS1/2) signaling regulates systemic growth in Drosophila by activating basal ecdysone production, which negatively...

  10. Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

    Directory of Open Access Journals (Sweden)

    Heiko Löhr

    2018-05-01

    Full Text Available Summary: Anorexigenic pro-opiomelanocortin (Pomc/alpha-melanocyte stimulating hormone (αMSH neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful. : The melanocortin system controls energy homeostasis and somatic growth, but the underlying mechanisms are elusive. Löhr et al. identify a functional neural circuit in which Pomc neurons stimulate hypothalamic somatostatin neurons, thereby inhibiting hypophyseal growth hormone production. Excessive feeding and acquired leptin resistance attenuate this pathway, allowing faster somatic growth when food resources are rich. Keywords: Pomc neuron, somatostatin neuron, somatic growth, growth hormone, melanocortin system, high-fat diet, obesity, leptin resistance, zebrafish, mouse

  11. Methods for growth regulation of greenhouse produced ornamental pot- and bedding plants – a current review

    Directory of Open Access Journals (Sweden)

    Bergstrand Karl-Johan I.

    2017-06-01

    Full Text Available Chemical plant growth regulators (PGRs are used in the production of ornamental potted and bedding plants. Growth control is needed for maximizing production per unit area, reducing transportation costs and to obtain a desired visual quality. However, the use of PGRs is associated with toxicity risks to humans and the environment. In many countries the availability of PGRs is restricted as few substances are registered for use. A number of alternative methods have been suggested. The methods include genetic methods (breeding and crop cultivation practices such as fertigation, temperature and light management. A lot of research into “alternative” growth regulation was performed during the 1980-1990s, revealing several possible ways of using different climatic factors to optimize plant growth with respect to plant height. In recent years, the interest in climatic growth regulation has been resurrected, not least due to the coming phase-out of the plant growth regulator chlormequat chloride (CCC. Today, authorities in many countries are aiming towards reducing the use of agrochemicals. At the same time, there is a strong demand from consumers for products produced without chemicals. This article provides a broad overview of available methods for non-chemical growth control. It is concluded that a combination of plant breeding and management of temperature, fertigation and light management has the potential of replacing chemical growth regulators in the commercial production of ornamental pot- and bedding plants.

  12. AMPK regulation of the growth of cultured human keratinocytes

    International Nuclear Information System (INIS)

    Saha, Asish K.; Persons, Kelly; Safer, Joshua D.; Luo Zhijun; Holick, Michael F.; Ruderman, Neil B.

    2006-01-01

    AMP kinase (AMPK) is a fuel sensing enzyme that responds to cellular energy depletion by increasing processes that generate ATP and inhibiting others that require ATP but are not acutely necessary for survival. In the present study, we examined the relationship between AMPK activation and the growth (proliferation) of cultured human keratinocytes and assessed whether the inhibition of keratinocyte growth by vitamin D involves AMPK activation. In addition, we explored whether the inhibition of keratinocyte proliferation as they approach confluence could be AMPK-related. Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). At concentrations of 10 -4 and 10 -3 M, AICAR inhibited keratinocyte growth by 50% and 95%, respectively, based on measurements of thymidine incorporation into DNA. It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK activation had occurred. Incubation with the thiazolidinedione, troglitazone (10 -6 M) caused similar alterations in P-AMPK, P-ACC, and cell growth. In contrast, the well known inhibition of keratinocyte growth by 1,25-dihydroxyvitamin D 3 (10 -7 and 10 -6 M) was not associated with changes in P-AMPK or P-ACC. Like most cells, the growth of keratinocytes diminished as they approached confluence. Thus, it was of note that we found a progressive increase in P-AMPK (1.5- to 2-fold, p 3 is AMPK-independent

  13. Information Integration and Communication in Plant Growth Regulation.

    Science.gov (United States)

    Chaiwanon, Juthamas; Wang, Wenfei; Zhu, Jia-Ying; Oh, Eunkyoo; Wang, Zhi-Yong

    2016-03-10

    Plants are equipped with the capacity to respond to a large number of diverse signals, both internal ones and those emanating from the environment, that are critical to their survival and adaption as sessile organisms. These signals need to be integrated through highly structured intracellular networks to ensure coherent cellular responses, and in addition, spatiotemporal actions of hormones and peptides both orchestrate local cell differentiation and coordinate growth and physiology over long distances. Further, signal interactions and signaling outputs vary significantly with developmental context. This review discusses our current understanding of the integrated intracellular and intercellular signaling networks that control plant growth. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Anisotropic cell growth-regulated surface micropatterns in flower petals

    Directory of Open Access Journals (Sweden)

    Xiao Huang

    2017-05-01

    Full Text Available Flower petals have not only diverse macroscopic morphologies but are rich in microscopic surface patterns, which are crucial to their biological functions. Both experimental measurements and theoretical analysis are conducted to reveal the physical mechanisms underlying the formation of minute wrinkles on flower petals. Three representative flowers, daisy, kalanchoe blossfeldiana, and Eustoma grandiflorum, are investigated as examples. A surface wrinkling model, incorporating the measured mechanical properties and growth ratio, is used to elucidate the difference in their surface morphologies. The mismatch between the anisotropic epidermal cell growth and the isotropic secretion of surficial wax is found to dictate the surface patterns.

  15. Cellular growth in plants requires regulation of cell wall biochemistry.

    Science.gov (United States)

    Chebli, Youssef; Geitmann, Anja

    2017-02-01

    Cell and organ morphogenesis in plants are regulated by the chemical structure and mechanical properties of the extracellular matrix, the cell wall. The two primary load bearing components in the plant cell wall, the pectin matrix and the cellulose/xyloglucan network, are constantly remodelled to generate the morphological changes required during plant development. This remodelling is regulated by a plethora of loosening and stiffening agents such as pectin methyl-esterases, calcium ions, expansins, and glucanases. The tight spatio-temporal regulation of the activities of these agents is a sine qua non condition for proper morphogenesis at cell and tissue levels. The pectin matrix and the cellulose-xyloglucan network operate in concert and their behaviour is mutually dependent on their chemical, structural and mechanical modifications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.

    Directory of Open Access Journals (Sweden)

    Anupama Yadav

    Full Text Available The ability of a genotype to show diverse phenotypes in different environments is called phenotypic plasticity. Phenotypic plasticity helps populations to evade extinctions in novel environments, facilitates adaptation and fuels evolution. However, most studies focus on understanding the genetic basis of phenotypic regulation in specific environments. As a result, while it's evolutionary relevance is well established, genetic mechanisms regulating phenotypic plasticity and their overlap with the environment specific regulators is not well understood. Saccharomyces cerevisiae is highly sensitive to the environment, which acts as not just external stimulus but also as signalling cue for this unicellular, sessile organism. We used a previously published dataset of a biparental yeast population grown in 34 diverse environments and mapped genetic loci regulating variation in phenotypic plasticity, plasticity QTL, and compared them with environment-specific QTL. Plasticity QTL is one whose one allele exhibits high plasticity whereas the other shows a relatively canalised behaviour. We mapped phenotypic plasticity using two parameters-environmental variance, an environmental order-independent parameter and reaction norm (slope, an environmental order-dependent parameter. Our results show a partial overlap between pleiotropic QTL and plasticity QTL such that while some plasticity QTL are also pleiotropic, others have a significant effect on phenotypic plasticity without being significant in any environment independently. Furthermore, while some plasticity QTL are revealed only in specific environmental orders, we identify large effect plasticity QTL, which are order-independent such that whatever the order of the environments, one allele is always plastic and the other is canalised. Finally, we show that the environments can be divided into two categories based on the phenotypic diversity of the population within them and the two categories have

  17. Institutions and Regulation for Economic Growth ? : public interests versus public incentives

    NARCIS (Netherlands)

    Wubben, E.F.M.

    2011-01-01

    Realizing institutions and regulations that foster economic growth is an essential asset for contemporary economies. This book investigates practices and options for steering individual and firm behaviour that prevents unacceptable externalities and boosts public interests. These multi-dimensional

  18. Orchestrated structure evolution: modeling growth-regulated nanomanufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Shaghayegh; Boehringer, Karl F [Department of Electrical Engineering, University of Washington, Seattle, WA 98195-2500 (United States); Kitayaporn, Sathana; Schwartz, Daniel T, E-mail: karlb@washington.edu [Department of Chemical Engineering, University of Washington, Seattle, WA 98195-2500 (United States)

    2011-04-22

    Orchestrated structure evolution (OSE) is a scalable manufacturing method that combines the advantages of top-down (tool-directed) and bottom-up (self-propagating) approaches. The method consists of a seed patterning step that defines where material nucleates, followed by a growth step that merges seeded islands into the final patterned thin film. We develop a model to predict the completed pattern based on a computationally efficient approximate Green's function solution of the diffusion equation plus a Voronoi diagram based approach that defines the final grain boundary structure. Experimental results rely on electron beam lithography to pattern the seeds, followed by the mass transfer limited growth of copper via electrodeposition. The seed growth model is compared with experimental results to quantify nearest neighbor seed-to-seed interactions as well as how seeds interact with the pattern boundary to impact the local growth rate. Seed-to-seed and seed-to-pattern interactions are shown to result in overgrowth of seeds on edges and corners of the shape, where seeds have fewer neighbors. We explore how local changes to the seed location can be used to improve the patterning quality without increasing the manufacturing cost. OSE is shown to enable a unique set of trade-offs between the cost, time, and quality of thin film patterning.

  19. Regulation of the growth and photosynthesis of cherry tomato ...

    African Journals Online (AJOL)

    The growth and photosynthetic characteristics of cherry tomato seedlings were investigated under seven light irradiations such as dysprosium lamps (white light; control, C), red light emitting diodes (LEDs) (R), blue LEDs (B), orange LEDs (O), green LEDs (G), red and blue LEDs (RB) and red, blue and green LEDs (RBG) ...

  20. Effect of temperature, light intensity and growth regulators on ...

    African Journals Online (AJOL)

    Ansellia africana (Orchidaceae) is an important endangered medicinal plant species of South Africa which has been heavily exploited in recent years. Experiments were conducted in growth rooms at different temperatures (16, 26, 36°C) and in a nursery at different light intensities induced by shade cloth densities (200, 400, ...

  1. Influence of plant growth regulators on development and ...

    African Journals Online (AJOL)

    Therefore propagation of the plant material by cell cultures and the extraction of potential pharmaceutical active compounds are of great interest. Calli were established on different media from roots and shoots of seedlings and softness and colour of the tissue were compared. Optimum growth of callus cultures was ...

  2. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  3. Analysis of the Yeast Kinome Reveals a Network of Regulated Protein Localization during Filamentous Growth

    OpenAIRE

    Bharucha, Nikë; Ma, Jun; Dobry, Craig J.; Lawson, Sarah K.; Yang, Zhifen; Kumar, Anuj

    2008-01-01

    The subcellular distribution of kinases and other signaling proteins is regulated in response to cellular cues; however, the extent of this regulation has not been investigated for any gene set in any organism. Here, we present a systematic analysis of protein kinases in the budding yeast, screening for differential localization during filamentous growth. Filamentous growth is an important stress response involving mitogen-activated protein kinase and cAMP-dependent protein kinase signaling m...

  4. Foliar fertilizations with boron and growth regulators on lettuce (Lactuca sativa L.) cv floresta culture

    International Nuclear Information System (INIS)

    Masunaga, S.I.; Chueire, F.B.; Teixeira, N.T.

    1989-01-01

    The experiment was realized to verify the possibility of applying Boron as foliar fertilization with growth regulators: indol acetic acid, giberellic acid, ethephon and cycocel. The other objective was to compare the foliar and soil fertilization, with Boron, on the lettuce culture. The results showed that there wasn't difference of production between the treatments. Meanwhile the application of growth regulator modified the Boron grade in the leaves. (author) [pt

  5. Regulation of growth and nutrient uptake under different transpiration regimes

    NARCIS (Netherlands)

    Amor, del F.M.; Marcelis, L.F.M.

    2005-01-01

    To determine the extent to which air humidity affects the regulation of nutrient demand, an experiment with tomato plants was carried out under fully controlled climate conditions. Treatments consisted of three levels of relative air humidity (RH): 50%, 70% (control) and 95%, corresponding to 1.32,

  6. Crop growth, light utilization and yield of relay intercropped cotton as affected by plant density and a plant growth regulator

    NARCIS (Netherlands)

    Mao, L.; Zhang, L.; Zhao, X.; Liu, S.; Werf, van der W.; Zhang, S.; Spiertz, J.H.J.; Li, Z.

    2014-01-01

    Modern cotton cultivation requires high plant densities and compact plants. Here we study planting density and growth regulator effects on plant structure and production of cotton when the cotton is grown in a relay intercrop with wheat, a cultivation system that is widespread in China. Field

  7. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  8. Growth Hormone Receptor Signaling Pathways and its Negative Regulation by SOCS2

    DEFF Research Database (Denmark)

    Fernández Pérez, Leandro; Flores-Morales, Amilcar; Guerra, Borja

    2016-01-01

    Growth hormone (GH) is a critical regulator of linear body growth during childhood but continues to have important metabolic actions throughout life. The GH receptor (GHR) is ubiquitously expressed, and deficiency of GHR signaling causes a dramatic impact on normal physiology during somatic devel...

  9. Effect of plant growth regulators on in vitro germination of coffee ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Germination times of zygotic embryos cultured in MS medium had a mean of 5.1 days, ... growth regulators used, gibberellic acid at 0.1 mg l-1 proved to be the most efficient in .... process, and the biological role of regulators was invest- ... thiamine, 25 mg l-1 cysteine, and 3% sucrose for MS; and 100 mg l-1.

  10. Using natural and synthetic growth regulators of plants in industrial mycology and malting

    Directory of Open Access Journals (Sweden)

    O. V. Kuznetcova

    2010-07-01

    Full Text Available Data on the expansion of the use the plants growth regulators in different areas are presented. The positive impact of the growth stimulators on the development of the Pleurotus ostreatus mycelium’s on agar nutrient media during surface cultivation is shown. The results for growth regulators stimulating effect on the fungus biosynthetic activity in submerged cultures are obtained. The possibility of using fumar and heteroauxin for malting is considered. The decline of malting time and increase of amylolytic activity of the malt are recorded.

  11. Regulation of Long Bone Growth in Vertebrates; It Is Time to Catch Up.

    Science.gov (United States)

    Roselló-Díez, Alberto; Joyner, Alexandra L

    2015-12-01

    The regulation of organ size is essential to human health and has fascinated biologists for centuries. Key to the growth process is the ability of most organs to integrate organ-extrinsic cues (eg, nutritional status, inflammatory processes) with organ-intrinsic information (eg, genetic programs, local signals) into a growth response that adapts to changing environmental conditions and ensures that the size of an organ is coordinated with the rest of the body. Paired organs such as the vertebrate limbs and the long bones within them are excellent models for studying this type of regulation because it is possible to manipulate one member of the pair and leave the other as an internal control. During development, growth plates at the end of each long bone produce a transient cartilage model that is progressively replaced by bone. Here, we review how proliferation and differentiation of cells within each growth plate are tightly controlled mainly by growth plate-intrinsic mechanisms that are additionally modulated by extrinsic signals. We also discuss the involvement of several signaling hubs in the integration and modulation of growth-related signals and how they could confer remarkable plasticity to the growth plate. Indeed, long bones have a significant ability for "catch-up growth" to attain normal size after a transient growth delay. We propose that the characterization of catch-up growth, in light of recent advances in physiology and cell biology, will provide long sought clues into the molecular mechanisms that underlie organ growth regulation. Importantly, catch-up growth early in life is commonly associated with metabolic disorders in adulthood, and this association is not completely understood. Further elucidation of the molecules and cellular interactions that influence organ size coordination should allow development of novel therapies for human growth disorders that are noninvasive and have minimal side effects.

  12. Hormonal regulation of the growth of leaves and inflorescence stalk in Muscari armeniacum Leichtl.

    Directory of Open Access Journals (Sweden)

    Marian Saniewski

    2016-04-01

    Full Text Available It is known that chilling of Muscari bulbs is necessary for the growth of the inflorescence stalk and flowering, but not for the growth of leaves. Gibberellic acid (GA accelerated stem growth and flowering in chilled Muscari bulbs. In the present experiment it was shown that in unchilled derooted Muscari bulbs the growth of leaves, but not the growth of the inflorescence stalk, was observed when bulbs were stored in water, GA at a concentration of 50 and 100 mg/L, benzyladenine (BA at a concentration of 25 and 50 mg/L, or a mixture of GA+BA (50+25 mg/L, but abscisic acid (ABA at a concentration of 10 mg/L greatly inhibited the growth of leaves. In chilled derooted Muscari bulbs the growth of leaves and inflorescence stalk was observed when bulbs were stored in water or GA, but BA and GA+BA treatments totally inhibited the growth of the inflorescence stalk without an effect on the growth of leaves. These results clearly showed that the growth of leaves and inflorescence stalk in Muscari bulbs are controlled by plant growth regulators in different ways. ABA totally inhibited the growth of leaves and inflorescence stalk in chilled derooted Muscari bulbs. It was shown that after the excision of the inflorescence bud in cultivated chilled Muscari bulbs, the inflorescence stalk died, but application of indole-3-acetic acid (IAA 0.5% in the place of the removed inflorescence bud induced the growth of the inflorescence stalk. IAA applied under the inflorescence bud inhibited the development of flowers (flower-bud blasting and induced the growth of the inflorescence stalk below the treatment site. These results are discussed with reference to hormonal regulation of stem (stalk growth in tulip, narcissus, hyacinth, and Hippeastrum.

  13. GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

    Science.gov (United States)

    Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

    2015-07-29

    The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

  14. The regulation of cell growth and survival by aldosterone.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2012-02-01

    The steroid hormone aldosterone is synthesized from cholesterol, mainly in the zona glomerulosa of the adrenal cortex. Aldosterone exerts its effects in the epithelial tissues of the kidney and colon and in non-epithelial tissues such as the brain and cardiovasculature. The genomic response to aldosterone involves dimerization of the mineralocorticoid receptor (MR), dissociation of heat shock proteins from MR, translocation of the aldosterone-MR complex to the nucleus and the concomitant regulation of gene expression. Rapid responses to aldosterone occur within seconds to minutes, do not involve transcription or translation and can modulate directly or indirectly the later genomic responses. Aside from the well-known effects of aldosterone on the regulation of sodium and water homeostasis, aldosterone can also produce deleterious structural changes in tissues by inducing hypertrophy and the dysregulation of proliferation and apoptosis, leading to fibrosis and tissue remodelling. Here we discuss the involvement of aldosterone-mediated rapid signalling cascades in the development of disease states such as chronic kidney disease and heart failure, and the antagonists that can inhibit these pathophysiological responses.

  15. The regulation of cell growth and survival by aldosterone.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-01-01

    The steroid hormone aldosterone is synthesized from cholesterol, mainly in the zona glomerulosa of the adrenal cortex. Aldosterone exerts its effects in the epithelial tissues of the kidney and colon and in non-epithelial tissues such as the brain and cardiovasculature. The genomic response to aldosterone involves dimerization of the mineralocorticoid receptor (MR), dissociation of heat shock proteins from MR, translocation of the aldosterone-MR complex to the nucleus and the concomitant regulation of gene expression. Rapid responses to aldosterone occur within seconds to minutes, do not involve transcription or translation and can modulate directly or indirectly the later genomic responses. Aside from the well-known effects of aldosterone on the regulation of sodium and water homeostasis, aldosterone can also produce deleterious structural changes in tissues by inducing hypertrophy and the dysregulation of proliferation and apoptosis, leading to fibrosis and tissue remodelling. Here we discuss the involvement of aldosterone-mediated rapid signalling cascades in the development of disease states such as chronic kidney disease and heart failure, and the antagonists that can inhibit these pathophysiological responses.

  16. Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

    Directory of Open Access Journals (Sweden)

    Rodrigo Herrera-Molina

    Full Text Available Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(Vβ(3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(Vβ(3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(Vβ(3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(Vβ(3 integrin restricted neurite outgrowth. Likewise, α(Vβ(3-Fc was sufficient to suppress neurite extension in Thy-1(+, but not in Thy-1(- CAD cells. In differentiating primary neurons exposed to α(Vβ(3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC. Moreover, α(Vβ(3-Fc also induced retraction of already extended Thy-1(+-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(Vβ(3 integrin. Binding of α(Vβ(3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(Vβ(3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(Vβ(3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

  17. Proteomic analysis of differentiating neuroblastoma cells treated with sub-lethal neurite inhibitory concentrations of diazinon: Identification of novel biomarkers of effect

    International Nuclear Information System (INIS)

    Harris, W.; Sachana, M.; Flaskos, J.; Hargreaves, A.J.

    2009-01-01

    In previous work we showed that sub-lethal levels of diazinon inhibited neurite outgrowth in differentiating N2a neuroblastoma cells. Western blotting analysis targeted at proteins involved in axon growth and stress responses, revealed that such exposure led to a reduction in the levels of neurofilament heavy chain, microtubule associated protein 1 B (MAP 1B) and HSP-70. The aim of this study was to apply the approach of 2 dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify novel biomarkers of effect. A number of proteins were found to be up-regulated compared to the control on silver-stained gels. These were classified in to 3 main groups of proteins: cytosolic factors, chaperones and the actin-binding protein cofilin, all of which are involved in cell differentiation, survival or metabolism. The changes observed for cofilin were further confirmed by quantitative Western blotting analysis with anti-actin and anti-cofilin antibodies. Indirect immunofluorescence staining with the same antibodies indicated that the microfilament network was disrupted in diazinon-treated cells. Our data suggest that microfilament organisation is disrupted by diazinon exposure, which may be related to increased cofilin expression.

  18. Regulation of planar growth by the Arabidopsis AGC protein kinase UNICORN.

    Science.gov (United States)

    Enugutti, Balaji; Kirchhelle, Charlotte; Oelschner, Maxi; Torres Ruiz, Ramón Angel; Schliebner, Ivo; Leister, Dario; Schneitz, Kay

    2012-09-11

    The spatial coordination of growth is of central importance for the regulation of plant tissue architecture. Individual layers, such as the epidermis, are clonally propagated and structurally maintained by symmetric cell divisions that are oriented along the plane of the layer. The developmental control of this process is poorly understood. The simple cellular basis and sheet-like structure of Arabidopsis integuments make them an attractive model system to address planar growth. Here we report on the characterization of the Arabidopsis UNICORN (UCN) gene. Analysis of ucn integuments reveals localized distortion of planar growth, eventually resulting in an ectopic multicellular protrusion. In addition, ucn mutants exhibit ectopic growth in filaments and petals, as well as aberrant embryogenesis. We further show that UCN encodes an active AGC VIII kinase. Genetic, biochemical, and cell biological data suggest that UCN suppresses ectopic growth in integuments by directly repressing the KANADI transcription factor ABERRANT TESTA SHAPE. Our findings indicate that UCN represents a unique plant growth regulator that maintains planar growth of integuments by repressing a developmental regulator involved in the control of early integument growth and polarity.

  19. Neto2 Assembles with Kainate Receptors in DRG Neurons during Development and Modulates Neurite Outgrowth in Adult Sensory Neurons.

    Science.gov (United States)

    Vernon, Claire G; Swanson, Geoffrey T

    2017-03-22

    Peripheral sensory neurons in the dorsal root ganglia (DRG) are the initial transducers of sensory stimuli, including painful stimuli, from the periphery to central sensory and pain-processing centers. Small- to medium-diameter non-peptidergic neurons in the neonatal DRG express functional kainate receptors (KARs), one of three subfamilies of ionotropic glutamate receptors, as well as the putative KAR auxiliary subunit Neuropilin- and tolloid-like 2 (Neto2). Neto2 alters recombinant KAR function markedly but has yet to be confirmed as an auxiliary subunit that assembles with and alters the function of endogenous KARs. KARs in neonatal DRG require the GluK1 subunit as a necessary constituent, but it is unclear to what extent other KAR subunits contribute to the function and proposed roles of KARs in sensory ganglia, which include promotion of neurite outgrowth and modulation of glutamate release at the DRG-dorsal horn synapse. In addition, KARs containing the GluK1 subunit are implicated in modes of persistent but not acute pain signaling. We show here that the Neto2 protein is highly expressed in neonatal DRG and modifies KAR gating in DRG neurons in a developmentally regulated fashion in mice. Although normally at very low levels in adult DRG neurons, Neto2 protein expression can be upregulated via MEK/ERK signaling and after sciatic nerve crush and Neto2 -/- neurons from adult mice have stunted neurite outgrowth. These data confirm that Neto2 is a bona fide KAR auxiliary subunit that is an important constituent of KARs early in sensory neuron development and suggest that Neto2 assembly is critical to KAR modulation of DRG neuron process outgrowth. SIGNIFICANCE STATEMENT Pain-transducing peripheral sensory neurons of the dorsal root ganglia (DRG) express kainate receptors (KARs), a subfamily of glutamate receptors that modulate neurite outgrowth and regulate glutamate release at the DRG-dorsal horn synapse. The putative KAR auxiliary subunit Neuropilin- and

  20. Growth regulation in X-irradiated mouse skin

    International Nuclear Information System (INIS)

    Elgjo, K.; Devik, F.

    1978-01-01

    Extracts of hairless mouse skin were tested for their content of epidermal G 1 inhibitor and G 2 inhibitor at daily intervals after X-irradiation with 4 500 or 2 250 rad. After either dose the skin extracts lacked G 1 inhibitory activity on days 5 and 6 respectively after irradiation. This coincided with the time when the epidermal mitotic rate again became normal and started a period of over-shoot. The time interval of 5 to 6 days corresponds to the turnover time of the differentiating cells in hairless mouse back epidermis. The findings indicate that the proliferating cells in epidermis can respond to changes in local chalone concentration, even after X-irradiation at the tested doses, and that the irradiated epidermal cell population still retains some important properties inherent in a cybernetically regulated system. The local G 2 -inhibitory activity also varied after irradiation, but these variations could not be directly related to the corresponding mitotic rates. (author)

  1. A Multilevel Latent Growth Modelling of the Longitudinal Changes in Motivation Regulations in Physical Education

    Directory of Open Access Journals (Sweden)

    Timo Jaakkola

    2015-03-01

    Full Text Available The purpose of this study was to examine individual- and classroom-level differences in the longitudinal change in motivational regulations during physical education students’ transition from elementary (Grade 6 across middle school (Grades 7 to 9. A sample of 757 Finnish adolescents (M = 12.71, SD = 0.23 participated in this study. Participants of the study responded to questionnaires collected six times. A multilevel latent growth modelling approach was used to analyze the data. Results showed that motivational regulations in physical education developed at different rates during middle school. More specifically, students’: (a identified regulation increased across Grades 6 to 9; (b amotivation increased during middle school transition from Grade 6 to 7; and (c introjected regulation declined from Grade 8 to 9. Other motivational regulations remained stable across time. The changes in amotivation and introjected regulation were largely due to individual factors, whereas the changes in identified regulation were due to environmental factors.

  2. Response of pine hypocotyl sections to growth regulators and related substances

    Directory of Open Access Journals (Sweden)

    J. Zakrzewski

    2015-01-01

    Full Text Available Growth response of Pinus silvestris hypocotyl sections to some synthetic growth regulators and related substances was studied. Elongation of hypocotyl sections was stimulated by naphtaleneacetic acid, indole-3-acetic acid, in-dole-3-propionic acid, indole-3-butyric acid, 2,4-dichlorophenoxyacetic acid, indoleaoetic amide, indoleacetic nitrile and coumarin. Indole-3-acetic acid and naphtaleneacetic acid extended period of growth up to 16 and 24 hours, respectively. Growth was inhibited by kinetin, trans-cinnamic acid and 2,3,5-tri-iodobenzoic acid. No effect of gibberellic acid, tryptophan and biotin was observed.

  3. Impact of Growth Hormone on Regulation of Adipose Tissue.

    Science.gov (United States)

    Troike, Katie M; Henry, Brooke E; Jensen, Elizabeth A; Young, Jonathan A; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2017-06-18

    Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output. We will provide an overview of GH structure and function and define several human conditions and cognate mouse lines with extremes in GH action that have helped shape our understanding of GH and AT. A detailed discussion of the GH/AT relationship will be included that addresses adipokine production, immune cell populations, lipid metabolism, senescence, differentiation, and fibrosis, as well as brown AT and beiging of white AT. A brief overview of how GH levels are altered in an obese state, and the efficacy of GH as a therapeutic option to manage obesity will be given. As we will reveal, the effects of GH on AT are numerous, dynamic and depot-dependent. © 2017 American Physiological Society. Compr Physiol 7:819-840, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  4. An Expandable, Inducible Hemangioblast State Regulated by Fibroblast Growth Factor

    Directory of Open Access Journals (Sweden)

    David T. Vereide

    2014-12-01

    Full Text Available During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that “trap” murine cells in a proliferative state and endow them with a hemangioblast potential. These “expandable” hemangioblasts (eHBs are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines.

  5. Transcriptome analysis reveals the regulation of brassinosteroids on petal growth in Gerbera hybrida

    Directory of Open Access Journals (Sweden)

    Gan Huang

    2017-05-01

    Full Text Available Gerbera hybrida is a cut-flower crop of global importance, and an understanding of the mechanisms underlying petal development is vital for the continued commercial development of this plant species. Brassinosteroids (BRs, a class of phytohormones, are known to play a major role in cell expansion, but their effect on petal growth in G. hybrida is largely unexplored. In this study, we found that the brassinolide (BL, the most active BR, promotes petal growth by lengthening cells in the middle and basal regions of petals, and that this effect on petal growth was greater than that of gibberellin (GA. The RNA-seq (high-throughput cDNA sequencing technique was employed to investigate the regulatory mechanisms by which BRs control petal growth. A global transcriptome analysis of the response to BRs in petals was conducted and target genes regulated by BR were identified. These differentially expressed genes (DEGs include various transcription factors (TFs that were activated during the early stage (0.5 h of BL treatment, as well as cell wall proteins whose expression was regulated at a late stage (10 h. BR-responsive DEGs are involved in multiple plant hormone signal pathways, hormone biosynthesis and biotic and abiotic stress responses, showing that the regulation of petal growth by BRs is a complex network of processes. Thus, our study provides new insights at the transcriptional level into the molecular mechanisms of BR regulation of petal growth in G. hybrida.

  6. Integrin β1 regulates leiomyoma cytoskeletal integrity and growth

    Science.gov (United States)

    Malik, Minnie; Segars, James; Catherino, William H.

    2014-01-01

    Uterine leiomyomas are characterized by an excessive extracellular matrix, increased mechanical stress, and increased active RhoA. Previously, we observed that mechanical signaling was attenuated in leiomyoma, but the mechanisms responsible remain unclear. Integrins, especially integrin β1, are transmembrane adhesion receptors that couple extracellular matrix stresses to the intracellular cytoskeleton to influence cell proliferation and differentiation. Here we characterized integrin and laminin to signaling in leiomyoma cells. We observed a 2.25 ± 0.32 fold increased expression of integrin β1 in leiomyoma cells, compared to myometrial cells. Antibody-mediated inhibition of integrin β1 led to significant growth inhibition in leiomyoma cells and a loss of cytoskeletal integrity. Specifically, polymerization of actin filaments and formation of focal adhesions were reduced by inhibition of integrin p1. Inhibition of integrin β1 in leiomyoma cells led to 0.81 ± 0.02 fold decrease in active RhoA, and resembled levels found in serum-starved cells. Likewise, inhibition of integrin β1 was accompanied by a decrease in phospho-ERK. Compared to myometrial cells, leiomyoma cells demonstrated increased expression of integrin α6 subunit to laminin receptor (1.91 ± 0.11 fold), and increased expression of laminin 5α (1.52±0.02), laminin 5β (3.06±0.92), and laminin 5γ (1.66 ± 0.06). Of note, leiomyoma cells grown on laminin matrix appear to realign themselves. Taken together, the findings reveal that the attenuated mechanical signaling in leiomyoma cells is accompanied by an increased expression and a dependence on integrin β1 signaling in leiomyoma cells, compared to myometrial cells. PMID:23023061

  7. Spatial Regulation of Root Growth: Placing the Plant TOR Pathway in a Developmental Perspective

    Science.gov (United States)

    Barrada, Adam; Montané, Marie-Hélène; Robaglia, Christophe; Menand, Benoît

    2015-01-01

    Plant cells contain specialized structures, such as a cell wall and a large vacuole, which play a major role in cell growth. Roots follow an organized pattern of development, making them the organs of choice for studying the spatio-temporal regulation of cell proliferation and growth in plants. During root growth, cells originate from the initials surrounding the quiescent center, proliferate in the division zone of the meristem, and then increase in length in the elongation zone, reaching their final size and differentiation stage in the mature zone. Phytohormones, especially auxins and cytokinins, control the dynamic balance between cell division and differentiation and therefore organ size. Plant growth is also regulated by metabolites and nutrients, such as the sugars produced by photosynthesis or nitrate assimilated from the soil. Recent literature has shown that the conserved eukaryotic TOR (target of rapamycin) kinase pathway plays an important role in orchestrating plant growth. We will summarize how the regulation of cell proliferation and cell expansion by phytohormones are at the heart of root growth and then discuss recent data indicating that the TOR pathway integrates hormonal and nutritive signals to orchestrate root growth. PMID:26295391

  8. Regulation of insulin-like growth factor I receptors on vascular smooth muscle cells by growth factors and phorbol esters.

    Science.gov (United States)

    Ververis, J J; Ku, L; Delafontaine, P

    1993-06-01

    Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells. To characterize regulation of vascular IGF I receptors, we performed radioligand displacement experiments using rat aortic smooth muscle cells (RASMs). Serum deprivation for 48 hours caused a 40% decrease in IGF I receptor number. Exposure of quiescent RASMs to platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), or angiotensin II (Ang II) caused a 1.5-2.0-fold increase in IGF I receptors per cell. After FGF exposure, there was a marked increase in the mitogenic response to IGF I. IGF I downregulated its receptors in the presence of platelet-poor plasma. Stimulation of protein kinase C (PKC) by exposure of quiescent RASMs to phorbol 12-myristate 13-acetate caused a biphasic response in IGF I binding; there was a 42% decrease in receptor number at 45 minutes and a 238% increase at 24 hours. To determine the role of PKC in growth factor-induced regulation of IGF I receptors, we downregulated PKC by exposing RASMs to phorbol 12,13-dibutyrate (PDBu) for 48 hours. PDGF- and FGF- but not Ang II-mediated upregulation of IGF I receptors was completely inhibited in PDBu-treated cells. Thus, acute PKC activation by phorbol esters inhibits IGF I binding, whereas chronic PKC activation increases IGF I binding. PDGF and FGF but not Ang II regulate vascular IGF I receptors through a PKC-dependent pathway. These data provide new insights into the regulation of vascular smooth muscle cell IGF I receptors in vitro and are of potential importance in characterizing vascular proliferative responses in vivo.

  9. EFFECTS OF SOME PLANT GROWTH REGULATORS ON JASMONIC ACID INDUCED INHIBITION OF SEED GERMINATION AND SEEDLING GROWTH OF BARLEY

    Directory of Open Access Journals (Sweden)

    Kürşat ÇAVUŞOĞLU

    2009-02-01

    Full Text Available Abstract: The effects of gibberellic acid, kinetin, benzyladenine, ethylene, 24-epibrassinolide and polyamines (spermine, spermidine, putrescine, cadaverine on jasmonic acid inhibition of seed germination and seedling growth of barley were studied. All of the plant growth regulators studied were determined to have a succesful performance in reversing of the inhibitory effects of jasmonic acid on the seed germination and seedling growth. Moreover, the above mentioned growth regulators overcame the inhibitory effect of JA on the percentages of germination and coleoptile emergence in the same ratio, while GA3 was the most successful hormone on the fresh weight and radicle and coleoptile elongation in comparison with the other growth regulators. Key words: Barley, jasmonic acid, plant growth regulator, seed germination, seedling growth ARPANIN TOHUM ÇİMLENMESİ VE FİDE BÜYÜMESİNİN JASMONİK ASİT TEŞVİKLİ İNHİBİSYONU ÜZERİNE BAZI BİTKİ BÜYÜME DÜZENLEYİCİLERİNİN ETKİLERİ Özet: Arpanın tohum çimlenmesi ve fide büyümesinin jasmonik asit inhibisyonu üzerine gibberellik asit, kinetin, benziladenin, etilen, 24-epibrassinolit ve poliaminlerin (spermin, spermidin, putressin, kadaverin etkileri araştırılmıştır. Çalışılan bitki büyüme düzenleyicilerinin tümünün tohum çimlenmesi ve fide büyümesi üzerinde jasmonik asitin engelleyici etkisini tersine çevirmede başarılı bir performansa sahip oldukları belirlenmiştir. Dahası, yukarıda sözü edilen büyüme düzenleyicileri çimlenme ve koleoptil çıkış yüzdeleri üzerinde aynı oranda etkili olurken, taze ağırlık ve radikula ve koleoptil uzaması üzerinde diğer büyüme düzenleyicileri ile karşılaştırıldığında en başarılı hormon GA3 olmuştur. Anahtar kelimeler: Arpa, jasmonik asit, bitki büyüme düzenleyicisi, tohum çimlenmesi, fide büyümesi

  10. AMP N1-Oxide, a Unique Compound of Royal Jelly, Induces Neurite Outgrowth from PC12 Vells via Signaling by Protein Kinase A Independent of that by Mitogen-Activated Protein Kinase

    Directory of Open Access Journals (Sweden)

    Noriko Hattori

    2010-01-01

    Full Text Available Earlier we identified adenosine monophosphate (AMP N1-oxide as a unique compound of royal jelly (RJ that induces neurite outgrowth (neuritegenesis from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N1-oxide stimulated the phosphorylation of not only mitogen-activated protein kinase (MAPK but also that of cAMP/calcium-response element-binding protein (CREB in a dose-dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N1-oxide-induced neuritegenesis, whereas that of protein kinase A (PKA by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N1-oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth-promoting activity. KT5720 restored the growth of AMP N1-oxide-treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N1-oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor-mediated PKA signaling, which may be responsible for characteristic actions of RJ.

  11. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Univ. of Southern California, Los Angeles, CA (United States)

    2017-10-20

    Objectives: Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass Brachypodium distachyon also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation. Description: The project is divided in three main parts: 1) Performing time-lapse imaging and growth measurement in B. distachyon and S. bicolor to determine growth rate dynamic during the day/night cycle. Identifying growth-associated genes whose expression patterns follow the observed growth dynamics using deep sequencing technology, 2) identifying regulators of these genes by screening for DNA-binding proteins interacting with the growth-associated gene promoters identified in Aim 1. Screens will be performed using a validated yeast-one hybrid strategy paired with a specifically designed B. distachyon and S. bicolor transcription factor libraries (1000 clones each), and 3) Selecting 50 potential growth regulators from the screen for downstream characterization. The selection will be made by using a sytems biology approach by calculating the connectivity between growth rate, rhythmic gene expression profiles and TF expression profile and determine which TF is likely part of a hub

  12. Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth

    Science.gov (United States)

    Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

    2016-05-01

    The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.The development of novel biomaterials that deliver precise regulatory signals to

  13. Linking gene regulation to cell behaviors in the posterior growth zone of sequentially segmenting arthropods.

    Science.gov (United States)

    Williams, Terri A; Nagy, Lisa M

    2017-05-01

    Virtually all arthropods all arthropods add their body segments sequentially, one by one in an anterior to posterior progression. That process requires not only segment specification but typically growth and elongation. Here we review the functions of some of the key genes that regulate segmentation: Wnt, caudal, Notch pathway, and pair-rule genes, and discuss what can be inferred about their evolution. We focus on how these regulatory factors are integrated with growth and elongation and discuss the importance and challenges of baseline measures of growth and elongation. We emphasize a perspective that integrates the genetic regulation of segment patterning with the cellular mechanisms of growth and elongation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth.

    Science.gov (United States)

    Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

    2016-05-21

    The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ∼1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.

  15. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

    Science.gov (United States)

    Weisman, Ronit

    2016-10-01

    All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

  16. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury.

    Science.gov (United States)

    Bucan, Vesna; Vaslaitis, Desiree; Peck, Claas-Tido; Strauß, Sarah; Vogt, Peter M; Radtke, Christine

    2018-06-21

    Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.

  17. Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

    Science.gov (United States)

    Ververis, J; Ku, L; Delafontaine, P

    1994-02-01

    Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

  18. A multilevel latent growth modelling of the longitudinal changes in motivation regulations in physical education.

    Science.gov (United States)

    Jaakkola, Timo; Wang, John; Yli-Piipari, Sami; Liukkonen, Jarmo

    2015-03-01

    The purpose of this study was to examine individual- and classroom-level differences in the longitudinal change in motivational regulations during physical education students' transition from elementary (Grade 6) across middle school (Grades 7 to 9). A sample of 757 Finnish adolescents (M = 12.71, SD = 0.23) participated in this study. Participants of the study responded to questionnaires collected six times. A multilevel latent growth modelling approach was used to analyze the data. Results showed that motivational regulations in physical education developed at different rates during middle school. More specifically, students': (a) identified regulation increased across Grades 6 to 9; (b) amotivation increased during middle school transition from Grade 6 to 7; and (c) introjected regulation declined from Grade 8 to 9. Other motivational regulations remained stable across time. The changes in amotivation and introjected regulation were largely due to individual factors, whereas the changes in identified regulation were due to environmental factors. Key pointsStudents' identified regulation increased across Grades 6 to 9.Students' amotivation increased across middle school transition from Grade 6 to 7.Students' introjected regulation declined from Grade 8 to 9.Other motivational regulations remained stable across time.

  19. Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1.

    Science.gov (United States)

    Li, Wen; Tam, Ka Ming Vincent; Chan, Wai Wan Ray; Koon, Alex Chun; Ngo, Jacky Chi Ki; Chan, Ho Yin Edwin; Lau, Kwok-Fai

    2018-04-03

    Neurite outgrowth is a crucial process in developing neurons for neural network formation. Understanding the regulatory mechanisms of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration after nerve injury and in neurodegenerative disorders. FE65 is a brain-enriched adaptor that stimulates Rac1-mediated neurite elongation. However, the precise mechanism by which FE65 promotes the process remains elusive. Here, we show that ELMO1, a subunit of ELMO1-DOCK180 bipartite Rac1 GEF, interacts with the FE65 N-terminal region. Overexpression of FE65 and/or ELMO1 enhances whereas knockdown of FE65 or ELMO1 inhibits neurite outgrowth and Rac1 activation. The effect of FE65 alone or together with ELMO1 is attenuated by an FE65 double mutation that disrupts FE65-ELMO1 interaction. Notably, FE65 is found to activate ELMO1 by diminishing ELMO1 intramolecular autoinhibitory interaction and to promote the targeting of ELMO1 to the plasma membrane where Rac1 is activated. We also show that FE65, ELMO1 and DOCK180 form a tripartite complex. Knockdown of DOCK180 reduces the stimulatory effect of FE65-ELMO1 on Rac1 activation and neurite outgrowth. Thus, we identify a novel mechanism that FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating of ELMO1. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    Science.gov (United States)

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Scripps Research Inst., La Jolla, CA (United States); Hazen, Samuel [Scripps Research Inst., San Diego, CA (United States); Mullet, John [Texas A & M Univ., College Station, TX (United States)

    2017-11-22

    Critical to the development of renewable energy sources from biofuels is the improvement of biomass from energy feedstocks, such as sorghum and maize. The specific goals of this project include 1) characterize the growth and gene expression patterns under diurnal and circadian conditions, 2) select transcription factors associated with growth and build a cis-regulatory network in yeast, and 3) perturb these transcription factors in planta using transgenic Brachypodium and sorghum, and characterize the phenotypic outcomes as they relate to biomass accumulation. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield.

  2. Interleukin 1 is an autocrine regulator of human endothelial cell growth

    International Nuclear Information System (INIS)

    Cozzolino, F.; Torcia, M.; Aldinucci, D.; Ziche, M.; Bani, D.; Almerigogna, F.; Stern, D.M.

    1990-01-01

    Proliferation of endothelial cells is regulated through the autocrine production of growth factors and the expression of cognate surface receptors. In this study, the authors demonstrate that interleukin 1 (IL-1) is an inhibitor of endothelial growth in vitro and in vivo. IL-1 arrested growing, cultured endothelial cells in G 1 phase; inhibition of proliferation was dose dependent and occurred in parallel with occupancy of endothelial surface IL-1 receptors. In an angiogenesis model, IL-1 could inhibit fibroblast growth factor-induced vessel formation. The autocrine nature of the IL-1 effect on endothelial proliferation was demonstrated by the observation that occupancy of cell-surface receptors by endogenous IL-1 depressed cell growth. The potential significance of this finding was emphasized by the detection of IL-1 in the native endothelium of human umbilical veins. A mechanism by which IL-1 may exert its inhibitory effect on endothelial cell growth was suggested by studies showing that IL-1 decreased the expression of high-affinity fibroblast growth factor binding sites on endothelium. These results point to a potentially important role of IL-1 in regulating blood vessel growth the suggest that autocrine production of inhibitory factors may be a mechanism controlling proliferation of normal cells

  3. Isolation and biological activity of a new plant growth regulator of Vicia faba L

    International Nuclear Information System (INIS)

    Sembdner, G.; Dathe, W.; Bergner, C.; Roensch, H.

    1983-01-01

    Jasmonic acid was identified as a plant growth inhibitor of the pericarp of Vicia faba by means of gas-liquid chromatography, high resolution mass spectrometry as well as 1 H and 13 C NMR. The highest level of jasmonic acid was reached during intensive pericarp growth. Jasmonic acid is a plant growth inhibitor possessing a relative activity in the wheat seedling bioassay of 1-2.5 % compared to ABA (=100%). Contrary to ABA, jasmonic acid does not cause retardation of leaf emergence. In the dwarf rice gibberellin bioassay relative low concentrations of jasmonic acid inhibit both autonomous and GA 3 -stimulated growth. Jasmonic acid does not influence seed germination of Amaranthus caudatus. The possible physiological role of jasmonic acid in the Vicia pericarp and the distribution in plants of this new plant growth regulator type are discussed. (author)

  4. Isolation and biological activity of a new plant growth regulator of Vicia faba L

    Energy Technology Data Exchange (ETDEWEB)

    Sembdner, G.; Dathe, W.; Bergner, C.; Roensch, H. (Akademie der Wissenschaften der DDR, Halle/Saale. Inst. fuer Biochemie der Pflanzen)

    1983-01-01

    Jasmonic acid was identified as a plant growth inhibitor of the pericarp of Vicia faba by means of gas-liquid chromatography, high resolution mass spectrometry as well as /sup 1/H and /sup 13/C NMR. The highest level of jasmonic acid was reached during intensive pericarp growth. Jasmonic acid is a plant growth inhibitor possessing a relative activity in the wheat seedling bioassay of 1-2.5 % compared to ABA (=100%). Contrary to ABA, jasmonic acid does not cause retardation of leaf emergence. In the dwarf rice gibberellin bioassay relative low concentrations of jasmonic acid inhibit both autonomous and GA/sub 3/-stimulated growth. Jasmonic acid does not influence seed germination of Amaranthus caudatus. The possible physiological role of jasmonic acid in the Vicia pericarp and the distribution in plants of this new plant growth regulator type are discussed.

  5. Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

    Science.gov (United States)

    Low, Malcolm J.; Otero-Corchon, Veronica; Parlow, Albert F.; Ramirez, Jose L.; Kumar, Ujendra; Patel, Yogesh C.; Rubinstein, Marcelo

    2001-01-01

    Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth. PMID:11413165

  6. Daily changes in temperature, not the circadian clock, regulate growth rate in Brachypodium distachyon.

    Directory of Open Access Journals (Sweden)

    Dominick A Matos

    Full Text Available Plant growth is commonly regulated by external cues such as light, temperature, water availability, and internal cues generated by the circadian clock. Changes in the rate of growth within the course of a day have been observed in the leaves, stems, and roots of numerous species. However, the relative impact of the circadian clock on the growth of grasses has not been thoroughly characterized. We examined the influence of diurnal temperature and light changes, and that of the circadian clock on leaf length growth patterns in Brachypodium distachyon using high-resolution time-lapse imaging. Pronounced changes in growth rate were observed under combined photocyles and thermocycles or with thermocycles alone. A considerably more rapid growth rate was observed at 28°C than 12°C, irrespective of the presence or absence of light. In spite of clear circadian clock regulated gene expression, plants exhibited no change in growth rate under conditions of constant light and temperature, and little or no effect under photocycles alone. Therefore, temperature appears to be the primary cue influencing observed oscillations in growth rate and not the circadian clock or photoreceptor activity. Furthermore, the size of the leaf meristem and final cell length did not change in response to changes in temperature. Therefore, the nearly five-fold difference in growth rate observed across thermocycles can be attributed to proportionate changes in the rate of cell division and expansion. A better understanding of the growth cues in B. distachyon will further our ability to model metabolism and biomass accumulation in grasses.

  7. Methodology for evaluating the insect growth regulator (IGR) methoprene incorporated into packaging films

    Science.gov (United States)

    The insect growth regulator methoprene has been impregnated onto various packaging materials to control stored product insects, and is labeled for use in this manner in the United States. Different methodologies were utilized to evaluate efficacy towards Tribolium castaneum (Herbst), the red flour b...

  8. A progesterone-brown fat axis is involved in regulating fetal growth.

    NARCIS (Netherlands)

    McIlvride, Saraid; Mushtaq, Aleena; Papacleovoulou, Georgia; Hurling, Chloe; Steel, Jennifer; Jansen, Eugène; Abu-Hayyeh, Shadi; Williamson, Catherine

    2017-01-01

    Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT

  9. delta-EF1 is a negative regulator of Ihh in the developing growth plate.

    Science.gov (United States)

    Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko

    2009-11-30

    Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

  10. Cytokinins as key regulators in plant–microbe–insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    1. Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. 2. Plants are known to rapidly respond to pathogen and herbivore

  11. Effect of gamma radiation and some growth regulators on ripening and senescence in mango fruits

    International Nuclear Information System (INIS)

    EL-Kady, S.M.A.

    1982-01-01

    The present investigation was undertaken during the seasons of 1979 and 1980 to study the effect of gamma irradiation, some growth regulators, benlate and 'vaporgard' on ripening and senescence of 'Hindi Be - Sinnara' mango fruits during storage under room conditions and also to determine the optimum treatment for maximum extension in shelf - life

  12. The effect of plant growth regulators on optimization of tissue culture ...

    African Journals Online (AJOL)

    Mature seeds of four upland rice cultivars namely Kusan, Lamsan, Selasi and Siam were assessed for callus induction and plant regeneration on different concentrations and combinations of plant growth regulators, incorporated into MS (Murashige and Skoog) basal medium. Callus induction frequency was significantly ...

  13. The effect of plant growth regulators on callus initiation in wormwood ...

    African Journals Online (AJOL)

    Studies were carried out in the Biotechnology laboratory of Plant Science Department of Ahmadu Bello University Zaria, Nigeria to study the effect of some plant growth regulators on the in vitro initiation of callus using the leaves of Chiyong variety of Artemisia annua. The explants were sterilized and incubated on Murashige ...

  14. The effect of plant growth regulators and their interaction with electric current on winter wheat development

    Czech Academy of Sciences Publication Activity Database

    Biesaga-Koscielniak, J.; Koscielniak, J.; Filek, M.; Marcinska, I.; Krekule, Jan; Macháčková, Ivana; Kubon, M.

    2010-01-01

    Roč. 32, č. 5 (2010), s. 987-995 ISSN 0137-5881 Institutional research plan: CEZ:AV0Z50380511 Keywords : In vitro culture * Plant growth regulators * Electric current Subject RIV: EF - Botanics Impact factor: 1.344, year: 2010

  15. Genetic activity of plant growth regulators, cartolin and benzilandenin, under ionizing radiation

    International Nuclear Information System (INIS)

    Vilenskij, E.P.

    1987-01-01

    Protective effects of a new cytokinin-type growth regulator cartolin (CRT) are established on a genetic test system of waxy-changes in pollen barley grains under acute irradiation of growing plants. It is shown that the CRT effect is similar to that of synthetic cytokinin benziladenin

  16. Neurite outgrowth stimulatory effects of myco synthesized AuNPs from Hericium erinaceus (Bull.: Fr.) Pers. on pheochromocytoma (PC-12) cells.

    Science.gov (United States)

    Raman, Jegadeesh; Lakshmanan, Hariprasath; John, Priscilla A; Zhijian, Chan; Periasamy, Vengadesh; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Hericium erinaceus has been reported to have a wide range of medicinal properties such as stimulation of neurite outgrowth, promotion of functional recovery of axonotmetic peroneal nerve injury, antioxidant, antihypertensive, and antidiabetic properties. In recent years, the green synthesis of gold nanoparticles (AuNPs) has attracted intense interest due to the potential use in biomedical applications. The aim of this study was to investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite outgrowth of rat pheochromocytoma (PC-12) cells. The formation of AuNPs was characterized by UV-visible spectrum, energy dispersive X-ray (EDX), field-emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), particle size distribution, and Fourier transform-infrared spectroscopy (FTIR). Furthermore, the neurite extension study of synthesized AuNPs was evaluated by in vitro assay. The AuNPs exhibited maximum absorbance between 510 and 600 nm in UV-visible spectrum. FESEM and TEM images showed the existence of nanoparticles with sizes of 20-40 nm. FTIR measurements were carried out to identify the possible biomolecules responsible for capping and efficient stabilization of the nanoparticles. The purity and the crystalline properties were confirmed by EDX diffraction analysis, which showed strong signals with energy peaks in the range of 2-2.4 keV, indicating the existence of gold atoms. The synthesized AuNPs showed significant neurite extension on PC-12 cells. Nerve growth factor 50 ng/mL was used as a positive control. Treatment with different concentrations (nanograms) of AuNPs resulted in neuronal differentiation and neuronal elongation. AuNPs induced maximum neurite outgrowth of 13% at 600 ng/mL concentration. In this study, the AuNPs synthesis was achieved by a simple, low-cost, and rapid bioreduction approach. AuNPs were shown to have potential neuronal differentiation and stimulated neurite outgrowth. The water

  17. Growth-Rate Dependent Regulation of tRNA Level and Charging in Bacillus licheniformis.

    Science.gov (United States)

    Ferro, Iolanda; Liebeton, Klaus; Ignatova, Zoya

    2017-10-13

    Cellular growth crucially depends on protein synthesis and the abundance of translational components. Among them, aminoacyl-tRNAs play a central role in biosynthesis and shape the kinetics of mRNA translation, thus influencing protein production. Here, we used microarray-based approaches to determine the charging levels and tRNA abundance of Bacillus licheniformis. We observed an interesting cross-talk among tRNA expression, charging pattern, and growth rate. For a large subset of tRNAs, we found a co-regulated and augmented expression at high growth rate. Their tRNA aminoacylation level is kept relatively constant through riboswitch-regulated expression of the cognate aminoacyl-tRNA-synthetase (AARS). We show that AARSs with putative riboswitch-controlled expression are those charging tRNAs with amino acids which disfavor cell growth when individually added to the nutrient medium. Our results suggest that the riboswitch-regulated AARS expression in B. licheniformis is a powerful mechanism not only to maintain a constant ratio of aminoacyl-tRNA independent of the growth rate but concomitantly to control the intracellular level of free amino acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

    International Nuclear Information System (INIS)

    DiCicco-Bloom, E.; Black, I.B.

    1988-01-01

    While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [ 3 H]thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of [ 3 H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain

  19. Synthesis Of 2- (1- Naphthyl) Ethanoic Acid ( Plant Growth Regulator ) From Coal Tar And Its Application

    International Nuclear Information System (INIS)

    Khin Mooh Theint; Tin Myint Htwe

    2011-12-01

    Plant growth regulators, which are commonly called as plant hormones, naturally produced non-nutrient chemical compounds involved in growth and development. Among the various kinds of plant growth regulators, 2- (1- Naphthyl ) ethanoic acid especially encourages the root development of the plant. In this work, NAA was successfuly synthesized from naphthalene which was extracted from coal tar. The purity of naphthalene, -Chloromethyl naphthalene, -Naphthyl acetonitrile, - Naphthyl acetic acid or 2 - ( 1-Naphthyl ) ethanoic acid were also confirmed by Thin Layer Chromatography, and by spectroscopy methods. The yield percent of NAA based on naphthalene was found to be 2.1%. The yield percent of naphthaleneFrom coal tar is found to be 4.09%. The effect of NAA on root development was also studied in different concentrations of soy bean (Glycine max)and cow pea (Vigna catjang walp).

  20. Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors

    Directory of Open Access Journals (Sweden)

    Justin D. Schumacher

    2016-01-01

    Full Text Available Fibroblast growth factors (FGFs are a family of growth factors critically involved in developmental, physiological, and pathological processes, including embryogenesis, angiogenesis, wound healing, and endocrine functions. In the liver, several FGFs are produced basally by hepatocytes and hepatic stellate cells (HSCs. Upon insult to the liver, expression of FGFs in HSCs is greatly upregulated, stimulating hepatocyte regeneration and growth. Various FGF isoforms have also been shown to directly induce HSC proliferation and activation thereby enabling autocrine and paracrine regulation of HSC function. Regulation of HSCs by the endocrine FGFs, namely, FGF15/19 and FGF21, has also recently been identified. With the ability to modulate HSC proliferation and transdifferentiation, targeting FGF signaling pathways constitutes a promising new therapeutic strategy to treat hepatic fibrosis.

  1. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

    Science.gov (United States)

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, W E

    2010-05-01

    beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.

  2. Emergence of robust growth laws from optimal regulation of ribosome synthesis.

    Science.gov (United States)

    Scott, Matthew; Klumpp, Stefan; Mateescu, Eduard M; Hwa, Terence

    2014-08-22

    Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large-scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome-wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply-driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  3. Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings

    International Nuclear Information System (INIS)

    Uranga, Carla C.; Beld, Joris; Mrse, Anthony; Córdova-Guerrero, Iván; Burkart, Michael D.; Hernández-Martínez, Rufina

    2016-01-01

    The Botryosphaeriaceae are a family of trunk disease fungi that cause dieback and death of various plant hosts. This work sought to characterize fatty acid derivatives in a highly virulent member of this family, Lasiodiplodia theobromae. Nuclear magnetic resonance and gas chromatography-mass spectrometry of an isolated compound revealed (Z, Z)-9,12-ethyl octadecadienoate, (trivial name ethyl linoleate), as one of the most abundant fatty acid esters produced by L. theobromae. A variety of naturally produced esters of fatty acids were identified in Botryosphaeriaceae. In comparison, the production of fatty acid esters in the soil-borne tomato pathogen Fusarium oxysporum, and the non-phytopathogenic fungus Trichoderma asperellum was found to be limited. Ethyl linoleate, ethyl hexadecanoate (trivial name ethyl palmitate), and ethyl octadecanoate, (trivial name ethyl stearate), significantly inhibited tobacco seed germination and altered seedling leaf growth patterns and morphology at the highest concentration (0.2 mg/mL) tested, while ethyl linoleate and ethyl stearate significantly enhanced growth at low concentrations, with both still inducing growth at 98 ng/mL. This work provides new insights into the role of naturally esterified fatty acids from L. theobromae as plant growth regulators with similar activity to the well-known plant growth regulator gibberellic acid. - Highlights: • Lasiodiplodia theobromae produces a wide variety of fatty acid esters in natural substrates. • Ethyl stearate and ethyl linoleate inhibit tobacco germination at 0.2 mg/mL. • Ethyl stearate and ethyl linoleate induce tobacco germination at 98 ng/mL. • Tobacco growth increase in ethyl stearate and ethyl linoleate parallels gibberellic acid. • A role as plant growth regulators is proposed for fatty acid esters.

  4. Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings

    Energy Technology Data Exchange (ETDEWEB)

    Uranga, Carla C., E-mail: curanga@cicese.edu.mx [Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana 3918, Zona Playitas, 22860 Ensenada, B.C. (Mexico); Beld, Joris, E-mail: joris.beld@drexelmed.edu [University of California, San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0358 (United States); Mrse, Anthony, E-mail: amrse@ucsd.edu [University of California, San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0358 (United States); Córdova-Guerrero, Iván, E-mail: icordova@uabc.edu.mx [Universidad Autónoma de Baja California (UABC), Calzada Universidad 14418 Parque Industrial Internacional Tijuana, Tijuana, B.C. 22390 (Mexico); Burkart, Michael D., E-mail: mburkart@ucsd.edu [University of California, San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Dr., La Jolla, CA 92093-0358 (United States); Hernández-Martínez, Rufina, E-mail: ruhernan@cicese.mx [Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana 3918, Zona Playitas, 22860 Ensenada, B.C. (Mexico)

    2016-04-01

    The Botryosphaeriaceae are a family of trunk disease fungi that cause dieback and death of various plant hosts. This work sought to characterize fatty acid derivatives in a highly virulent member of this family, Lasiodiplodia theobromae. Nuclear magnetic resonance and gas chromatography-mass spectrometry of an isolated compound revealed (Z, Z)-9,12-ethyl octadecadienoate, (trivial name ethyl linoleate), as one of the most abundant fatty acid esters produced by L. theobromae. A variety of naturally produced esters of fatty acids were identified in Botryosphaeriaceae. In comparison, the production of fatty acid esters in the soil-borne tomato pathogen Fusarium oxysporum, and the non-phytopathogenic fungus Trichoderma asperellum was found to be limited. Ethyl linoleate, ethyl hexadecanoate (trivial name ethyl palmitate), and ethyl octadecanoate, (trivial name ethyl stearate), significantly inhibited tobacco seed germination and altered seedling leaf growth patterns and morphology at the highest concentration (0.2 mg/mL) tested, while ethyl linoleate and ethyl stearate significantly enhanced growth at low concentrations, with both still inducing growth at 98 ng/mL. This work provides new insights into the role of naturally esterified fatty acids from L. theobromae as plant growth regulators with similar activity to the well-known plant growth regulator gibberellic acid. - Highlights: • Lasiodiplodia theobromae produces a wide variety of fatty acid esters in natural substrates. • Ethyl stearate and ethyl linoleate inhibit tobacco germination at 0.2 mg/mL. • Ethyl stearate and ethyl linoleate induce tobacco germination at 98 ng/mL. • Tobacco growth increase in ethyl stearate and ethyl linoleate parallels gibberellic acid. • A role as plant growth regulators is proposed for fatty acid esters.

  5. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2017-06-15

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

  6. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    International Nuclear Information System (INIS)

    Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

    2017-01-01

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

  7. Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

    Directory of Open Access Journals (Sweden)

    Carlstrom Lucas P

    2011-11-01

    Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

  8. Stiff mutant genes of Phycomyces target turgor pressure and wall mechanical properties to regulate elongation growth rate

    Directory of Open Access Journals (Sweden)

    Joseph K. E. Ortega

    2012-05-01

    Full Text Available Regulation of cell growth is paramount to all living organisms. In plants, algae and fungi, regulation of expansive growth of cells is required for development and morphogenesis. Also, many sensory responses of stage IVb sporangiophores of Phycomyces blakesleeanus are produced by regulating elongation growth rate (growth responses and differential elongation growth rate (tropic responses. Stiff mutant sporangiophores exhibit diminished tropic responses and are found to be defective in at least four genes; madD, madE, madF and madG. Prior experimental research suggests that the defective genes affect growth regulation, but this was not verified. All the growth of the single-celled stalk of the stage IVb sporangiophore occurs in a short region termed the growth zone. Prior experimental and theoretical research indicates that elongation growth rate of the stage IVb sporangiophore can be regulated by controlling the cell wall mechanical properties within the growth zone and the magnitude of the turgor pressure. A quantitative biophysical model for elongation growth rate is required to elucidate the relationship between wall mechanical properties and turgor pressure during growth regulation. In this study, it is hypothesized that the mechanical properties of the wall within the growth zone of stiff mutant sporangiophores are different compared to wild type. A biophysical equation for elongation growth rate is derived for fungal and plant cells with a growth zone. Two strains of stiff mutants are studied, C149 madD120 (- and C216 geo- (-. Experimental results demonstrate that turgor pressure is larger but irreversible deformation rates of the wall within the growth zone and growth zone length are smaller for stiff mutant sporangiophores compared to wild type. These findings explain the diminished tropic responses of the stiff mutant sporangiophores and suggest that the defective genes affect the amount of wall-building material delivered to the inner

  9. A low-cost microwell device for high-resolution imaging of neurite outgrowth in 3D

    Science.gov (United States)

    Ren, Yuan; Mlodzianoski, Michael J.; Cheun Lee, Aih; Huang, Fang; Suter, Daniel M.

    2018-06-01

    Objective. Current neuronal cell culture is mostly performed on two-dimensional (2D) surfaces, which lack many of the important features of the native environment of neurons, including topographical cues, deformable extracellular matrix, and spatial isotropy or anisotropy in three dimensions. Although three-dimensional (3D) cell culture systems provide a more physiologically relevant environment than 2D systems, their popularity is greatly hampered by the lack of easy-to-make-and-use devices. We aim to develop a widely applicable 3D culture procedure to facilitate the transition of neuronal cultures from 2D to 3D. Approach. We made a simple microwell device for 3D neuronal cell culture that is inexpensive, easy to assemble, and fully compatible with commonly used imaging techniques, including super-resolution microscopy. Main results. We developed a novel gel mixture to support 3D neurite regeneration of Aplysia bag cell neurons, a system that has been extensively used for quantitative analysis of growth cone dynamics in 2D. We found that the morphology and growth pattern of bag cell growth cones in 3D culture closely resemble the ones of growth cones observed in vivo. We demonstrated the capability of our device for high-resolution imaging of cytoskeletal and signaling proteins as well as organelles. Significance. Neuronal cell culture has been a valuable tool for neuroscientists to study the behavior of neurons in a controlled environment. Compared to 2D, neurons cultured in 3D retain the majority of their native characteristics, while offering higher accessibility, control, and repeatability. We expect that our microwell device will facilitate a wider adoption of 3D neuronal cultures to study the mechanisms of neurite regeneration.

  10. Comparison of neurite density measured by MRI and histology after TBI.

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    Shiyang Wang

    Full Text Available Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI with and without MSC treatment.Fifteen male Wistar rats, were treated with saline (n = 6 or MSCs (n = 9 and were sacrificed at 6 weeks after controlled cortical impact (CCI. Healthy non-CCI rats (n = 5, were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients.Neurite densities exhibited a significant correlation (R(2>0.80, p<1E-20 between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC as 0.86. The conventional fractional anisotropy (FA correlated moderately with histological neurite density (R(2 = 0.59, P<1E-5 with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region.The present studies

  11. Effectiveness of growth regulators, based on the heterylcarbon acid, on forcing of Tulips (Tulips HD

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    Derevianko Natalia

    2016-03-01

    Full Text Available The main factor in growing flowers for forcing is their rate of growth, on account of the fact that in short period of time it is necessary to grow quickly a large number of flowers and to cut them simultaneously. The influence of growth regulators (GR based on heterylcarbon acid on the forcing of tulips in greenhouse conditions (winter period was studied. It was determined that the application of GR1 of the basic within tulip’s forcing period reduces in average to 5 days (from all period of forcing. In case of application GR2 the tulip’s forcing period also reduces to 3 days (from all period of forcing compared with a control group of tulips. The ability of the plant growth regulators under research to accelerate growing properties of flowers is associated with the presence of heterylcarbon acid and potassium ions in their structure of substances. These growth regulators relate to non-toxic compounds and possess antioxidant properties.

  12. Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway

    International Nuclear Information System (INIS)

    Alleaume, Celine; Eychene, Alain; Harnois, Thomas; Bourmeyster, Nicolas; Constantin, Bruno; Caigneaux, Evelyne; Muller, Jean-Marc; Philippe, Michel

    2004-01-01

    Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells

  13. Prioritizing plant defence over growth through WRKY regulation facilitates infestation by non-target herbivores

    Science.gov (United States)

    Li, Ran; Zhang, Jin; Li, Jiancai; Zhou, Guoxin; Wang, Qi; Bian, Wenbo; Erb, Matthias; Lou, Yonggen

    2015-01-01

    Plants generally respond to herbivore attack by increasing resistance and decreasing growth. This prioritization is achieved through the regulation of phytohormonal signaling networks. However, it remains unknown how this prioritization affects resistance against non-target herbivores. In this study, we identify WRKY70 as a specific herbivore-induced, mitogen-activated protein kinase-regulated rice transcription factor that physically interacts with W-box motifs and prioritizes defence over growth by positively regulating jasmonic acid (JA) and negatively regulating gibberellin (GA) biosynthesis upon attack by the chewing herbivore Chilo suppressalis. WRKY70-dependent JA biosynthesis is required for proteinase inhibitor activation and resistance against C. suppressalis. In contrast, WRKY70 induction increases plant susceptibility against the rice brown planthopper Nilaparvata lugens. Experiments with GA-deficient rice lines identify WRKY70-dependent GA signaling as the causal factor in N. lugens susceptibility. Our study shows that prioritizing defence over growth leads to a significant resistance trade-off with important implications for the evolution and agricultural exploitation of plant immunity. DOI: http://dx.doi.org/10.7554/eLife.04805.001 PMID:26083713

  14. Grass Carp Follisatin: Molecular Cloning, Functional Characterization, Dopamine D1 Regulation at Pituitary Level, and Implication in Growth Hormone Regulation

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    Roger S. K. Fung

    2017-08-01

    Full Text Available Activin is involved in pituitary hormone regulation and its pituitary actions can be nullified by local production of its binding protein follistatin. In our recent study with grass carp, local release of growth hormone (GH was shown to induce activin expression at pituitary level, which in turn could exert an intrapituitary feedback to inhibit GH synthesis and secretion. To further examine the activin/follistatin system in the carp pituitary, grass carp follistatin was cloned and confirmed to be single-copy gene widely expressed at tissue level. At the pituitary level, follistatin signals could be located in carp somatotrophs, gonadotrophs, and lactotrophs. Functional expression also revealed that carp follistatin was effective in neutralizing activin’s action in stimulating target promoter with activin-responsive elements. In grass carp pituitary cells, follistatin co-treatment was found to revert activin inhibition on GH mRNA expression. Meanwhile, follistatin mRNA levels could be up-regulated by local production of activin but the opposite was true for dopaminergic activation with dopamine (DA or its agonist apomorphine. Since GH stimulation by DA via pituitary D1 receptor is well-documented in fish models, the receptor specificity for follistatin regulation by DA was also investigated. Using a pharmacological approach, the inhibitory effect of DA on follistatin gene expression was confirmed to be mediated by pituitary D1 but not D2 receptor. Furthermore, activation of D1 receptor by the D1-specific agonist SKF77434 was also effective in blocking follistatin mRNA expression induced by activin and GH treatment both in carp pituitary cells as well as in carp somatotrophs enriched by density gradient centrifugation. These results, as a whole, suggest that activin can interact with dopaminergic input from the hypothalamus to regulate follistatin expression in carp pituitary, which may contribute to GH regulation by activin/follistatin system

  15. Zebrafish diras1 Promoted Neurite Outgrowth in Neuro-2a Cells and Maintained Trigeminal Ganglion Neurons In Vivo via Rac1-Dependent Pathway.

    Science.gov (United States)

    Yeh, Chi-Wei; Hsu, Li-Sung

    2016-12-01

    The small GTPase Ras superfamily regulates several neuronal functions including neurite outgrowth and neuron proliferation. In this study, zebrafish diras1a and diras1b were identified and were found to be mainly expressed in the central nervous system and dorsal neuron ganglion. Overexpression of green fluorescent protein (GFP)-diras1a or GFP-diras1b triggered neurite outgrowth of Neuro-2a cells. The wild types, but not the C terminus truncated forms, of diras1a and diras1b elevated the protein level of Ras-related C3 botulinum toxin substrate 1 (Rac1) and downregulated Ras homologous member A (RhoA) expression. Glutathione S-transferase (GST) pull-down assay also revealed that diras1a and diras1b enhanced Rac1 activity. Interfering with Rac1, Pak1, or cyclin-dependent kinase 5 (CDK5) activity or with the Arp2/3 inhibitor prevented diras1a and diras1b from mediating the neurite outgrowth effects. In the zebrafish model, knockdown of diras1a and/or diras1b by morpholino antisense oligonucleotides not only reduced axon guidance but also caused the loss of trigeminal ganglion without affecting the precursor markers, such as ngn1 and neuroD. Co-injection with messenger RNA (mRNA) derived from mouse diras1 or constitutively active human Rac1 restored the population of trigeminal ganglion. In conclusion, we provided preliminary evidence that diras1 is involved in neurite outgrowth and maintains the number of trigeminal ganglions through the Rac1-dependent pathway.

  16. Vitamin B12–dependent taurine synthesis regulates growth and bone mass

    Science.gov (United States)

    Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

    2014-01-01

    Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

  17. Growth regulating properties of isoprene and isoprenoid-based essential oils.

    Science.gov (United States)

    Jones, Andrew Maxwell P; Shukla, Mukund R; Sherif, Sherif M; Brown, Paula B; Saxena, Praveen K

    2016-01-01

    Essential oils have growth regulating properties comparable to the well-documented methyl jasmonate and may be involved in localized and/or airborne plant communication. Aromatic plants employ large amounts of resources to produce essential oils. Some essential oils are known to contain compounds with plant growth regulating activities. However, the potential capacity of essential oils as airborne molecules able to modulate plant growth/development has remained uninvestigated. Here, we demonstrate that essential oils from eight taxonomically diverse plants applied in their airborne state inhibited auxin-induced elongation of Pisum sativum hypocotyls and Avena sativa coleoptiles. This response was also observed using five monoterpenes commonly found in essential oils as well as isoprene, the basic building block of terpenes. Upon transfer to ambient conditions, A. sativa coleoptiles resumed elongation, demonstrating an antagonistic relationship rather than toxicity. Inclusion of essential oils, monoterpenes, or isoprene into the headspace of culture vessels induced abnormal cellular growth along hypocotyls of Arabidopsis thaliana. These responses were also elicited by methyl jasmonate (MeJA); however, where methyl jasmonate inhibited root growth essential oils did not. Gene expression studies in A. thaliana also demonstrated differences between the MeJA and isoprenoid responses. This series of experiments clearly demonstrate that essential oils and their isoprenoid components interact with endogenous plant growth regulators when applied directly or as volatile components in the headspace. The similarities between isoprenoid and MeJA responses suggest that they may act in plant defence signalling. While further studies are needed to determine the ecological and evolutionary significance, the results of this study and the specialized anatomy associated with aromatic plants suggest that essential oils may act as airborne signalling molecules.

  18. E2F1 regulates cellular growth by mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Sebastian Real

    2011-01-01

    Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

  19. Sigma-1 receptor enhances neurite elongation of cerebellar granule neurons via TrkB signaling.

    Science.gov (United States)

    Kimura, Yuriko; Fujita, Yuki; Shibata, Kumi; Mori, Megumi; Yamashita, Toshihide

    2013-01-01

    Sigma-1 receptor (Sig-1R) is an integral membrane protein predominantly expressed in the endoplasmic reticulum. Sig-1R demonstrates a high affinity to various synthetic compounds including well-known psychotherapeutic drugs in the central nervous system (CNS). For that, it is considered as an alternative target for psychotherapeutic drugs. On the cellular level, when Sig-1R is activated, it is known to play a role in neuroprotection and neurite elongation. These effects are suggested to be mediated by its ligand-operated molecular chaperone activity, and/or upregulation of various Ca(2+) signaling. In addition, recent studies show that Sig-1R activation induces neurite outgrowth via neurotrophin signaling. Here, we tested the hypothesis that Sig-1R activation promotes neurite elongation through activation of tropomyosin receptor kinase (Trk), a family of neurotrophin receptors. We found that 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084), a selective Sig-1R agonist, significantly promoted neurite outgrowth, and K252a, a Trk inhibitor, attenuated Sig-1R-mediated neurite elongation in cerebellar granule neurons (CGNs). Moreover, we revealed that Sig-1R interacts with TrkB, and PRE-084 treatment enhances phosphorylation of Y515, but not Y706. Thus, our results indicate that Sig-1R activation promotes neurite outgrowth in CGNs through Y515 phosphorylation of TrkB.

  20. Chimeric ZHHH neuroglobin acts as a cell membrane-penetrating inducer of neurite outgrowth.

    Science.gov (United States)

    Takahashi, Nozomu; Onozuka, Wataru; Watanabe, Seiji; Wakasugi, Keisuke

    2017-09-01

    Neuroglobin (Ngb) is a heme protein expressed in the vertebrate brain. We previously engineered a chimeric Ngb protein, in which module M1 of human Ngb is replaced by that of zebrafish Ngb, and showed that the chimeric ZHHH Ngb has a cell membrane-penetrating activity similar to that of zebrafish Ngb and also rescues cells from death caused by hypoxia/reoxygenation as does human Ngb. Recently, it was reported that overexpression of mammalian Ngb in neuronal cells induces neurite outgrowth. In this study, we performed neurite outgrowth assays of chimeric Ngb using rat pheochromocytoma PC12 cells. Addition of chimeric Ngb, but not human or zebrafish Ngb, exogenously to the cell medium induces neurite outgrowth. On the other hand, the K7A/K9Q chimeric Ngb double mutant, which cannot translocate into cells, did not induce neurite outgrowth, suggesting that the cell membrane-penetrating activity of the chimeric Ngb is crucial for its neurite outgrowth-promoting activity. We also prepared several site-directed chimeric Ngb mutants and demonstrated that residues crucial for neurite outgrowth-inducing activity of the chimeric Ngb are not exactly the same as those for its neuroprotective activity.

  1. Overview of OVATE FAMILY PROTEINS, a novel class of plant-specific growth regulators

    Directory of Open Access Journals (Sweden)

    Shucai eWang

    2016-03-01

    Full Text Available OVATE FAMILY PROTEINS (OFPs are a class of proteins with a conserved OVATE domain. OVATE protein was first identified in tomato as a key regulator of fruit shape. OFPs are plant-specific proteins that are widely distributed in the plant kingdom including mosses and lycophytes. Transcriptional activity analysis of Arabidopsis OFPs (AtOFPs in protoplasts suggests that they act as transcription repressors. Functional characterization of OFPs from different plant species including Arabidopsis, rice, tomato, pepper and banana suggests that OFPs regulate multiple aspects of plant growth and development, which is likely achieved by interacting with different types of transcription factors including the KNOX and BELL classes, and/or directly regulating the expression of target genes such as Gibberellin 20 oxidase (GA20ox. Here, we examine how OVATE was originally identified, summarize recent progress in elucidation of the roles of OFPs in regulating plant growth and development, and describe possible mechanisms underpinning this regulation. Finally, we review potential new research directions that could shed additional light on the functional biology of OFPs in plants.

  2. Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance.

    Science.gov (United States)

    Turney, Stephen G; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B; Goeckeler, Zoe M; Rioux, Robert M; Whitesides, George M; Bridgman, Paul C

    2016-02-01

    Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. © 2016 Turney et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Synthesis and evaluation of the plant growth regulator property of indolic compounds derived from safrole

    International Nuclear Information System (INIS)

    Marchi, Irineu; Rebelo, Ricardo Andrade; Rosa, Flavia A. Fernandes da; Maiochi, Riceli A.

    2007-01-01

    The present work describes the use of piperonal, a derivative of the secondary metabolite safrole, for the synthesis of new 5,6-methylenedioxy substituted indole carboxylic acids structurally related to the indol-3-yl-acetic acid (AIA, I). The route comprises six steps beginning with piperonal with an overall yield of 19%. Compound IX was tested towards its plant growth regulator properties in bioassays specific for auxine activity. The in vitro assays were performed in a germination chamber and were of two types: root growth in germinated seeds of Lactuca sativa, Cucumbis sativus and Raphanus sativus and peciole biotest using Phaseolus vulgaris. (author)

  4. Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

    OpenAIRE

    Layton, Tracy; Stalens, Cristel; Gunderson, Felizza; Goodison, Steve; Silletti, Steve

    2009-01-01

    We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC cells in vitro and in situ, and stable reexpression of syk in endogenously syk-negative Panc1 (Panc1/syk) cells retarded their growth in vitro and in vivo and reduced anchorage-independent growth in vitro. Panc1/syk cells exhibited a more differentiated morphology and down-regulated cyclin D1, ak...

  5. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

    OpenAIRE

    Haricharan, Svasti; Brown, Powel

    2015-01-01

    This study fundamentally alters our understanding of how TLR4 drives breast cancer. Although TLR4 was previously considered a tumor promoter, we demonstrate a complex, TP53-dependent role for TLR4 in regulating tumor growth. TP53 is a tumor suppressor commonly inactivated across cancer types. In TP53 wild-type cancer cells, TLR4 activation causes secretion of IFN-γ into the microenvironment, resulting in induction of p21 and inhibition of cell growth. Conversely, TLR4 activation in TP53 mutan...

  6. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

    Science.gov (United States)

    Haricharan, Svasti; Brown, Powel

    2015-06-23

    Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

  7. Ubiquitination of MBNL1 Is Required for Its Cytoplasmic Localization and Function in Promoting Neurite Outgrowth

    Directory of Open Access Journals (Sweden)

    Pei-Ying Wang

    2018-02-01

    Full Text Available The Muscleblind-like protein family (MBNL plays an important role in regulating the transition between differentiation and pluripotency and in the pathogenesis of myotonic dystrophy type 1 (DM1, a CTG expansion disorder. How different MBNL isoforms contribute to the differentiation and are affected in DM1 has not been investigated. Here, we show that the MBNL1 cytoplasmic, but not nuclear, isoform promotes neurite morphogenesis and reverses the morphological defects caused by expanded CUG RNA. Cytoplasmic MBNL1 is polyubiquitinated by lysine 63 (K63. Reduced cytoplasmic MBNL1 in the DM1 mouse brain is consistent with the reduced extent of K63 ubiquitination. Expanded CUG RNA induced the deubiqutination of cytoplasmic MBNL1, which resulted in nuclear translocation and morphological impairment that could be ameliorated by inhibiting K63-linked polyubiquitin chain degradation. Our results suggest that K63-linked ubiquitination of MBNL1 is required for its cytoplasmic localization and that deubiquitination of cytoplasmic MBNL1 is pathogenic in the DM1 brain.

  8. Effects of light and growth regulators on adventitious bud formation in horseradish (Armoracia rusticana).

    Science.gov (United States)

    Kamada, H; Tachikawa, Y; Saitou, T; Harada, H

    1995-07-01

    To clarify that the presence of Ri T-DNA genes are not prerequisite for the light-induced bud formation in horseradish (Armoracia rusticana) hairy roots, leaf and root segments of nontransformed horseradish plants were used as explants. Bud formation from nontransformed tissues was observed in hormone-free medium under 16 h daylight conditions, but not under continuous darkness. To investigate the effects of growth regulators on bud formation, leaf and root explants were treated with auxin (1-naphthaleneacetic acid; NAA) and / or cytokinin (6-benzyl-aminopurine; BA). The most effective treatment in the dark to stimulate bud formation was BA at 1 mg·1(-1). These results show that adventitious bud formation in horseradish can be induced by light and growth regulators, and especially cytokinin, may be involved in bud formation, irrespective of whether the tissues were transformed with Ri T-DNA.

  9. Exogenously applied plant growth regulators enhance the morpho-physiological growth and yield of rice under high temperature

    Directory of Open Access Journals (Sweden)

    Shah Fahad

    2016-08-01

    Full Text Available A two-year experiment was conducted to ascertain the effects of exogenously applied plant growth regulators (PGR on rice growth and yield attributes under high day (HDT and high night temperature (HNT. Two rice cultivars (IR-64 and Huanghuazhan were subjected to temperature treatments in controlled growth chambers and four different combinations of ascorbic acid (Vc, alpha-tocopherol (Ve, brassinosteroids (Br, methyl jasmonates (MeJA and triazoles (Tr were applied. High temperature severely affected rice morphology, and also reduced leaf area, above- and below-ground biomass, photosynthesis, and water use efficiency, while increased the leaf water potential of both rice cultivars. Grain yield and its related attributes except number of panicles, were reduced under high temperature. The HDT posed more negative effects on rice physiological attributes, while HNT was more detrimental for grain formation and yield. The Huanghuazhan performed better than IR-64 under high temperature stress with better growth and higher grain yield. Exogenous application of PGRs was helpful in alleviating the adverse effects of high temperature. Among PGR combinations, the Vc+Ve+MejA+Br was the most effective treatment for both cultivars under high temperature stress. The highest grain production by Vc+Ve+MejA+Br treated plants was due to enhanced photosynthesis, spikelet fertility and grain filling, which compensated the adversities of high temperature stress. Taken together, these results will be of worth for further understanding the adaptation and survival mechanisms of rice to high temperature and will assist in developing heat-resistant rice germplasm in future.

  10. Regulation of myostatin expression is associated with growth and muscle development in commercial broiler and DMC muscle

    NARCIS (Netherlands)

    Dou, Tengfei; Li, Zhengtian; Wang, Kun; Liu, Lixian; Rong, Hua; Xu, Zhiqiang; Huang, Ying; Gu, Dahai; Chen, Xiaobo; Hu, Wenyuan; Zhang, Jiarong; Zhao, Sumei; Jois, Markandeya; Li, Qihua; Ge, Changrong; Pas, te Marinus F.W.; Jia, Junjing

    2018-01-01

    Myostatin is a negative regulator of skeletal muscle growth. Muscle tissue is the largest tissue in the body and influences body growth. Commercial Avian broiler chickens are selected for high growth rate and muscularity. Daweishan mini chickens are a slow growing small-sized chicken breed. We

  11. The Use of Plant Growth Regulators to Improve the Traffic Tolerance and Repair of Overseeded Bermudagrass

    OpenAIRE

    Marshall, Christopher Scott

    2007-01-01

    An active football season during the fall acclimation period tests the traffic tolerance of bermudagrass. Exogenous applications of synthetic cytokinins or cytokinin-enhancing plant growth regulators (PGRs), such as trinexapac-ethyl, may improve the traffic tolerance of "Patriot" and "Tifsport" hybrid berudagrasses (Cynodon dactylon var. dactylon x Cynodon transvaalensis). This study was designed to mimic the agronomic practices and traffic stresses experienced at Virginia Tech's Worsham Fiel...

  12. Flavonols Mediate Root Phototropism and Growth through Regulation of Proliferation-to-Differentiation Transition

    OpenAIRE

    Silva, Javier; Moreno Risueño, Miguel Ángel; Manzano, Concepción; Téllez Robledo, Bárbara; Navarro Neila, Sara; Carrasco Loba, Víctor; Pollmann, Stephan; Gallego, Javier; Pozo Benito, Juan Carlos del

    2016-01-01

    Roots normally grow in darkness, but they may be exposed to light. After perceiving light, roots bend to escape from light (root light avoidance) and reduce their growth. How root light avoidance responses are regulated is not well understood. Here, we show that illumination induces the accumulation of flavonols in Arabidopsis thaliana roots. During root illumination, flavonols rapidly accumulate at the side closer to light in the transition zone. This accumulation promotes asymmetrical cell ...

  13. Effects of reduced-risk pesticides and plant growth regulators on rove beetle (Coleoptera: Staphylinidae) adults.

    Science.gov (United States)

    Echegaray, Erik R; Cloyd, Raymond A

    2012-12-01

    In many regions, pest management of greenhouse crops relies on the use of biological control agents; however, pesticides are also widely used, especially when dealing with multiple arthropod pests and attempting to maintain high esthetic standards. As such, there is interest in using biological control agents in conjunction with chemical control. However, the prospects of combining natural enemies and pesticides are not well known in many systems. The rove beetle, Atheta coriaria (Kraatz), is a biological control agent mainly used against fungus gnats (Bradysia spp.). This study evaluated the effects of reduced-risk pesticides and plant growth regulators on A. coriaria adult survival, development, and prey consumption under laboratory conditions. Rove beetle survival was consistently higher when adults were released 24 h after rather than before applying pesticides. The pesticides acetamiprid, lambda-cyhalothrin, and cyfluthrin were harmful to rove beetle adults, whereas Beauveria bassiana (Balsamo) Vuillemin, azadirachtin, and organic oils (cinnamon oils, rosemary oil, thyme oil, and clove oil) were nontoxic to A. coriaria adults. Similarly, the plant growth regulators acymidol, paclobutrazol, and uniconazole were not harmful to rove beetle adults. In addition, B. bassiana, azadirachtin, kinoprene, organic oils, and the plant growth regulators did not negatively affect A. coriaria development. However, B. bassiana did negatively affect adult prey consumption. This study demonstrated that A. coriaria may not be used when applying the pesticides, acetamiprid, lambda-cyhalothrin, and cyfluthrin, whereas organic oils, B. bassiana, azadirachtin, and the plant growth regulators evaluated may be used in conjunction with A. coriaria adults. As such, these compounds may be used in combination with A. coriaria in greenhouse production systems.

  14. The effect of growth regulators on the uptake and distribution of calcium in Golden Delicious apples

    International Nuclear Information System (INIS)

    Steenkamp, J.; De Villiers, O.T.

    1979-01-01

    45 Ca, applied to the roots of Golden Delicious apple seedlings, was readily absorbed and transported to the leaves. Application of NAAm to the leaves of seedlings significantly increased the uptake of 45 Ca, whereas the growth regulators GA 3 , kinetin, SADH, CEPA and 2,4,5-TP had no such effect. Application of NAAm to intact fruits and fruit discs also significantly increased the uptake of 45 Ca [af

  15. Improvement of Salt Tolerance in Trigonella foenum-graecum L. var. PEB by Plant Growth Regulators

    Directory of Open Access Journals (Sweden)

    Anjali Ratnakar

    2014-05-01

    Full Text Available The crop yield is reduced under saline conditions and this hampers agricultural productivity. The incorporation of plant growth regulators (PGRs during presoaking treatments in many crops has improved seed performance under saline conditions. In order to study the ameliorative effect of plant growth regulators, experiments were conducted to study the variation in organic constituents in the leaves of Trigonella foenum-graecum L. var.PEB, where the seeds were primed with different plant growth regulators and grown under NaCl salinity. After a pre-soaking treatment of six hours in 20 mg L-1 solutions of gibberllic acid (GA3, 6-furfuryladenine (Kinetin and benzyl adenine (BA, the seeds were allowed to germinate and grow for forty-five days under saline conditions. On the analysis of mature leaves, it was observed that chlorophyll a and b, total chlorophyll and protein showed an increase in PGR-treated plants compared to the untreated set. The accumulation of the stress metabolite such as proline and sugars, which increase under saline conditions, showed a significant decrease in the plants pretreated with PGRs.

  16. Role of plant growth regulators on oil yield and biodiesel production of linseed (linum usitatissimum l)

    International Nuclear Information System (INIS)

    Faizanullah, A.; Bano, A.; Nosheen, A.

    2010-01-01

    A field experiment was conducted to compare the effect of plant growth regulators (PGRs) viz. kinetin (K), chlorocholine chloride (CCC) and salicylic acid (SA) on seed yield, oil content and oil quality of Linseed (Linum usitatissimum L) cv. Chandni with a new perspective to biodiesel production. The growth regulators (10-6M) were applied as seed soaking for 10 h prior to cultivation. Kinetin significantly increased the number of capsules/plant, seed number/capsule, 1000 seed weight and total seed yield (kg/h). The growth regulators increased the seed oil content maximum being in kinetin and CCC treatments. Kinetin and CCC significantly decreased the oil acid value, free fatty acid content (% oleic acid) and increased the pH of oil. Nevertheless, SA significantly decreased the oil specific gravity and did not alter the pH. Only kinetin significantly increased the oil iodine value. The oil extracted from seeds of kinetin and CCC treated plants showed maximum conversion (% w/w) to methyl esters/biodiesel after transesterification. It can be inferred that PGRs can be utilized successfully for improving the biodiesel yield of linseed. (author)

  17. Effects of plant growth regulators in heliconia ‘Red Opal’

    Directory of Open Access Journals (Sweden)

    Ana Cecilia Ribeiro de Castro

    2016-12-01

    Full Text Available The objective of this study was to evaluate growth regulators with purpose of reducing the size of heliconia ‘Red Opal’ potted plants. The experiment was carried out in randomized block design with five treatments (trinexapac-ethyl and paclobutrazol at rates of 37.5 and 75.0 mg of active ingredient per pot and control without growth regulator and five replicates. The treatments were applied 40 days after planting the rhizomes in pots filled with soil. Thirty and 150 days after the growth regulator application, plant height, number of leaves and shoots, petioles length and leaf area were evaluated. One year after planting the rhizomes in pots the number of inflorescence and leaves (leaves, sheathing leaf bases and inflorescences and rhizomes (rhizomes and roots dry mass were determined. Trinexapac-ethyl had no differences compared to the control in any of the variables evaluated. Paclobutrazol proved effective in reducing plant height, leaf area and petiole length and increase in number of leaves and shoots but the effect was temporary. Also, it did not affect the inflorescences production and leaves and rhizomes dry mass. Paclobutrazol is efficient to promote height reduction and to increase the number of shoots in heliconia ‘Red Opal’ potted plants without affect the inflorescence formation but its effects is temporary.

  18. Effect of growth regulators on 'Brookfield' apple gas diffusion and metabolism under controlled atmosphere storage

    Directory of Open Access Journals (Sweden)

    Auri Brackmann

    2014-05-01

    Full Text Available The objective of this work was to evaluate the effect of growth regulators on gas diffusion and on metabolism of 'Brookfield' apple, and to determine their correlation with quality characteristics of fruit stored in controlled atmosphere. A completely randomized design was used with four replicates. After eight months of storage, the effects of water (control, aminoethoxyvinylglycine (AVG, AVG + ethephon, AVG + naphthaleneacetic acid (NAA, ethephon + NAA, sole NAA, 1-MCP, ethylene absorption by potassium permanganate (ABS, AVG + ABS, and of AVG + 1-MCP - applied at different rates and periods - were evaluated on: gas diffusion rate, ethylene production, respiratory rate, internal ethylene concentration, internal CO2 content, mealiness, and intercellular space. Fruit from the control and sole NAA treatments had the highest mealiness occurrence. Growth regulators significantly changed the gaseous diffusion through the pulp of 'Brookfield' apple, mainly in the treatment AVG + ABS, which kept the highest gas diffusion rate. NAA spraying in the field, with or without another growth regulator, increased ripening metabolism by rising ethylene production and respiration rate, and reduced gas diffusion during shelf life. AVG spraying cannot avoid the ethephon effect during the ripening process, and reduces both the internal space and mealiness incidence, but it is not able to induce ethylene production or to increase respiration rates.

  19. Drosophila Big bang regulates the apical cytocortex and wing growth through junctional tension.

    Science.gov (United States)

    Tsoumpekos, Giorgos; Nemetschke, Linda; Knust, Elisabeth

    2018-03-05

    Growth of epithelial tissues is regulated by a plethora of components, including signaling and scaffolding proteins, but also by junctional tension, mediated by the actomyosin cytoskeleton. However, how these players are spatially organized and functionally coordinated is not well understood. Here, we identify the Drosophila melanogaster scaffolding protein Big bang as a novel regulator of growth in epithelial cells of the wing disc by ensuring proper junctional tension. Loss of big bang results in the reduction of the regulatory light chain of nonmuscle myosin, Spaghetti squash. This is associated with an increased apical cell surface, decreased junctional tension, and smaller wings. Strikingly, these phenotypic traits of big bang mutant discs can be rescued by expressing constitutively active Spaghetti squash. Big bang colocalizes with Spaghetti squash in the apical cytocortex and is found in the same protein complex. These results suggest that in epithelial cells of developing wings, the scaffolding protein Big bang controls apical cytocortex organization, which is important for regulating cell shape and tissue growth. © 2018 Tsoumpekos et al.

  20. Effect of Plant Growth Regulators on Leaf Number, Leaf Area and Leaf Dry Matter in Grape

    Directory of Open Access Journals (Sweden)

    Zahoor Ahmad BHAT

    2011-03-01

    Full Text Available Influence of phenylureas (CPPU and brassinosteriod (BR along with GA (gibberellic acid were studied on seedless grape vegetative characteristics like leaf number, leaf area and leaf dry matter. Growth regulators were sprayed on the vines either once (7 days after fruit set or 15 days after fruit set or twice (7+15 days after fruit set. CPPU 2 ppm+BR 0.4 ppm+GA 25 ppm produced maximum number of leaves (18.78 while as untreated vines produced least leaf number (16.22 per shoot. Maximum leaf area (129.70 cm2 and dry matter content (26.51% was obtained with higher CPPU (3 ppm and BR (0.4 ppm combination along with GA 25 ppm. Plant growth regulators whether naturally derived or synthetic are used to improve the productivity and quality of grapes. The relatively high value of grapes justifies more expensive inputs. A relatively small improvement in yield or fruit quality can justify the field application of a very costly product. Application of new generation growth regulators like brassinosteroids and phenylureas like CPPU have been reported to increase the leaf number as well as leaf area and dry matter thereby indirectly influencing the fruit yield and quality in grapes.

  1. Pu-erh Tea Inhibits Tumor Cell Growth by Down-Regulating Mutant p53

    Science.gov (United States)

    Zhao, Lanjun; Jia, Shuting; Tang, Wenru; Sheng, Jun; Luo, Ying

    2011-01-01

    Pu-erh tea is a kind of fermented tea with the incorporation of microorganisms’ metabolites. Unlike green tea, the chemical characteristics and bioactivities of Pu-erh tea are still not well understood. Using water extracts of Pu-erh tea, we analyzed the tumor cell growth inhibition activities on several genetically engineered mouse tumor cell lines. We found that at the concentration that did not affect wild type mouse embryo fibroblasts (MEFs) growth, Pu-erh tea extracts could inhibit tumor cell growth by down-regulated S phase and cause G1 or G2 arrest. Further study showed that Pu-erh tea extracts down-regulated the expression of mutant p53 in tumor cells at the protein level as well as mRNA level. The same concentration of Pu-erh tea solution did not cause p53 stabilization or activation of its downstream pathways in wild type cells. We also found that Pu-erh tea treatment could slightly down-regulate both HSP70 and HSP90 protein levels in tumor cells. These data revealed the action of Pu-erh tea on tumor cells and provided the possible mechanism for Pu-erh tea action, which explained its selectivity in inhibiting tumor cells without affecting wild type cells. Our data sheds light on the application of Pu-erh tea as an anti-tumor agent with low side effects. PMID:22174618

  2. Surface microstructures on planar substrates and textile fibers guide neurite outgrowth: a scaffold solution to push limits of critical nerve defect regeneration?

    Directory of Open Access Journals (Sweden)

    Stefan Weigel

    Full Text Available The treatment of critical size peripheral nerve defects represents one of the most serious problems in neurosurgery. If the gap size exceeds a certain limit, healing can't be achieved. Connection mismatching may further reduce the clinical success. The present study investigates how far specific surface structures support neurite outgrowth and by that may represent one possibility to push distance limits that can be bridged. For this purpose, growth cone displacement of fluorescent embryonic chicken spinal cord neurons was monitored using time-lapse video. In a first series of experiments, parallel patterns of polyimide ridges of different geometry were created on planar silicon oxide surfaces. These channel-like structures were evaluated with and without amorphous hydrogenated carbon (a-C:H coating. In a next step, structured and unstructured textile fibers were investigated. All planar surface materials (polyimide, silicon oxide and a-C:H proved to be biocompatible, i.e. had no adverse effect on nerve cultures and supported neurite outgrowth. Mean growth cone migration velocity measured on 5 minute base was marginally affected by surface structuring. However, surface structure variability, i.e. ridge height, width and inter-ridge spacing, significantly enhanced the resulting net velocity by guiding the growth cone movement. Ridge height and inter-ridge distance affected the frequency of neurites crossing over ridges. Of the evaluated dimensions ridge height, width, and inter-ridge distance of respectively 3, 10, and 10 µm maximally supported net axon growth. Comparable artificial grooves, fabricated onto the surface of PET fibers by using an excimer laser, showed similar positive effects. Our data may help to further optimize surface characteristics of artificial nerve conduits and bioelectronic interfaces.

  3. Graphene quantum dots as enhanced plant growth regulators: effects on coriander and garlic plants.

    Science.gov (United States)

    Chakravarty, Disha; Erande, Manisha B; Late, Dattatray J

    2015-10-01

    We report investigations on the use of graphene quantum dots for growth enhancement in coriander (Coriandrum sativam L.) and garlic (Allium sativum) plants. The as-received seeds of coriander and garlic were treated with 0.2 mg mL(-1) of graphene quantum dots for 3 h before planting. Graphene quantum dots enhanced the growth rate in coriander and garlic plants, including leaves, roots, shoots, flowers and fruits, when the seeds were treated with graphene quantum dots. Our investigations open up the opportunity to use graphene quantum dots as plant growth regulators that can be used in a variety of other food plants for high yield. © 2015 Society of Chemical Industry.

  4. Self-regulating and diameter-selective growth of GaN nanowires

    International Nuclear Information System (INIS)

    Kuo, C-K; Hsu, C-W; Wu, C-T; Lan, Z-H; Mou, C-Y; Chen, C-C; Yang, Y-J; Chen, L-C; Chen, K-H

    2006-01-01

    We report diameter-selective growth of GaN nanowires (NWs) by using mono-dispersed Au nanoparticles (NPs) on a ligand-modified Si substrate. The thiol-terminal silane was found to be effective in producing well-dispersed Au NPs in low density on Si substrates so that the agglomeration of Au NPs during growth could be avoided. The resultant GaN NWs exhibited a narrow diameter distribution and their mean diameter was always larger than, while keeping a deterministic relation with, the size of the Au NPs from which they were grown. A self-regulating steady growth model is proposed to account for the size-control process

  5. Starch as a major integrator in the regulation of plant growth

    Science.gov (United States)

    Sulpice, Ronan; Pyl, Eva-Theresa; Ishihara, Hirofumi; Trenkamp, Sandra; Steinfath, Matthias; Witucka-Wall, Hanna; Gibon, Yves; Usadel, Björn; Poree, Fabien; Piques, Maria Conceição; Von Korff, Maria; Steinhauser, Marie Caroline; Keurentjes, Joost J. B.; Guenther, Manuela; Hoehne, Melanie; Selbig, Joachim; Fernie, Alisdair R.; Altmann, Thomas; Stitt, Mark

    2009-01-01

    Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite profiling in 94 Arabidopsis accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1-phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production. PMID:19506259

  6. LIGHT REGULATION OF GROWTH AND MELANIN FORMATION IN Inonotus оbliquus (Pers. Pilat

    Directory of Open Access Journals (Sweden)

    N. L. Poyedinok

    2013-04-01

    Full Text Available The study aims to investigate possibilities of using different sources of low-intensity light for the regulation of mycelium growth and melanin synthesis by medicinal mushroom Inonotus obliquus (Pers. Pilat. Studies of the light’s influence on the linear growth, biomass accumulation and melanin synthesis I. obliquus were performed using experimental installations that provide both lasing (coherent light with specified parameters, as well as sources of incoherent light. It has been demonstrated that the greatest stimulating effect took place during the irradiation of mycelium with blue light. It has been found that further realization of photobiological effect is largely dependent on the method of cultivation. Irradiation with laser light within all studied wavelength ranges was more conducive to growth, biomass and melanin accumulation in the mushroom mycelium than incoherent light irradiation within the same wavelength range. Light treatment made it possible to significantly reduce the duration of fermentation. The results of studies allow considering lowintensity light in the visible part of the spectrum as a perspective growth and biosynthetic activity regulator of I. obliquus in the biotechnology of its cultivation.

  7. ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

    Science.gov (United States)

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-09-25

    In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. GDP-D-mannose epimerase regulates male gametophyte development, plant growth and leaf senescence in Arabidopsis.

    Science.gov (United States)

    Qi, Tiancong; Liu, Zhipeng; Fan, Meng; Chen, Yan; Tian, Haixia; Wu, Dewei; Gao, Hua; Ren, Chunmei; Song, Susheng; Xie, Daoxin

    2017-09-04

    Plant GDP-D-mannose epimerase (GME) converts GDP-D-mannose to GDP-L-galactose, a precursor of both L-ascorbate (vitamin C) and cell wall polysaccharides. However, the genetic functions of GME in Arabidopsis are unclear. In this study, we found that mutations in Arabidopsis GME affect pollen germination, pollen tube elongation, and transmission and development of the male gametophyte through analysis of the heterozygous GME/gme plants and the homozygous gme plants. Arabidopsis gme mutants also exhibit severe growth defects and early leaf senescence. Surprisingly, the defects in male gametophyte in the gme plants are not restored by L-ascorbate, boric acid or GDP-L-galactose, though boric acid rescues the growth defects of the mutants, indicating that GME may regulate male gametophyte development independent of L-ascorbate and GDP-L-galactose. These results reveal key roles for Arabidopsis GME in reproductive development, vegetative growth and leaf senescence, and suggest that GME regulates plant growth and controls male gametophyte development in different manners.

  9. Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes.

    Science.gov (United States)

    Li, Yuwei; Ahrens, Molly J; Wu, Amy; Liu, Jennifer; Dudley, Andrew T

    2011-01-01

    For tissues that develop throughout embryogenesis and into postnatal life, the generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity. Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways. We present an integrated model for the regulation of proliferation potential by CamkII activity that has important implications for studies of growth control and adult progenitor/stem cell populations.

  10. Self-regulated growth of LaVO3 thin films by hybrid molecular beam epitaxy

    International Nuclear Information System (INIS)

    Zhang, Hai-Tian; Engel-Herbert, Roman; Dedon, Liv R.; Martin, Lane W.

    2015-01-01

    LaVO 3 thin films were grown on SrTiO 3 (001) by hybrid molecular beam epitaxy. A volatile metalorganic precursor, vanadium oxytriisopropoxide (VTIP), and elemental La were co-supplied in the presence of a molecular oxygen flux. By keeping the La flux fixed and varying the VTIP flux, stoichiometric LaVO 3 films were obtained for a range of cation flux ratios, indicating the presence of a self-regulated growth window. Films grown under stoichiometric conditions were found to have the largest lattice parameter, which decreased monotonically with increasing amounts of excess La or V. Energy dispersive X-ray spectroscopy and Rutherford backscattering measurements were carried out to confirm film compositions. Stoichiometric growth of complex vanadate thin films independent of cation flux ratios expands upon the previously reported self-regulated growth of perovskite titanates using hybrid molecular beam epitaxy, thus demonstrating the general applicability of this growth approach to other complex oxide materials, where a precise control over film stoichiometry is demanded by the application

  11. The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKCα activation in SH-SY5Y cells.

    Science.gov (United States)

    Talman, Virpi; Amadio, Marialaura; Osera, Cecilia; Sorvari, Salla; Boije Af Gennäs, Gustav; Yli-Kauhaluoma, Jari; Rossi, Daniela; Govoni, Stefano; Collina, Simona; Ekokoski, Elina; Tuominen, Raimo K; Pascale, Alessia

    2013-07-01

    Protein kinase C (PKC) is a family of serine/threonine phosphotransferases ubiquitously expressed and involved in multiple cellular functions, such as proliferation, apoptosis and differentiation. The C1 domain of PKC represents an attractive drug target, especially for developing PKC activators. Dialkyl 5-(hydroxymethyl)isophthalates are a novel group of synthetic C1 domain ligands that exhibit antiproliferative effect in HeLa cervical carcinoma cells. Here we selected two isophthalates, HMI-1a3 and HMI-1b11, and characterized their effects in the human neuroblastoma cell line SH-SY5Y. Both of the active isophthalates exhibited significant antiproliferative and differentiation-inducing effects. Since HMI-1b11 did not impair cell survival even at the highest concentration tested (20μM), and supported neurite growth and differentiation of SH-SY5Y cells, we focused on studying its downstream signaling cascades and effects on gene expression. Consistently, genome-wide gene expression microarray and gene set enrichment analysis indicated that HMI-1b11 (10μM) induced changes in genes mainly related to cell differentiation. In particular, further studies revealed that HMI-1b11 exposure induced up-regulation of GAP-43, a marker for neurite sprouting and neuronal differentiation. These effects were induced by a 7-min HMI-1b11 treatment and specifically depended on PKCα activation, since pretreatment with the selective inhibitor Gö6976 abolished the up-regulation of GAP-43 protein observed at 12h. In parallel, we found that a 7-min exposure to HMI-1b11 induced PKCα accumulation to the cytoskeleton, an effect that was again prevented by pretreatment with Gö6976. Despite similar binding affinities to PKC, the isophthalates had different effects on PKC-dependent ERK1/2 signaling: HMI-1a3-induced ERK1/2 phosphorylation was transient, while HMI-1b11 induced a rapid but prolonged ERK1/2 phosphorylation. Overall our data are in accordance with previous studies showing that

  12. Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

    Directory of Open Access Journals (Sweden)

    Amélie Avet-Rochex

    2014-09-01

    Full Text Available Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk, which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem

  13. Membrane-localized ubiquitin ligase ATL15 functions in sugar-responsive growth regulation in Arabidopsis.

    Science.gov (United States)

    Aoyama, Shoki; Terada, Saki; Sanagi, Miho; Hasegawa, Yoko; Lu, Yu; Morita, Yoshie; Chiba, Yukako; Sato, Takeo; Yamaguchi, Junji

    2017-09-09

    Ubiquitin ligases play important roles in regulating various cellular processes by modulating the protein function of specific ubiquitination targets. The Arabidopsis Tóxicos en Levadura (ATL) family is a group of plant-specific RING-type ubiquitin ligases that localize to membranes via their N-terminal transmembrane-like domains. To date, 91 ATL isoforms have been identified in the Arabidopsis genome, with several ATLs reported to be involved in regulating plant responses to environmental stresses. However, the functions of most ATLs remain unknown. This study, involving transcriptome database analysis, identifies ATL15 as a sugar responsive ATL gene in Arabidopsis. ATL15 expression was rapidly down-regulated in the presence of sugar. The ATL15 protein showed ubiquitin ligase activity in vitro and localized to plasma membrane and endomembrane compartments. Further genetic analyses demonstrated that the atl15 knockout mutants are insensitive to high glucose concentrations, whereas ATL15 overexpression depresses plant growth. In addition, endogenous glucose and starch amounts were reciprocally affected in the atl15 knockout mutants and the ATL15 overexpressors. These results suggest that ATL15 protein plays a significant role as a membrane-localized ubiquitin ligase that regulates sugar-responsive plant growth in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer

    Science.gov (United States)

    Cekaite, Lina; Eide, Peter W.; Lind, Guro E.; Skotheim, Rolf I.; Lothe, Ragnhild A.

    2016-01-01

    Gene expression is in part regulated by microRNAs (miRNAs). This review summarizes the current knowledge of miRNAs in colorectal cancer (CRC); their role as growth regulators, the mechanisms that regulate the miRNAs themselves and the potential of miRNAs as biomarkers. Although thousands of tissue samples and bodily fluids from CRC patients have been investigated for biomarker potential of miRNAs (>160 papers presented in a comprehensive tables), none single miRNA nor miRNA expression signatures are in clinical use for this disease. More than 500 miRNA-target pairs have been identified in CRC and we discuss how these regulatory nodes interconnect and affect signaling pathways in CRC progression. PMID:26623728

  15. Post-transcriptional regulation of vascular endothelial growth factor: Implications for tumor angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Peter S Yoo; Abby L Mulkeen; Charles H Cha

    2006-01-01

    Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization,translation, and differential cellular localization of various isoforms. Recent advances in our understanding of posttranscriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi)technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.

  16. Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in Drosophila.

    Science.gov (United States)

    Wen, Jung-Kun; Wang, Yi-Ting; Chan, Chih-Chiang; Hsieh, Cheng-Wen; Liao, Hsiao-Man; Hung, Chin-Chun; Chen, Guang-Chao

    2017-11-16

    Autophagy is essential for maintaining cellular homeostasis and survival under various stress conditions. Autophagy-related gene 9 (Atg9) encodes a multipass transmembrane protein thought to act as a membrane carrier for forming autophagosomes. However, the molecular regulation and physiological importance of Atg9 in animal development remain largely unclear. Here, we generated Atg9 null mutant flies and found that loss of Atg9 led to shortened lifespan, locomotor defects, and increased susceptibility to stress. Atg9 loss also resulted in aberrant adult midgut morphology with dramatically enlarged enterocytes. Interestingly, inhibiting the TOR signaling pathway rescued the midgut defects of the Atg9 mutants. In addition, Atg9 interacted with PALS1-associated tight junction protein (Patj), which associates with TSC2 to regulate TOR activity. Depletion of Atg9 caused a marked decrease in TSC2 levels. Our findings revealed an antagonistic relationship between Atg9 and TOR signaling in the regulation of cell growth and tissue homeostasis.

  17. Effects of photoperiod, plant growth regulators and culture media on in vitro growth of seedlings of Cyrtochilum loxense (Lindl. Kraenzl. an endemic and endangered orchid from Ecuador

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    Yadira González

    2014-10-01

    Full Text Available Cyrtochilum loxense (Lindl. Kraenzl. is an endemic and seriously endangered orchid species endemic in the Loja Province (Southern Ecuador. The main goals of this research were to analyze how culture media, plant growth regulators and photoperiod affect the growth of C. loxense. Eight month old plants (approximate 1 – 1.5 cm in height obtained by in vitro germination, were cultivated on MS media or Knudson C; MS with three levels of naphthalene acetic acid (NAA and 6-benzylaminopurine (BAP (2/0.5; 1/0.5 y 0.5/ 0.5 mg-1L; and three photoperiodic regimes (24/0, 16/8, 8/16 h on MS with and without plant growth regulators. No significant differences of shoot induction were observed on media with or without plant growth regulators, and all tested photoperiods. The highest growth (1.2 cm was observed in plantlets cultivated on growth regulator-free media with a 16/8 photoperiod. Also the shoot and root formation was better in this species in absence of plant growth regulators. Probably this response is due to the endogenous hormone levels in the tissues or due to the kind and concentrations of PGRs used were too low to induce positive morphogenetic responses.

  18. Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2

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    D'Orazi Gabriella

    2008-07-01

    Full Text Available Abstract Background Homeodomain-interacting protein kinase-2 (HIPK2 plays an essential role in restraining tumor progression as it may regulate, by itself or within multiprotein complexes, many proteins (mainly transcription factors involved in cell growth and apoptosis. This study takes advantage of the recent finding that HIPK2 may repress the β-catenin transcription activity. Thus, we investigated whether HIPK2 overexpression may down-regulate vascular endothelial growth factor (VEGF levels (a β-catenin target gene and the role of β-catenin in this regulation, in order to consider HIPK2 as a tool for novel anti-tumoral therapeutical approaches. Methods The regulation of VEGF expression by HIPK2 was evaluated by using luciferase assay with VEGF reporter construct, after overexpression of the β-catenin transcription factor. Relative quantification of VEGF and β-catenin mRNAs were assessed by reverse-transcriptase-PCR (RT-PCR analyses, following HIPK2 overexpression, while β-catenin protein levels were evaluated by western immunoblotting. Results HIPK2 overexpression in tumor cells downregulated VEGF mRNA levels and VEGF promoter activity. The VEGF downregulation was partly depending on HIPK2-mediated β-catenin regulation. Thus, HIPK2 could induce β-catenin protein degradation that was prevented by cell treatment with proteasome inhibitor MG132. The β-catenin degradation was dependent on HIPK2 catalytic activity and independent of p53 and glycogen synthase kinase 3β (GSK-3β activities. Conclusion These results suggest that VEGF might be a target of HIPK2, at least in part, through regulation of β-catenin activity. These findings support the function of HIPK2 as tumor suppressor and hypothesise a role for HIPK2 as antiangiogenic tool in tumor therapy approaches.

  19. [Effectiveness of three biological larvicides and of an insect growth regulator against Anopheles arabiensis in Senegal].

    Science.gov (United States)

    Diédhiou, S M; Konaté, L; Doucouré, S; Samb, B; Niang, E A; Sy, O; Thiaw, O; Konaté, A; Wotodjo, A N; Diallo, M; Gadiaga, L; Sokhna, C; Faye, O

    2017-05-01

    Urban malaria is a major public health problem in Africa. In Senegal, the environmental changes seem to favor the persistence of malaria transmission in Dakar suburbs by creating, throughout the year, potential breeding sites of malaria vectors. In such a situation and in a context of a growing threat of insecticide resistance in anopheline vectors, the larval control making use of products from biological origin or growth regulators could represent an additional tool to the current strategies developed against anophelines. In this study conducted in 2012, the efficiency and residual effect of three biological larvicides (VectoBac ® WG, Vecto-Max ® CG, and VectoBac ® GR) and an insect growth regulator (MetaLarv™) were evaluated on Anopheles gambiae s.l. larvae in seminatural conditions (experimental station) and natural breeding sites in the suburbs of Dakar. The formulations were tested according to the manufacturer recommendations, namely 0.03 g/m 2 for VectoBac ® WG, 0.5 g/m 2 for VectoBac ® GR, 0.75 g/m 2 for VectoMax ® CG, and 0.5 g/m 2 for MetaLarv™. In experimental station, the treatment with larvicides was effective over a period of 14 days with a mortality ranging between 92% and 100%. The insect growth regulator remained effective up to 55 days with a single emergence recorded in the 27th day after treatment. In natural conditions, a total effectiveness (100% mortality) of larvicides was obtained 48 hours after treatment, then a gradual recolonization of breeding sites was noted. However, the insect growth regulator has reduced adult emergence higher than 80% until the end of follow-up (J28). This study showed a good efficiency of the larvicides and of the growth regulator tested. These works provide current data on potential candidates for the implementation of larval control interventions in addition to that of chemical adulticide for control of urban malaria.

  20. LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.

    Science.gov (United States)

    Takano, Tetsuya; Urushibara, Tomoki; Yoshioka, Nozomu; Saito, Taro; Fukuda, Mitsunori; Tomomura, Mineko; Hisanaga, Shin-Ichi

    2014-06-01

    Neurons extend two types of neurites-axons and dendrites-that differ in structure and function. Although it is well understood that the cytoskeleton plays a pivotal role in neurite differentiation and extension, the mechanisms by which membrane components are supplied to growing axons or dendrites is largely unknown. We previously reported that the membrane supply to axons is regulated by lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the role of LMTK1 in dendrite formation. Down-regulation of LMTK1 increases dendrite growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1 knockout significantly enhances the prevalence, velocity, and run length of anterograde movement of Rab11A-positive endosomes to levels similar to those expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics also increases in the cell body and growth cone of LMTK1-deficient neurons. Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth. © 2014 Takano et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. Influence of Plant Growth Regulators (PGRs and Planting Method on Growth and Yield in Oil Pumpkin (Cucurbita pepo var. styriaca

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    Shirzad SURE

    2012-05-01

    Full Text Available The effect of plant growth regulators IBA (indole butyric acid, GA3 (gibberellin and ethylene (as ethephon in two methods of planting was investigated (each method was considered as a separate experiment on morphological characters and yield of medicinal pumpkin. The experiments were carried out in a factorial trial based on completely randomized block design, with four replicates. The treatments were combined with priming and spraying with the above PGRs. The first seed priming with control (water, IBA 100 ppm, GA3 25 ppm and ethephon 200 ppm, and when seedling developed to 4 leaf stage sprayed there with control (water, IBA 100 ppm, GA3 25 ppm and ethephon 200 ppm for three times. In both planting methods, there were all of these treatments. The result showed that PGRs and planting method had significant effects on vegetative, flowering and yield characteristics including: leaf area %DM plant, number of male and female flowers per plant, number of fruit/plant, fruits fresh weight, seeds length and width, number of seed per fruit, seed yield, % seeds oil and oil yield. Hence spraying with GA3 25 ppm in four leaf stage at trellis method could be a suitable treatment for enhancing growth and yield of medicinal pumpkin.

  2. Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.

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    Patrick Fischer

    2015-08-01

    Full Text Available In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP. Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E, is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb, the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila.

  3. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.

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    Robert W Tilghman

    Full Text Available Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa, cells on soft substrates (150-300 Pa exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins and glycolysis (e.g., phosphofructokinase-1, whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical

  4. Predominant role of water in regulating the tree-growth response to diurnal asymmetric warmin

    Science.gov (United States)

    Chen, Z.; Xia, J.; Cui, E.

    2017-12-01

    Growth of the Northern Hemisphere trees is affected by diurnal asymmetric warming, which is generally considered to touch off carbon assimilation and increment of carbon storage. Asymmetric effects of diurnal warming on vegetation greenness were validated in previous researches, however, the effect of diurnal warming on wood tissue which stores most carbon of a whole plant is still unknown. Here, we combined ring-width index (RWI), remote sensing-based normalized difference vegetation index (NDVI) and climate datasets to detect the effects of daytime and night-time warming on vegetation growth, respectively. Our results indicate that daytime warming enhances NDVI but has neutral effect on tree woody growth over the Northern Hemisphere. Response of wood growth to daytime warming is linearly regulated by soil water availability. The underlying mechanism of different response of canopy and wood growth to daytime warming may attribute to the biomass change, that is, allocation to foliage tissues increased at the expense of wood tissue under warming and water-limited conditions. Night-time warming show neutral effects on NDVI and RWI over the Northern Hemisphere, and the neutral Tmin-NDVI correlations result from the non-linear mediation of soil water availability. Our results highlight the current greening trend under daytime warming does not mean higher carbon sink capacity, the warming-drying climate may impair the large carbon sink of global forests.

  5. N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

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    Giorgi Kharebava

    2015-12-01

    Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

  6. The role of nitrogen and phosphorus in regulating Phormidium sp. (cyanobacteria) growth and anatoxin production.

    Science.gov (United States)

    Heath, Mark; Wood, Susie A; Young, Roger G; Ryan, Ken G

    2016-03-01

    Benthic proliferations of the cyanobacteria Phormidium can cover many kilometres of riverbed. Phormidium can produce neurotoxic anatoxins and ingestion of benthic mats has resulted in numerous animal poisonings in the last decade. Despite this, there is a poor understanding of the environmental factors regulating growth and anatoxin production. In this study, the effects of nitrogen and phosphorus on the growth of two Phormidium strains (anatoxin-producing and non-anatoxin-producing) were examined in batch monocultures. Cell concentrations were significantly reduced under reduced nitrogen (ca. production. Cellular anatoxin concentrations were lowest (169 fg cell(-1)) under the high-nitrogen and high-phosphorus treatment. This supports the growth-differentiation balance hypothesis that suggests actively dividing and expanding cells are less likely to produce secondary-metabolites. Anatoxin quota was highest (>407 fg cell(-1)) in the reduced phosphorus treatments, possibly suggesting that it is produced as a stress response to growth limiting conditions. In all treatments there was a 4-5-fold increase in anatoxin quota in the lag growth phase, possibly indicating it may provide a physiological benefit during initial substrate colonization. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Leptin differentially regulates chondrogenesis in mouse vertebral and tibial growth plates.

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    Yu, Bo; Jiang, Kaibiao; Chen, Bin; Wang, Hantao; Li, Xinfeng; Liu, Zude

    2017-05-31

    Leptin plays an important role in mediating chondrogenesis of limb growth plate. Previous studies suggest that bone structures and development of spine and limb are different. The expression of Ob-Rb, the gene that encodes leptin receptors, is vertebral and appendicular region-specific, suggesting the regulation of leptin on VGP and TGP chondrogenesis may be very different. The aim of the present study was to investigate the differential regulation of leptin on the chondrogenesis of vertebral growth plate (VGP) and tibial growth plate (TGP). We compared the VGP and TGP from wild type (C57BL/6) and leptin-deficient (ob/ob) mice. We then generated primary cultures of TGP and VGP chondrocytes. By treating the primary cells with different concentrations of leptin in vitro, we analyzed proliferation and apoptosis of the primary chondrocytes from TGP and VGP. We further measured expression of chondrogenic-related genes in these cells that had been incubated with different doses of leptin. Leptin-deficient mice of 8-week-old had shorter tibial and longer vertebral lengths than the wide type mice. Disturbed columnar structure was observed for TGP but not for VGP. In primary chondrocyte cultures, leptin inhibited VGP chondrocyte proliferation but promoted their apoptosis. Collagen IIA and aggrecan mRNA, and the protein levels of proliferation- and chondrogenesis-related markers, including PCNA, Sox9, and Smad4, were downregulated by leptin in a dose-dependent manner. In contrast, leptin stimulated the proliferation and chondrogenic differentiation of TGP chondrocytes at physiological levels (i.e., 10 and 50 ng/mL) but not at high levels (i.e., 100 and 1000 ng/mL). Leptin exerts a stimulatory effect on the proliferation and chondrogenic differentiation of the long bone growth plate but an inhibitory effect on the spine growth plate. The ongoing study will shed light on the regulatory mechanisms of leptin in bone development and metabolism.

  8. The yeast Sks1p kinase signaling network regulates pseudohyphal growth and glucose response.

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    Cole Johnson

    2014-03-01

    Full Text Available The yeast Saccharomyces cerevisiae undergoes a dramatic growth transition from its unicellular form to a filamentous state, marked by the formation of pseudohyphal filaments of elongated and connected cells. Yeast pseudohyphal growth is regulated by signaling pathways responsive to reductions in the availability of nitrogen and glucose, but the molecular link between pseudohyphal filamentation and glucose signaling is not fully understood. Here, we identify the glucose-responsive Sks1p kinase as a signaling protein required for pseudohyphal growth induced by nitrogen limitation and coupled nitrogen/glucose limitation. To identify the Sks1p signaling network, we applied mass spectrometry-based quantitative phosphoproteomics, profiling over 900 phosphosites for phosphorylation changes dependent upon Sks1p kinase activity. From this analysis, we report a set of novel phosphorylation sites and highlight Sks1p-dependent phosphorylation in Bud6p, Itr1p, Lrg1p, Npr3p, and Pda1p. In particular, we analyzed the Y309 and S313 phosphosites in the pyruvate dehydrogenase subunit Pda1p; these residues are required for pseudohyphal growth, and Y309A mutants exhibit phenotypes indicative of impaired aerobic respiration and decreased mitochondrial number. Epistasis studies place SKS1 downstream of the G-protein coupled receptor GPR1 and the G-protein RAS2 but upstream of or at the level of cAMP-dependent PKA. The pseudohyphal growth and glucose signaling transcription factors Flo8p, Mss11p, and Rgt1p are required to achieve wild-type SKS1 transcript levels. SKS1 is conserved, and deletion of the SKS1 ortholog SHA3 in the pathogenic fungus Candida albicans results in abnormal colony morphology. Collectively, these results identify Sks1p as an important regulator of filamentation and glucose signaling, with additional relevance towards understanding stress-responsive signaling in C. albicans.

  9. Growth in Adolescent Self-Regulation and Impact on Sexual Risk-Taking: A Curve-of-Factors Analysis.

    Science.gov (United States)

    Crandall, AliceAnn; Magnusson, Brianna M; Novilla, M Lelinneth B

    2018-04-01

    Adolescent self-regulation is increasingly seen as an important predictor of sexual risk-taking behaviors, but little is understood about how changes in self-regulation affect later sexual risk-taking. Family financial stress may affect the development of self-regulation and later engagement in sexual risk-taking. We examined whether family financial stress influences self-regulation in early adolescence (age 13) and growth in self-regulation throughout adolescence (from age 13-17 years). We then assessed the effects of family financial stress, baseline self-regulation, and the development of self-regulation on adolescent sexual risk-taking behaviors at age 18 years. Using a curve-of-factors model, we examined these relationships in a 6-year longitudinal study of 470 adolescents (52% female) and their parents from a large northwestern city in the United States. Results indicated that family financial stress was negatively associated with baseline self-regulation but not with growth in self-regulation throughout adolescence. Both baseline self-regulation and growth in self-regulation were predictive of decreased likelihood of engaging in sexual risk-taking. Family financial stress was not predictive of later sexual risk-taking. Intervening to support the development of self-regulation in adolescence may be especially protective against later sexual risk-taking.

  10. Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men.

    Science.gov (United States)

    Sjögren, Klara; Leung, Kin-Chuen; Kaplan, Warren; Gardiner-Garden, Margaret; Gibney, James; Ho, Ken K Y

    2007-07-01

    Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences.

  11. Synchronization of developmental processes and defense signaling by growth regulating transcription factors.

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    Jinyi Liu

    Full Text Available Growth regulating factors (GRFs are a conserved class of transcription factor in seed plants. GRFs are involved in various aspects of tissue differentiation and organ development. The implication of GRFs in biotic stress response has also been recently reported, suggesting a role of these transcription factors in coordinating the interaction between developmental processes and defense dynamics. However, the molecular mechanisms by which GRFs mediate the overlaps between defense signaling and developmental pathways are elusive. Here, we report large scale identification of putative target candidates of Arabidopsis GRF1 and GRF3 by comparing mRNA profiles of the grf1/grf2/grf3 triple mutant and those of the transgenic plants overexpressing miR396-resistant version of GRF1 or GRF3. We identified 1,098 and 600 genes as putative targets of GRF1 and GRF3, respectively. Functional classification of the potential target candidates revealed that GRF1 and GRF3 contribute to the regulation of various biological processes associated with defense response and disease resistance. GRF1 and GRF3 participate specifically in the regulation of defense-related transcription factors, cell-wall modifications, cytokinin biosynthesis and signaling, and secondary metabolites accumulation. GRF1 and GRF3 seem to fine-tune the crosstalk between miRNA signaling networks by regulating the expression of several miRNA target genes. In addition, our data suggest that GRF1 and GRF3 may function as negative regulators of gene expression through their association with other transcription factors. Collectively, our data provide new insights into how GRF1 and GRF3 might coordinate the interactions between defense signaling and plant growth and developmental pathways.

  12. The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Wang, Hong X; Konopka, James B

    2013-11-26

    Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

  13. Nutritive values of brassica campestris L. oil as affected by growth regulator treatments

    International Nuclear Information System (INIS)

    Bano, A.; Khan, N.

    2009-01-01

    The effects of plant growth regulators, viz. Indole acetic acid (IAA), Gibberellic acid (GA) and Abscisic acid (ABA) were studied on fatty acid compositions, glucosinolate content and protein content of Brassica campestris L subsp. Oleifera (common name yellow sarson). Growth regulators were applied in seed soaking solution as well as foliar spray during vegetative phase and at flowering stage. There were reductions in the amount of long chain fatty acids viz erucic acid, eicosenoic acid and increase in the amount of unsaturated fatty acid viz. linoleic acid by lAA applications. The stimulating effect of lAA which reduced amount of unsaturated fatty acid was more pronounced when applied as foliar spray at vegetative stage. But, foliar spray of ABA during flowering increased the concentration of linoleic acid and reduced the eicosenoic acid and erucic acid. The glucosinolate content was greater in seeds soaked in 10/sup -5/ M lAA than that of control but less in 10/sup -5/ M GA treated seeds than that of control. The ABA treatment (10/sup -5/M) increased the concentration of glucosinolates in the seeds IAA treatments (10/sup -5/M) increased the protein percentage in the seeds. Foliar application of GA (10/sup -5/M) during vegetative growth and ABA (10/sup -5/M) as seed soaking prior to sowing as well as foliar spry during flowering decreased the protein content of seeds. (author)

  14. Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

    International Nuclear Information System (INIS)

    Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

    1986-01-01

    The specific binding of iodinated epidermal growth factor ([ 125 I]iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites [dissociation constant (Kd) = 0.7-1.8 nM]. Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status

  15. Role of endogenous growth regulators in vernalization of seeds of radish (Raphanus sativus L.

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    Marian Michniewicz

    2014-01-01

    Full Text Available In embryos and cotyledons of seeds of the radish cv. `Tetra Iłówiecka' (which needs 20 days of vernalization and cv. 'Saxa' (which flowers without vernalization germinating at a vernalizing temperature of 5°C, the levels of auxins, gibberellins, cytokinins and the aibscisic acid-like inhibitor were determined, The analyses were performed after 5, 10, 15, 20, 25 and 30 days of chilling. The levels of growth regulators were also determined in embryos and cotyledons of seeds germinated at 260C when in the same growth stage as the material taken from chilled seeds. Cold treatment significantly affected the level of all endogenous growth regulators in embryos and cotyledons of both varieties. However, changes in the levels of these substances were not directly connected with the vernalization process. It was found that the vernalization of seeds of 'the radish cv. `Tetra Iłówiecka' increased the level of GAs in leaves, this did not, however, coincide with flower initiation. It is concluded that the role of GAs in flowering of the studied plants is connected rather with photoinduction than with vernalization.

  16. Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

    Directory of Open Access Journals (Sweden)

    Inês Gomes Ferreira

    2018-02-01

    Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

  17. Dicer-like Proteins Regulate the Growth, Conidiation, and Pathogenicity of Colletotrichum gloeosporioides from Hevea brasiliensis

    Directory of Open Access Journals (Sweden)

    Qiannan Wang

    2018-01-01

    Full Text Available Colletotrichum gloeosporioides from Hevea brasiliensis is the hemibiotrophic fungi which could cause anthracnose in rubber trees. Dicer like proteins (DCL were the core enzymes for generation of small RNAs. In the present study, the knocking-out mutants of two dicer like proteins encoding genes of C. gloeosporioides were constructed; and functions of two proteins were investigated. The results showed that DCL play important roles in regulating the growth, conidiation and pathogenicity of C. gloeosporioides; and there is a functional redundancy between DCL1 and DCL2. Microscopy analysis and DAB staining revealed that loss of penetration ability into the host cells, instead of the decreased growth rate, was the main cause for the impaired pathogenicity of the ΔDcl1ΔDcl2 double mutant. Proteomics analysis suggested that DCL proteins affected the expression of functional proteins to regulating multiple biological processes of C. gloeosporioides. These data lead to a better understanding of the functions of DCL proteins in regulating the development and pathogenesis of C. gloeosporioides.

  18. Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

    Directory of Open Access Journals (Sweden)

    Leandro eFernandez-Perez

    2013-06-01

    Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  19. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage

    Science.gov (United States)

    Garrison, Presley; Yue, Shanna; Hanson, Jeffrey; Baron, Jeffrey; Lui, Julian C.

    2017-01-01

    Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers—the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may

  20. Oligosaccharins, brassinolides, and jasmonates: nontraditional regulators of plant growth, development, and gene expression.

    Science.gov (United States)

    Creelman, R A; Mullet, J E

    1997-07-01

    Each of the nontraditional plant hormones reviewed in this article, oligosaccharins, brassinolides, and JA, can exert major effects on plant growth and development. However, in many cases, the mechanisms by which these compounds are involved in the endogenous regulation of morphogenesis remain to be established. Nevertheless, the use of mutant or transgenic plants with altered levels or perception of these hormones is leading to phenomenal increases in our understanding of the roles they play in the life cycle of plants. It is likely that in the future, novel modulators of plant growth and development will be identified; some will perhaps be related to the peptide encoded by ENOD40 (Van de Sande et al., 1996), which modifies the action of auxin.

  1. The apical scaffold big bang binds to spectrins and regulates the growth of Drosophila melanogaster wing discs.

    Science.gov (United States)

    Forest, Elodie; Logeay, Rémi; Géminard, Charles; Kantar, Diala; Frayssinoux, Florence; Heron-Milhavet, Lisa; Djiane, Alexandre

    2018-03-05

    During development, cell numbers are tightly regulated, ensuring that tissues and organs reach their correct size and shape. Recent evidence has highlighted the intricate connections between the cytoskeleton and the regulation of the key growth control Hippo pathway. Looking for apical scaffolds regulating tissue growth, we describe that Drosophila melanogaster big bang (Bbg), a poorly characterized multi-PDZ scaffold, controls epithelial tissue growth without affecting epithelial polarity and architecture. bbg -mutant tissues are smaller, with fewer cells that are less apically constricted than normal. We show that Bbg binds to and colocalizes tightly with the β-heavy-Spectrin/Kst subunit at the apical cortex and promotes Yki activity, F-actin enrichment, and the phosphorylation of the myosin II regulatory light chain Spaghetti squash. We propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex, where Bbg promotes actomyosin contractility to regulate epithelial tissue growth. © 2018 Forest et al.

  2. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

    Science.gov (United States)

    Brown, Laura D.

    2014-01-01

    Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present for the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts development of muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or “catch up” postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts towards improving muscle growth early in life in order to prevent the development of chronic metabolic disease later in life. PMID:24532817

  3. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Seung Min, E-mail: smjeong@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Hwang, Sunsook; Seong, Rho Hyun [School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2016-03-11

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  4. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    International Nuclear Information System (INIS)

    Jeong, Seung Min; Hwang, Sunsook; Seong, Rho Hyun

    2016-01-01

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  5. Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

    Science.gov (United States)

    Casey, F P; Baird, D; Feng, Q; Gutenkunst, R N; Waterfall, J J; Myers, C R; Brown, K S; Cerione, R A; Sethna, J P

    2007-05-01

    We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

  6. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells

    International Nuclear Information System (INIS)

    Anisowicz, A.; Bardwell, L.; Sager, R.

    1987-01-01

    Comparison by subtractive hybridization of mRNAs revealed a moderately abundant message in highly tumorigenic CHEF/16 cells present at very low levels in closely related nontumorigenic CHEF/18 cells. After cloning and sequencing the corresponding cDNA, computer comparison showed closest homology with the human connective tissue-activating peptide III (CTAP III). The human tumor cell cDNA hybridizing with the Chinese hamster clone was isolated, sequenced, and found to have closer similarity to the Chinese hamster gene than to CTAP III. Thus, the cloned cDNAs from Chinese hamster and human cells represent a different gene, named gro. Studies of its transcriptional regulation have shown that expression is tightly regulated by growth status in normal Chinese hamster and human cells and relaxed in the tumorigenic cells so far examined

  7. The regulation of function, growth and survival of GLP-1-producing L-cells

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Holst, Jens Juul; Kappe, Camilla

    2016-01-01

    that regulate the growth, survival and function of these cells are largely unknown. We recently showed that prolonged exposure to high concentrations of the fatty acid palmitate induced lipotoxic effects, similar to those operative in insulin-producing cells, in an in vitro model of GLP-1-producing cells...... absorption and disposal, as well as cell proliferation and survival. In Type 2 Diabetes (T2D) reduced plasma levels of GLP-1 have been observed, and plasma levels of GLP-1, as well as reduced numbers of GLP-1 producing cells, have been correlated to obesity and insulin resistance. Increasing endogenous...... secretion of GLP-1 by selective targeting of the molecular mechanisms regulating secretion from the L-cell has been the focus of much recent research. An additional and promising strategy for enhancing endogenous secretion may be to increase the L-cell mass in the intestinal epithelium, but the mechanisms...

  8. Regulation of the ligand-dependent activation of the epidermal growth factor receptor by calmodulin

    DEFF Research Database (Denmark)

    Li, Hongbing; Panina, Svetlana; Kaur, Amandeep

    2012-01-01

    Calmodulin (CaM) is the major component of calcium signaling pathways mediating the action of various effectors. Transient increases in the intracellular calcium level triggered by a variety of stimuli lead to the formation of Ca2+/CaM complexes, which interact with and activate target proteins....... In the present study the role of Ca2+/CaM in the regulation of the ligand-dependent activation of the epidermal growth factor receptor (EGFR) has been examined in living cells. We show that addition of different cell permeable CaM antagonists to cultured cells or loading cells with a Ca2+ chelator inhibited...

  9. Bioefficacy of Insect Growth Regulators Against Aedes albopictus (Diptera: Culicidea) From Sarawak, Malaysia: A Statewide Survey.

    Science.gov (United States)

    Lau, Koon Weng; Chen, Chee Dhang; Lee, Han Lim; Low, Van Lun; Sofian-Azirun, Mohd

    2018-05-28

    The susceptibility status of Aedes albopictus (Skuse; Diptera: Culicidea) larvae collected from 13 districts in Sarawak state, Malaysia was evaluated against five insect growth regulators (IGRs) namely, methoprene, pyriproxyfen, diflubenzuron, cyromazine, and novaluron. Field populations of Ae. albopictus were susceptible to methoprene, pyriproxyfen, cyromazine and novaluron with resistance ratios (RRs) ranging from 0.19-0.38, 0.05-0.14, 0.50-0.95, and 0.75-1.00, respectively. Nevertheless, tolerance towards diflubenzuron (0.33-1.33) was observed in this study. In general, these IGRs exhibited promising results and can be used as alternative control agents against field populations of Ae. albopictus in Sarawak, Malaysia.

  10. SH2B Regulation of Growth, Metabolism, and Longevity in Both Insects and Mammals

    OpenAIRE

    Song, Wei; Ren, Decheng; Li, Wenjun; Jiang, Lin; Cho, Kae Won; Huang, Ping; Fan, Chen; Song, Yiyun; Liu, Yong; Rui, Liangyou

    2010-01-01

    SH2B1 is a key regulator of body weight in mammals. Here we identified dSH2B as the Drosophila homolog of SH2B1. dSH2B bound to Chico and directly promoted insulin-like signaling. Disruption of dSH2B decreased insulin-like signaling and somatic growth in flies. dSH2B deficiency also increased hemolymph carbohydrate levels, whole body lipid levels, lifespan, and resistance to starvation and oxidative stress. Systemic overexpression of dSH2B resulted in opposite phenotypes. dSH2B overexpression...

  11. EFFECT OF GROWTH REGULATOR MICEFIT ON YIELD OF GARDEN RADISH (RAPHANUS SATIVUS L.

    Directory of Open Access Journals (Sweden)

    T. M. Seredin

    2015-01-01

    Full Text Available Micefit is a product developed based on mycorrhizal fungi extracted from roots of swamp ledum. For ecological purposes the Micefit is used for final stage of cleaning of contaminated and polluted land at seed sowing and seedling plating. The effect of growth regulator Micefit on seeds of garden radish depending on different concentrations and exposures. The dependence of garden radish yield on time of treatment and concentration is shown.

  12. Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer

    Science.gov (United States)

    2008-10-01

    fibroblast growth factor signaling is down-regulated in prostate cancer. Kwabi-Addo B (2004) Orlando, FL (Oral; mini symposium). • AACR/NCI/EORTC...contains a classic signal peptide PP FRS2 Sos Grb2 Cbl Ras FGFR1-DN MEK ERK STAT3 STAT3 Sprouty PLC - Extracellular stimulus Nucleus P Raf PI3K Receptor... thesis system for reverse transcription-PCR and according to the manufactur- er’s protocol. Real-time PCR was carried out in a Bio-Rad iCycler real

  13. Key role of the kidney in the regulation of fibroblast growth factor 23

    DEFF Research Database (Denmark)

    Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob

    2015-01-01

    was significantly increased in BNX rats. The rapid rise in FGF23 after BNX was independent of parathyroid hormone or FGF receptor signaling. No evidence of early stimulation of FGF23 gene expression in the bone was found. Furthermore, acute severe hyperphosphatemia or hypercalcemia had no impact on intact FGF23......High circulating levels of fibroblast growth factor 23 (FGF23) have been demonstrated in kidney failure, but mechanisms of this are not well understood. Here we examined the impact of the kidney on the early regulation of intact FGF23 in acute uremia as induced by bilateral or unilateral...

  14. Carotenoid content of husk tomato under the influence of growth regulators and gamma rays

    International Nuclear Information System (INIS)

    Raghava, R.P.; Raghava, Nisha

    1990-01-01

    The present studies were conducted to study the effect of growth regulators and gamma rays on carotenoid content in husk tomato (Physalis peruviana L. and P. angulata L.). Results indicated that carotenoid content (in fruits) increased in all the treatments (except 200 and 500 ppm coumarin in case of P. peruviana and 100, 200 and 500 ppm coumarin in case of P. angulata). It is concluded that low doses of gamma rays may show stimulatory effect on carotenoid content in fruits of husk tomato. (author). 10 refs., 1 tab

  15. The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.

    Science.gov (United States)

    Tanimoto, Ryuta; Palladino, Chiara; Xu, Shi-Qiong; Buraschi, Simone; Neill, Thomas; Gomella, Leonard G; Peiper, Stephen C; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2017-12-01

    Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis. Copyright © 2017. Published by Elsevier B.V.

  16. Feast and Famine: regulation of black hole growth in low-redshift galaxies

    Science.gov (United States)

    Kauffmann, Guinevere; Heckman, Timothy M.

    2009-07-01

    We analyse the observed distribution of Eddington ratios (L/LEdd) as a function of supermassive black hole mass for a large sample of nearby galaxies drawn from the Sloan Digital Sky Survey. We demonstrate that there are two distinct regimes of black hole growth in nearby galaxies. The first is associated with galaxies with significant star formation [M*/starformationrate (SFR) ~ a Hubble time] in their central kiloparsec regions, and is characterized by a broad lognormal distribution of accretion rates peaked at a few per cent of the Eddington limit. In this regime, the Eddington ratio distribution is independent of the mass of the black hole and shows little dependence on the central stellar population of the galaxy. The second regime is associated with galaxies with old central stellar populations (M*/SFR >> a Hubble time), and is characterized by a power-law distribution function of Eddington ratios. In this regime, the time-averaged mass accretion rate on to black holes is proportional to the mass of stars in the galaxy bulge, with a constant of proportionality that depends on the mean stellar age of the stars. This result is once again independent of black hole mass. We show that both the slope of the power law and the decrease in the accretion rate on to black holes in old galaxies are consistent with population synthesis model predictions of the decline in stellar mass loss rates as a function of mean stellar age. Our results lead to a very simple picture of black hole growth in the local Universe. If the supply of cold gas in a galaxy bulge is plentiful, the black hole regulates its own growth at a rate that does not further depend on the properties of the interstellar medium. Once the gas runs out, black hole growth is regulated by the rate at which evolved stars lose their mass.

  17. Brassinosteroids regulate pavement cell growth by mediating BIN2-induced microtubule stabilization.

    Science.gov (United States)

    Liu, Xiaolei; Yang, Qin; Wang, Yuan; Wang, Linhai; Fu, Ying; Wang, Xuelu

    2018-02-23

    Brassinosteroids (BRs), a group of plant steroid hormones, play important roles in regulating plant development. The cytoskeleton also affects key developmental processes and a deficiency in BR biosynthesis or signaling leads to abnormal phenotypes similar to those of microtubule-defective mutants. However, how BRs regulate microtubule and cell morphology remains unknown. Here, using liquid chromatography-tandem mass spectrometry, we identified tubulin proteins that interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative regulator of BR responses in plants. In vitro and in vivo pull-down assays confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical microtubules were more sensitive to treatment with the microtubule-disrupting drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2-1, cortical microtubules were insensitive to oryzalin treatment. These results provide important insight into how BR regulates plant pavement cell and leaf growth by mediating the stabilization of microtubules by BIN2.

  18. Neurite outgrowth stimulatory effects of myco­synthesized AuNPs from Hericium erinaceus (Bull.: Fr. Pers. on pheochromocytoma (PC-12 cells

    Directory of Open Access Journals (Sweden)

    Raman J

    2015-09-01

    extension on PC-12 cells. Nerve growth factor 50 ng/mL was used as a positive control. Treatment with different concentrations (nanograms of AuNPs resulted in neuronal differentiation and neuronal elongation. AuNPs induced maximum neurite outgrowth of 13% at 600 ng/mL concentration. Conclusion: In this study, the AuNPs synthesis was achieved by a simple, low-cost, and rapid bioreduction approach. AuNPs were shown to have potential neuronal differentiation and stimulated neurite outgrowth. The water-soluble bioconstituents could be responsible for the neuroactivity. This is the first report for the biosynthesis of AuNPs using the hot aqueous extract of H. erinaceus. Keywords: AuNPs, nanoparticles, Hericium erinaceus, PC-12, neurite outgrowth

  19. Plant Growth Regulators as Potential Tools in Aquatic Plant Management: Efficacy and Persistence in Small-Scale Tests

    Science.gov (United States)

    1994-01-01

    gratefully acknowledge the support of the Waterways Experi- ment Station and Drs. Howard Westerdahl and Kurt Getsinger as this research was being conducted...E. Westerdahl , eds., Plant Growth Regulator Society of America, San Antonio, TX, 127-45. Anderson, L. W. J., and Dechoretz, N. (1988). "Bensulfuron...Vegetation Management. J. E. Kaufman and H. E. Westerdahl , eds., Plant Growth Regulator Society of America, San Antonio, TX, 155-86. Herbicide Handbook

  20. Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of a long bone?

    Science.gov (United States)

    Brouwers, J E M; van Donkelaar, C C; Sengers, B G; Huiskes, R

    2006-01-01

    Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.

  1. The effect of cutting origin and organic plant growth regulator on the growth of Daun Ungu (Graptophyllum pictum) through stem cutting method

    Science.gov (United States)

    Pratama, S. P.; Yunus, A.; Purwanto, E.; Widyastuti, Y.

    2018-03-01

    Graptophyllum pictum is one of medical plants which has important chemical content to treat diseases. Leaf, bark and flower can be used to facilitate menstruation, treat hemorrhoid, constipation, ulcers, ulcers, swelling, and earache. G. pictum is difficult to propagated by seedling due to the long duration of seed formation, thusvegetative propagation is done by stem cutting. The aims of this study are to obtain optimum combination of cutting origin and organic plant growth regulator in various consentration for the growth of Daun Ungu through stem cutting method. This research was conducted at Research center for Medicinal Plant and Traditional DrugTanjungsari, Tegal Gede, Karanganyar in June to August 2016. Origin of cuttings and organic plant growth regulator were used as treatments factor. A completely randomized design (RAL) is used and data were analyzed by F test (ANOVA) with a confidence level of 95%. Any significant differences among treatment followed with Duncan test at a = 5%. The research indicates that longest root was resulted from the treatment of 0,5 ml/l of organic plant growth regulator. The treatment of 1 ml/l is able to increase the fresh and dry weight of root, treatment of 1,5 ml/l of organic plant growth regulator was able to increase the percentage of growing shoots. Treatment of base part as origin of cuttings increases the length, fresh weight and and dry weight of shoot, increase the number of leaves. Interaction treatment between 1 ml/l consentration of organic plant growth regulator and central part origin of cuttings is capable of increasing the leaf area, whereas treatment without organic plant growth regulator and base part as planting material affects the smallest leaf area.

  2. Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

    Directory of Open Access Journals (Sweden)

    Hiroshi Nango

    2017-10-01

    Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

  3. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    International Nuclear Information System (INIS)

    Pizzurro, Daniella M.; Dao, Khoi; Costa, Lucio G.

    2014-01-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  4. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Pizzurro, Daniella M.; Dao, Khoi [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Costa, Lucio G. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Department of Neuroscience, University of Parma, Parma (Italy)

    2014-02-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  5. Response of morphological and physiological growth attributes to foliar application of plant growth regulators in gladiolus 'white prosperity'

    International Nuclear Information System (INIS)

    Sajjad, Y.; Jaskani, M. J.; Qasim, M.

    2014-01-01

    Gladiolus is very popular among ornamental bulbous plants mainly used as cut flower and greatly demanded in the world floral market. Production of inferior quality spikes is one of the major hurdles for their export. The research was conducted under Faisalabad conditions to evaluate the use of plant growth regulators in order to improve the vegetative, floral and physiological attributes. Gladiolus plants were sprayed thrice with different concentrations (0.1, 0.4, 0.7 and 1mM) of gibberellic acid, benzylaminopurine and salicylic acid at three leaf stage, five leaf stage and slipping stage. Foliar application of 1mM gibberellic acid increased the plant height (122.14cm), spike length (58.41cm), florets spike-1 (13.49), corm diameter (4.43cm), corm weight (25.34g) and total cormel weight (20.45g) compared to benzylaminopurine and salicylic acid. Gibberellic acid at 1mM concentration also increased the total chlorophyll content to 7.72mg/g, total carotenoids (1.61mg/g), total soluble sugars (3.68mg/g) followed by application of benzylaminopurine. Salicylic acid application at 1mM concentration decreased the number of days to flower (64.93) compared to 76.12 days in non treated plants. (author)

  6. Harzianolide, a novel plant growth regulator and systemic resistance elicitor from Trichoderma harzianum.

    Science.gov (United States)

    Cai, Feng; Yu, Guanghui; Wang, Ping; Wei, Zhong; Fu, Lin; Shen, Qirong; Chen, Wei

    2013-12-01

    A detailed understanding of the effect of natural products on plant growth and protection will underpin new product development for plant production. The isolation and characterization of a known secondary metabolite named harzianolide from Trichoderma harzianum strain SQR-T037 were described, and the bioactivity of the purified compound as well as the crude metabolite extract in plant growth promotion and systemic resistance induction was investigated in this study. The results showed that harzianolide significantly promoted tomato seedling growth by up to 2.5-fold (dry weight) at a concentration of 0.1 ppm compared with the control. The result of root scan suggested that Trichoderma secondary metabolites may influence the early stages of plant growth through better root development for the enhancement of root length and tips. Both of the purified harzianolide and crude metabolite extract increased the activity of some defense-related enzymes to response to oxidative stress. Examination of six defense-related gene expression by real-time reverse transcription-PCR analysis revealed that harzianolide induces the expression of genes involved in the salicylic acid (PR1 and GLU) and jasmonate/ethylene (JERF3) signaling pathways while crude metabolite extract inhibited some gene expression (CHI-II and PGIP) related to basal defense in tomato plants. Further experiment showed that a subsequent challenge of harzianolide-pretreated plants with the pathogen Sclerotinia sclerotiorum resulted in higher systemic resistance by the reduction of lesion size. These results indicate that secondary metabolites of Trichoderma spp., like harzianolide, may play a novel role in both plant growth regulation and plant defense responses. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Science.gov (United States)

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  8. The Effect of Plant Growth Regulators on Callus Induction and Regeneration of Amygdalus communis

    Directory of Open Access Journals (Sweden)

    Naimeh SHARIFMOGHADAM

    2011-08-01

    Full Text Available The Almond (Amygdalus communis is one of the most important and oldest commercial nut crops, belonging to the Rosaceae family. Almond has been used as base material in pharmaceutical, cosmetic, hygienically and food industry. Propagation by tissue culture technique is the most important one in woody plants. In the current research, in vitro optimization of tissue culture and mass production of almond was investigated. In this idea, explants of actively growing shoots were collected and sterilized, then transferred to MS medium with different concentrations and combinations of plant growth regulators. The experiment was done in completely randomized blocks design, with 7 treatment and 30 replications. After 4 weeks, calli induction, proliferation, shoot length and number of shoot per explants were measured. Results showed that the best medium for shoot initiation and proliferation was MS + 0.5 mg/l IAA (Indol-3-Acetic Acid + 1 mg/l BA (Benzyl Adenine. Autumn was the best season for collecting explants. The shoots were transferred to root induction medium with different concentrations of plant growth regulators. The best root induction medium was MS + 0.5 mg/l IBA (Indol Butyric Acid.

  9. Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

  10. Flow-Regulated Growth of Titanium Dioxide (TiO2 ) Nanotubes in Microfluidics.

    Science.gov (United States)

    Fan, Rong; Chen, Xinye; Wang, Zihao; Custer, David; Wan, Jiandi

    2017-08-01

    Electrochemical anodization of titanium (Ti) in a static, bulk condition is used widely to fabricate self-organized TiO 2 nanotube arrays. Such bulk approaches, however, require extended anodization times to obtain long TiO 2 nanotubes and produce only vertically aligned nanotubes. To date, it remains challenging to develop effective strategies to grow long TiO 2 nanotubes in a short period of time, and to control the nanotube orientation. Here, it is shown that the anodic growth of TiO 2 nanotubes is significantly enhanced (≈16-20 times faster) under flow conditions in microfluidics. Flow not only controls the diameter, length, and crystal orientations of TiO 2 nanotubes, but also regulates the spatial distribution of nanotubes inside microfluidic devices. Strikingly, when a Ti thin film is deposited on silicon substrates and anodized in microfluidics, both vertically and horizontally aligned (relative to the bottom substrate) TiO 2 nanotubes can be produced. The results demonstrate previously unidentified roles of flow in the regulation of growth of TiO 2 nanotubes, and provide powerful approaches to effectively grow long, oriented TiO 2 nanotubes, and construct hierarchical TiO 2 nanotube arrays on silicon-based materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Effect of growth regulators application on the quality maintenance of 'Brookfield' apples

    Directory of Open Access Journals (Sweden)

    Auri Brackmann

    2015-01-01

    Full Text Available AbstractThe main goal of the present study was to elucidate the effect of growth regulators at harvest and postharvest quality of 'Brookfield' apples stored under controlled atmosphere through a multivariate approach. Thus, an experiment with two steps (field and storage was carried out. The treatments in field were applied with an output of 1,000 L ha–1 of water. The following treatments were tested: Control: only water application; AVG (aminoethoxyvinylglycine: 0.83 kg ha–1 of Retain® applied 30 days before harvest (BH; NAA (naphthalene acetic acid: 40g ha–1of naphthalene acetic acid applied 7 days BH; Ethephon: 2.0 L ha–1 of Ethrel® applied 10 days BH; 1-MCP: 0.625µL L–1 of 1-MCP (1-methylcyclopropene: applied during postharvest (storage; LE (low ethylene: with the allocation of potassium permanganate sachets during postharvest. Fruits treated with AVG in the field showed an opposite response to the fruits with NAA. AVG application followed by another growth regulator (AVG + Ethephon and AVG + NAA showed an advance in maturation, nearing these fruits to the control treatment, this effect is likely related to the higher ethylene production by these fruits compared to fruits with AVG alone. AVG, 1-MCP and LE kept a similar response on quality maintenance. Ethephon application prevented the negative effect of NAA at harvest, but after storage, the combined NAA + ethephon application increased the physiological disorders, reducing internal quality.

  12. Transcriptional regulation of the protein kinase a subunits in Saccharomyces cerevisiae during fermentative growth.

    Science.gov (United States)

    Galello, Fiorella; Pautasso, Constanza; Reca, Sol; Cañonero, Luciana; Portela, Paula; Moreno, Silvia; Rossi, Silvia

    2017-12-01

    Yeast cells can adapt their growth in response to the nutritional environment. Glucose is the favourite carbon source of Saccharomyces cerevisiae, which prefers a fermentative metabolism despite the presence of oxygen. When glucose is consumed, the cell switches to the aerobic metabolism of ethanol, during the so-called diauxic shift. The difference between fermentative and aerobic growth is in part mediated by a regulatory mechanism called glucose repression. During glucose derepression a profound gene transcriptional reprogramming occurs and genes involved in the utilization of alternative carbon sources are expressed. Protein kinase A (PKA) controls different physiological responses following the increment of cAMP as a consequence of a particular stimulus. cAMP-PKA is one of the major pathways involved in the transduction of glucose signalling. In this work the regulation of the promoters of the PKA subunits during respiratory and fermentative metabolism are studied. It is demonstrated that all these promoters are upregulated in the presence of glycerol as carbon source through the Snf1/Cat8 pathway. However, in the presence of glucose as carbon source, the regulation of each PKA promoter subunits is different and only TPK1 is repressed by the complex Hxk2/Mig1 in the presence of active Snf1. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jingshan Zhao

    Full Text Available The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL, a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF signaling and angiogenesis in endothelial cells (ECs. We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.

  14. Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood.

    Science.gov (United States)

    Barroca, Vilma; Lewandowski, Daniel; Jaracz-Ros, Agnieszka; Hardouin, Sylvie-Nathalie

    2017-02-01

    Insulin-like Growth Factor 2 (IGF2) belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC) successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Effects of plant growth regulators on seed germination and callus induction of hylocereus costaricensis

    International Nuclear Information System (INIS)

    Sheng, W.K.

    2016-01-01

    Dragon fruit (Hylocereus costaricensis) belongs to the family Cactaceae and are climbing vines which have received worldwide attention in recent years. However, there are still lack of information on the protocols for the establishment of In vitro culture system. In the present study, seed germination percentage were determined by culturing seeds on semi-solid Murashige and Skoog medium (MS) supplemented with 1 ppm 6-Benzylaminopurine (BAP) together with either 0, 0.5 or 0.8 ppm of Indole-3-butyric acid (IBA). Germination percentage was the highest by using plant growth regulators (PGRs) combination of 1 ppm BAP and 0 ppm IBA (93.33%). Subsequently, the cotyledons from seedlings of the germinated seeds were used for subsequent callus induction. Small pieces of cotyledons were excised and cultured on MS medium fortified with 0.45, 0.9, 1.8, 2.7, 3.6, and 4.5 ppm of 2,4-Dichlorophenoxyacetic acid (2,4-D) together with either 0, 0.9 or 1.8 ppm of BAP. Callus induction percentage was highest using the plant growth regulators (PGRs) combination of 3.6 ppm 2,4-D and 1.8 ppm BAP (75%). Hence, 3.6 ppm of 2,4-D and 1.8 ppm BAP was the best combination for callus induction of Hylocereus costaricensis. (author)

  16. Paternal Insulin-like Growth Factor 2 (Igf2 Regulates Stem Cell Activity During Adulthood

    Directory of Open Access Journals (Sweden)

    Vilma Barroca

    2017-02-01

    Full Text Available Insulin-like Growth Factor 2 (IGF2 belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span.

  17. Money Laundering, Corruption and Growth: An Empirical Rationale for a Global Convergence on Anti-Money Laundering Regulation

    OpenAIRE

    Cavalcante Veiga, Luiz Humberto; Andrade, Joaquim Pinto

    2006-01-01

    This paper provides empirical evidence on the impact of anti-money laundering regulations on growth and, it examines the rationale for a global adoption of these rules. The empirical results have led us to confirm a positive relation between low corruption levels and high investment and growth. We approached the impact on growth of money laundering prevention (MLP) initiatives in two ways: first, by verifying that the existence of these initiatives affects the perception of corruption. Second...

  18. Nitric Oxide Regulates Seedling Growth and Mitochondrial Responses in Aged Oat Seeds

    Directory of Open Access Journals (Sweden)

    Chunli Mao

    2018-04-01

    Full Text Available Mitochondria are the source of reactive oxygen species (ROS in plant cells and play a central role in the mitochondrial electron transport chain (ETC and tricarboxylic acid cycle (TCA cycles; however, ROS production and regulation for seed germination, seedling growth, as well as mitochondrial responses to abiotic stress, are not clear. This study was conducted to obtain basic information on seed germination, embryo mitochondrial antioxidant responses, and protein profile changes in artificial aging in oat seeds (Avena sativa L. exposed to exogenous nitric oxide (NO treatment. The results showed that the accumulation of H2O2 in mitochondria increased significantly in aged seeds. Artificial aging can lead to a loss of seed vigor, which was shown by a decline in seed germination and the extension of mean germination time (MGT. Seedling growth was also inhibited. Some enzymes, including catalase (CAT, glutathione reductase (GR, dehydroascorbate reductase (DHAR, and monodehydroascorbate reductase (MDHAR, maintained a lower level in the ascorbate-glutathione (AsA-GSH scavenging system. Proteomic analysis revealed that the expression of some proteins related to the TCA cycle were down-regulated and several enzymes related to mitochondrial ETC were up-regulated. With the application of 0.05 mM NO in aged oat seeds, a protective effect was observed, demonstrated by an improvement in seed vigor and increased H2O2 scavenging ability in mitochondria. There were also higher activities of CAT, GR, MDHAR, and DHAR in the AsA-GSH scavenging system, enhanced TCA cycle-related enzymes (malate dehydrogenase, succinate-CoA ligase, fumarate hydratase, and activated alternative pathways, as the cytochrome pathway was inhibited. Therefore, our results indicated that seedling growth and seed germinability could retain a certain level in aged oat seeds, predominantly depending on the lower NO regulation of the TCA cycle and AsA-GSH. Thus, it could be concluded that the

  19. Histone Deacetylase HDA-2 Regulates Trichoderma atroviride Growth, Conidiation, Blue Light Perception, and Oxidative Stress Responses.

    Science.gov (United States)

    Osorio-Concepción, Macario; Cristóbal-Mondragón, Gema Rosa; Gutiérrez-Medina, Braulio; Casas-Flores, Sergio

    2017-02-01

    Fungal blue-light photoreceptors have been proposed as integrators of light and oxidative stress. However, additional elements participating in the integrative pathway remain to be identified. In Trichoderma atroviride, the blue-light regulator (BLR) proteins BLR-1 and -2 are known to regulate gene transcription, mycelial growth, and asexual development upon illumination, and recent global transcriptional analysis revealed that the histone deacetylase-encoding gene hda-2 is induced by light. Here, by assessing responses to stimuli in wild-type and Δhda-2 backgrounds, we evaluate the role of HDA-2 in the regulation of genes responsive to light and oxidative stress. Δhda-2 strains present reduced growth, misregulation of the con-1 gene, and absence of conidia in response to light and mechanical injury. We found that the expression of hda-2 is BLR-1 dependent and HDA-2 in turn is essential for the transcription of early and late light-responsive genes that include blr-1, indicating a regulatory feedback loop. When subjected to reactive oxygen species (ROS), Δhda-2 mutants display high sensitivity whereas Δblr strains exhibit the opposite phenotype. Consistently, in the presence of ROS, ROS-related genes show high transcription levels in wild-type and Δblr strains but misregulation in Δhda-2 mutants. Finally, chromatin immunoprecipitations of histone H3 acetylated at Lys9/Lys14 on cat-3 and gst-1 promoters display low accumulation of H3K9K14ac in Δblr and Δhda-2 strains, suggesting indirect regulation of ROS-related genes by HDA-2. Our results point to a mutual dependence between HDA-2 and BLR proteins and reveal the role of these proteins in an intricate gene regulation landscape in response to blue light and ROS. Trichoderma atroviride is a free-living fungus commonly found in soil or colonizing plant roots and is widely used as an agent in biocontrol as it parasitizes other fungi, stimulates plant growth, and induces the plant defense system. To survive in

  20. Tall or short? Slender or thick? A plant strategy for regulating elongation growth of roots by low concentrations of gibberellin.

    Science.gov (United States)

    Tanimoto, Eiichi

    2012-07-01

    Since the plant hormone gibberellin (GA) was discovered as a fungal toxin that caused abnormal elongation of rice shoots, the physiological function of GA has mainly been investigated in relation to the regulation of plant height. However, an indispensable role for GA in root growth has been elucidated by using severely GA-depleted plants, either with a gene mutation in GA biosynthesis or which have been treated by an inhibitor of GA biosynthesis. The molecular sequence of GA signalling has also been studied to understand GA functions in root growth. This review addresses research progress on the physiological functions of GA in root growth. Concentration-dependent stimulation of elongation growth by GA is important for the regulation of plant height and root length. Thus the endogenous level of GA and/or the GA sensitivity of shoots and roots plays a role in determining the shoot-to-root ratio of the plant body. Since the shoot-to-root ratio is an important parameter for agricultural production, control of GA production and GA sensitivity may provide a strategy for improving agricultural productivity. The sequence of GA signal transduction has recently been unveiled, and some component molecules are suggested as candidate in planta regulatory sites and as points for the artificial manipulation of GA-mediated growth control. This paper reviews: (1) the breakthrough dose-response experiments that show that root growth is regulated by GA in a lower concentration range than is required for shoot growth; (2) research on the regulation of GA biosynthesis pathways that are known predominantly to control shoot growth; and (3) recent research on GA signalling pathways, including GA receptors, which have been suggested to participate in GA-mediated growth regulation. This provides useful information to suggest a possible strategy for the selective control of shoot and root growth, and to explain how GA plays a role in rosette and liana plants with tall or short, and slender

  1. Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

    Directory of Open Access Journals (Sweden)

    Callihan Phillip

    2008-12-01

    Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

  2. Molecular regulation of aluminum resistance and sulfur nutrition during root growth.

    Science.gov (United States)

    Alarcón-Poblete, Edith; Inostroza-Blancheteau, Claudio; Alberdi, Miren; Rengel, Zed; Reyes-Díaz, Marjorie

    2018-01-01

    Aluminum toxicity and sulfate deprivation both regulate microRNA395 expression, repressing its low-affinity sulfate transporter ( SULTR2;1 ) target. Sulfate deprivation also induces the high-affinity sulfate transporter gene ( SULTR12 ), allowing enhanced sulfate uptake. Few studies about the relationships between sulfate, a plant nutrient, and aluminum, a toxic ion, are available; hence, the molecular and physiological processes underpinning this interaction are poorly understood. The Al-sulfate interaction occurs in acidic soils, whereby relatively high concentrations of trivalent toxic aluminum (Al 3+ ) may hamper root growth, limiting uptake of nutrients, including sulfur (S). On the other side, Al 3+ may be detoxified by complexation with sulfate in the acid soil solution as well as in the root-cell vacuoles. In this review, we focus on recent insights into the mechanisms governing plant responses to Al toxicity and its relationship with sulfur nutrition, emphasizing the role of phytohormones, microRNAs, and ion transporters in higher plants. It is known that Al 3+ disturbs gene expression and enzymes involved in biosynthesis of S-containing cysteine in root cells. On the other hand, Al 3+ may induce ethylene biosynthesis, enhance reactive oxygen species production, alter phytohormone transport, trigger root growth inhibition and promote sulfate uptake under S deficiency. MicroRNA395, regulated by both Al toxicity and sulfate deprivation, represses its low-affinity Sulfate Transporter 2;1 (SULTR2;1) target. In addition, sulfate deprivation induces High Affinity Sulfate Transporters (HAST; SULTR1;2), improving sulfate uptake from low-sulfate soil solutions. Identification of new microRNAs and cloning of their target genes are necessary for a better understanding of the role of molecular regulation of plant resistance to Al stress and sulfate deprivation.

  3. EFFECT OF SOME PLANT GROWTH REGULATORS WITH RETARDING ACTIVITY ON SPRING PEA FOR GRAIN

    Directory of Open Access Journals (Sweden)

    Tsenka ZHELYAZKOVA

    2012-12-01

    Full Text Available A field experiment was conducted at Trakia University - Stara Zagora to establish the effect of some growth retardants on morphological and productive parameters in spring pea for grain variety Bogatir. Three combined preparations: Trisalvit (phenylphthalamic acid + chlorocholine chloride + chlorophenoxyacetic acid +salicylic acid at doses of 300 and 400 сmз*ha-1; SM-21 (phenylphthalamic acid + chlorocholine chloride at doses of 300 and 400 сmз*ha-1 and PNSA-44 (phenylphthalamic acid + naphthaleneacetic acid + chlorophenoxyacetic acid at doses of 200 and 300 сmз*ha-1 were applied in the early growth phase of the plant up to a height of 15-20 cm. The study showed that the greatest reduction in the stem height (by 12.8% compared to untreated plants was achieved by applying SM-21 (400 сmз*ha-1. The application of growth regulators Trisalvit and SM-21 had no appreciable effect on the production of spring pea grain. Maximum values of yield structure components (number of pods and grain per plant, grain mass per plant and mass of 1000 grain and the yield were obtained after application of PNSA-44 (300 сmз*ha-1 - up to 5.6% (117.2 kg*ha-1 more grain than the control. The investigation of the influence of tested factors (retardant, dose and year demonstrated that the conditions of the year as a factor had the strongest effect on plant height and grain yield.

  4. Glycolysis is governed by growth regime and simple enzyme regulation in adherent MDCK cells.

    Science.gov (United States)

    Rehberg, Markus; Ritter, Joachim B; Reichl, Udo

    2014-10-01

    Due to its vital importance in the supply of cellular pathways with energy and precursors, glycolysis has been studied for several decades regarding its capacity and regulation. For a systems-level understanding of the Madin-Darby canine kidney (MDCK) cell metabolism, we couple a segregated cell growth model published earlier with a structured model of glycolysis, which is based on relatively simple kinetics for enzymatic reactions of glycolysis, to explain the pathway dynamics under various cultivation conditions. The structured model takes into account in vitro enzyme activities, and links glycolysis with pentose phosphate pathway and glycogenesis. Using a single parameterization, metabolite pool dynamics during cell cultivation, glucose limitation and glucose pulse experiments can be consistently reproduced by considering the cultivation history of the cells. Growth phase-dependent glucose uptake together with cell-specific volume changes generate high intracellular metabolite pools and flux rates to satisfy the cellular demand during growth. Under glucose limitation, the coordinated control of glycolytic enzymes re-adjusts the glycolytic flux to prevent the depletion of glycolytic intermediates. Finally, the model's predictive power supports the design of more efficient bioprocesses.

  5. A local maximum in gibberellin levels regulates maize leaf growth by spatial control of cell division.

    Science.gov (United States)

    Nelissen, Hilde; Rymen, Bart; Jikumaru, Yusuke; Demuynck, Kirin; Van Lijsebettens, Mieke; Kamiya, Yuji; Inzé, Dirk; Beemster, Gerrit T S

    2012-07-10

    Plant growth rate is largely determined by the transition between the successive phases of cell division and expansion. A key role for hormone signaling in determining this transition was inferred from genetic approaches and transcriptome analysis in the Arabidopsis root tip. We used the developmental gradient at the maize leaf base as a model to study this transition, because it allows a direct comparison between endogenous hormone concentrations and the transitions between dividing, expanding, and mature tissue. Concentrations of auxin and cytokinins are highest in dividing tissues, whereas bioactive gibberellins (GAs) show a peak at the transition zone between the division and expansion zone. Combined metabolic and transcriptomic profiling revealed that this GA maximum is established by GA biosynthesis in the division zone (DZ) and active GA catabolism at the onset of the expansion zone. Mutants defective in GA synthesis and signaling, and transgenic plants overproducing GAs, demonstrate that altering GA levels specifically affects the size of the DZ, resulting in proportional changes in organ growth rates. This work thereby provides a novel molecular mechanism for the regulation of the transition from cell division to expansion that controls organ growth and size. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Kimberly R Hagel

    Full Text Available Calcium is a primary second messenger in all cells that functions in processes ranging from cellular proliferation to synaptic transmission. Proper regulation of calcium is achieved through numerous mechanisms involving channels, sensors, and buffers notably containing one or more EF-hand calcium binding domains. The Drosophila genome encodes only a single 6 EF-hand domain containing protein, Cbp53E, which is likely the prototypic member of a small family of related mammalian proteins that act as calcium buffers and calcium sensors. Like the mammalian homologs, Cbp53E is broadly though discretely expressed throughout the nervous system. Despite the importance of calcium in neuronal function and growth, nothing is known about Cbp53E's function in neuronal development. To address this deficiency, we generated novel null alleles of Drosophila Cbp53E and examined neuronal development at the well-characterized larval neuromuscular junction. Loss of Cbp53E resulted in increases in axonal branching at both peptidergic and glutamatergic neuronal terminals. This overgrowth could be completely rescued by expression of exogenous Cbp53E. Overexpression of Cbp53E, however, only affected the growth of peptidergic neuronal processes. These findings indicate that Cbp53E plays a significant role in neuronal growth and suggest that it may function in both local synaptic and global cellular mechanisms.

  7. Polycomb Group Protein PHF1 Regulates p53-dependent Cell Growth Arrest and Apoptosis*

    Science.gov (United States)

    Yang, Yang; Wang, Chenji; Zhang, Pingzhao; Gao, Kun; Wang, Dejie; Yu, Hongxiu; Zhang, Ting; Jiang, Sirui; Hexige, Saiyin; Hong, Zehui; Yasui, Akira; Liu, Jun O.; Huang, Haojie; Yu, Long

    2013-01-01

    Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression. PMID:23150668

  8. TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

    Science.gov (United States)

    Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

    2011-01-01

    We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

  9. Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

    Directory of Open Access Journals (Sweden)

    Darci M Fink

    Full Text Available The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery.

  10. Interaction of plant growth regulators and reactive oxygen species to regulate petal senescence in wallflowers (Erysimum linifolium).

    Science.gov (United States)

    Salleh, Faezah Mohd; Mariotti, Lorenzo; Spadafora, Natasha D; Price, Anna M; Picciarelli, Piero; Wagstaff, Carol; Lombardi, Lara; Rogers, Hilary

    2016-04-02

    transcript abundance of WPS46, an auxin-induced gene. A model for the interaction between cytokinins, ethylene, reactive oxygen species and auxin in the regulation of floral senescence in wallflowers is proposed. The combined increase in ethylene and reduction in cytokinin triggers the initiation of senescence and these two plant growth regulators directly or indirectly result in increased reactive oxygen species levels. A fall in conjugated auxin and/or the total auxin pool eventually triggers abscission.

  11. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    Energy Technology Data Exchange (ETDEWEB)

    Flaskos, J., E-mail: flaskos@vet.auth.gr [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Nikolaidis, E. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Harris, W. [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Sachana, M. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Hargreaves, A.J., E-mail: alan.hargreaves@ntu.ac.uk [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2011-11-15

    Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43

  12. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    International Nuclear Information System (INIS)

    Flaskos, J.; Nikolaidis, E.; Harris, W.; Sachana, M.; Hargreaves, A.J.

    2011-01-01

    Previous work in our laboratory has shown that sub-lethal concentrations (1–10 μM) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1–10 μM) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: ► Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells ► Acetylcholinesterase exhibits sustained inhibition throughout exposure ► The levels of neurofilament heavy chain and GAP-43 protein are reduced ► Neurofilament heavy chain forms aggregates in cell

  13. The Fat-Dachsous signaling pathway regulates growth of horns in Trypoxylus dichotomus, but does not affect horn allometry.

    Science.gov (United States)

    Hust, James; Lavine, Mark D; Worthington, Amy M; Zinna, Robert; Gotoh, Hiroki; Niimi, T; Lavine, Laura

    Males of the Asian rhinoceros beetle, Trypoxylus dichotomus, possess exaggerated head and thoracic horns that scale dramatically out of proportion to body size. While studies of insulin signaling suggest that this pathway regulates nutrition-dependent growth including exaggerated horns, what regulates disproportionate growth has yet to be identified. The Fat signaling pathway is a potential candidate for regulating disproportionate growth of sexually-selected traits, a hypothesis we advanced in a previous paper (Gotoh et al., 2015). To investigate the role of Fat signaling in the growth and scaling of the sexually dimorphic, condition-dependent traits of the in the Asian rhinoceros beetle T. dichotomus, we used RNA interference to knock down expression of fat and its co-receptor dachsous. Knockdown of fat, and to a lesser degree dachsous, caused shortening and widening of appendages, including the head and thoracic horns. However, scaling of horns to body size was not affected. Our results show that Fat signaling regulates horn growth in T. dichotomus as it does in appendage growth in other insects. However, we provide evidence that Fat signaling does not mediate the disproportionate, positive allometric growth of horns in T. dichotomus. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. IGFBP-4 regulates adult skeletal growth in a sex-specific manner.

    Science.gov (United States)

    Maridas, David E; DeMambro, Victoria E; Le, Phuong T; Nagano, Kenichi; Baron, Roland; Mohan, Subburaman; Rosen, Clifford J

    2017-04-01

    Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old Igfbp4 -/- mice. Both male and female adult Igfbp4 -/- mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old Igfbp4 -/- females, but not in males. Femoral trabecular BV/TV and thickness, cortical fraction and thickness in 16-week-old Igfbp4 -/- females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in Igfbp4 -/- females. In contrast, Igfbp4 -/- males had lower mineralized surface/bone surface. Femoral expression of Sost and circulating levels of sclerostin were reduced but only in Igfbp4 -/- males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from Igfbp4 -/- females but decreased in males. In sum, our results indicate that loss of Igfbp4 affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor. © 2017 The authors.

  15. The Effects of Plant Growth Regulators on Cell Growth, Protein, Carotenoid, PUFAs and Lipid Production of Chlorella pyrenoidosa ZF Strain

    Directory of Open Access Journals (Sweden)

    Huanmin Du

    2017-10-01

    Full Text Available In the present study, eight kinds plant growth regulators—salicylic acid (SA, 1-naphthaleneacetic acid (NAA, gibberellic acid (GA3, 6-benzylaminopurine (6-BA, 2, 4-epi-brassinolide (EBR, abscisic acid (ABA, ethephon (ETH, and spermidine (SPD—were used to investigate the impact on microalgal biomass, lipid, total soluble protein, carotenoids, and polyunsaturated fatty acids (PUFAS production of Chlorella pyrenoidosa ZF strain. The results showed the quickest biomass enhancement was induced by 50 mg·L−1 NAA, with a 6.3-fold increase over the control; the highest protein content was increased by 0.005 mg·L−1 ETH, which produced 3.5-fold over the control; total carotenoids content was induced most effectively by 1 mg·L−1 NAA with 3.6-fold higher production than the control; the most efficient elicitor for lipid production was 5 mg·L−1 GA3 at 1.9-fold of the control; 0.2 mg·L−1 ETH induced the abundant production of 1.82 ± 0.23% linoleic acid; 0.65 ± 0.01% linolenic acid was induced by 1 mg·L−1 NAA; 2.53 ± 0.15% arachidonic acid and 0.44 ± 0.05% docosahexaenoic acid were induced by 5 mg·L−1 GA3. Transcriptional expression levels of seven lipid-related genes, including ACP, BC, FAD, FATA, KAS, MCTK, and SAD, were studied by real-time RT-q-PCR. 5 mg·L−1 GA3 was the most effective regulator for transcriptional expressions of these seven genes, producing 23-fold ACP, 31-fold BC, 25-fold FAD, 6-fold KAS, 12-fold MCTK compared with the controls, respectively.

  16. Exogenous applications of plant growth regulators influence the reproductive growth of citrus sinensis osbeck cv. blood red

    International Nuclear Information System (INIS)

    Khan, A.S.; Malik, A.U.; Ahmad, S.; Ahmad, I.

    2014-01-01

    To study the influence of exogenous applications of plant growth regulators on the reproductive behaviour of low bearing sweet orange (Citrus sinensis Osbeck) trees, three separate experiments were conducted on twelve years old 'Blood Red' Sweet orange trees budded on Rough Lemon (Citrus jambheri L.) root stock. In the first experiment, trees were sprayed with 20 mg L-1 2, 4-D and GA3 alone or in combination at mid bloom (MB) stage, whilst in the second and third experiments 20 mg L-1 2, 4-D and GA3 alone or in combination were sprayed at MB + 6 weeks after MB, and at MB + 22 and 28 weeks after MB stages, respectively. A single tree was selected as an experimental unit and each treatment was replicated four times. Data regarding the flowering intensity, flower drop, fruit set, fruit drop and fruit harvest percentages (%) were collected and analyzed statistically. In all experiments exogenous application of 20 mg L-1 2, 4-D and GA3 alone or in combination to Blood Red sweet orange trees reduced the flower drop % and increased the fruit set % as compared to untreated trees. Application 2, 4-D and GA3 alone or in combination at MB did not affect the fruit drop % and fruit harvest % in contrast to untreated trees. The trees sprayed with 20 mg L-1 GA3 alone or in combination with 2, 4-D at MB + 22 and 28 weeks after MB exhibited highest reduction in the fruit drop % compared to control trees. In conclusions application GA3 (20 mg L-1) alone or in combination of 2, 4-D (20 mg L-1) at MB + 22 and 28 weeks after MB can be used effectively to increase the fruit set and reduce the fruit drop in Blood Red sweet oranges. (author)

  17. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    Science.gov (United States)

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  18. Plant growth regulators ameliorate or exacerbate abiotic and biotic stress effects on Zea mays kernel weight in a genotype-specific manner

    OpenAIRE

    Wang, Yishi; Stutts, Lauren; Stapleton, Ann

    2016-01-01

    Plant growth regulators have documented roles in plant responses to single stresses. In combined-stress environments, plants display novel genetic architecture for growth traits and the response to growth regulators is unclear. We investigated the role of plant growth regulators in combined-stress responses in Zea mays. Twelve maize inbreds were exposed to all combinations of the following stressors: drought, nitrogen, and density stress. Chemical treatments were utilized to alter balances of...

  19. The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.

    Science.gov (United States)

    Ashcroft, M; Stephens, R M; Hallberg, B; Downward, J; Kaplan, D R

    1999-08-12

    The Trk/Nerve Growth Factor receptor mediates the rapid activation of a number of intracellular signaling proteins, including phosphatidylinositol 3-kinase (PI 3-kinase). Here, we describe a novel, NGF-inducible system that we used to specifically address the signaling potential of endogenous PI 3-kinase in NGF-mediated neuronal survival and differentiation processes. This system utilizes a Trk receptor mutant (Trk(def)) lacking sequences Y490, Y785 and KFG important for the activation of the major Trk targets; SHC, PLC-gammal, Ras, PI 3-kinase and SNT. Trk(def) was kinase active but defective for NGF-induced responses when stably expressed in PC12nnr5 cells (which lack detectable levels of TrkA and are non-responsive to NGF). The PI 3-kinase consensus binding site, YxxM (YVPM), was introduced into the insert region within the kinase domain of Trk(def). NGF-stimulated tyrosine phosphorylation of the Trk(def)+PI 3-kinase addback receptor, resulted in the direct association and selective activation of PI 3-kinase in vitro and the production of PI(3,4)P2 and PI(3,4,5)P3 in vivo (comparable to wild-type). PC12nnr5 cells stably expressing Trk(def) + PI 3-kinase, initiated neurite outgrowth but failed to stably extend and maintain these neurites in response to NGF as compared to PC12 parental cells, or PC12nnr5 cells overexpressing wild-type Trk. However, Trk(def) + PI 3-kinase was fully competent in mediating NGF-induced survival processes. We propose that while endogenous PI 3-kinase can contribute in part to neurite initiation processes, its selective activation and subsequent signaling to downstream effectors such as Akt, functions mainly to promote cell survival in the PC12 system.

  20. The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB

    Directory of Open Access Journals (Sweden)

    Kaori Kubota

    2017-11-01

    Full Text Available Hachimijiogan (HJG is a traditional herbal medicine that improves anxiety disorders in patients with dementia. In this study, we tested the hypothesis that HJG exerts neurotrophic factor-like effects to ameliorate memory impairment in Alzheimer disease (AD model rats. First, we describe that HJG acts to induce neurite outgrowth in PC12 cells (a rat pheochromocytoma cell line like nerve growth factor (NGF in a concentration-dependent manner (3 μg/ml HJG, p < 0.05; 10–500 μg/ml HJG, p < 0.001. While six herbal constituents of HJG, Rehmannia root, Dioscorea rhizome, Rhizoma Alismatis, Poria sclerotium, Moutan bark, and Cinnamon bark, could induce neurite outgrowth effects, the effect was strongest with HJG (500 μg/ml. Second, we demonstrated that HJG-induced neurite outgrowth was blocked by an inhibitor of cAMP response element binding protein (CREB, KG-501 (10 μM, p < 0.001. Moreover, HJG was observed to induce CREB phosphorylation 20–90 min after treatment (20 min, 2.50 ± 0.58-fold and CRE-mediated transcription in cultured PC12 cells (500 μg/ml, p < 0.01; 1000 μg/ml, p < 0.001. These results suggest a CREB-dependent mechanism underlies the neurotrophic effects of HJG. Finally, we examined improvements of memory impairment following HJG treatment using a Morris water maze in AD model animals (CI + Aβ rats. Repeated oral administration of HJG improved memory impairment (300 mg/kg, p < 0.05; 1000 mg/kg, p < 0.001 and induced CREB phosphorylation within the hippocampus (1000 mg/kg, p < 0.01. Together, our results suggest that HJG possesses neurotrophic effects similar to those of NGF, and can ameliorate cognitive dysfunction in a rat dementia model via CREB activation. Thus, HJG could potentially be a substitute for neurotrophic factors as a treatment for dementia.

  1. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li Fan

    2010-04-01

    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  2. Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells.

    Science.gov (United States)

    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2017-03-15

    The PAC 1 receptor and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 activity by the PAC 1 receptor in retinoic acid-induced differentiating N2a neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. TG2 phosphorylation was monitored via immunoprecipitation and Western blotting. The role of TG2 in PAC 1 receptor-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with pituitary adenylate cyclase-activating polypeptide-27 (PACAP-27). PACAP-27 mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON and R283 and by pharmacological inhibition of protein kinase A (KT 5720 and Rp-cAMPs), protein kinase C (Ro 31-8220), MEK1/2 (PD 98059), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated PACAP-27 induced in situ TG2 activity. TG2 inhibition blocked PACAP-27 induced attenuation of hypoxia-induced cell death and outgrowth of axon-like processes. TG2 activation and cytoprotection were also observed in human SH-SY5Y cells. Together, these results demonstrate that TG2 activity was stimulated downstream of the PAC 1 receptor via a multi protein kinase dependent pathway. Furthermore, PAC 1 receptor-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results highlight the importance of TG2 in the cellular functions of the PAC 1 receptor. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Allelic deletions of cell growth regulators during progression of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, H; von der Maase, H; Christensen, M

    2000-01-01

    Cell growth regulators include proteins of the p53 pathway encoded by the genes CDKN2A (p16, p14arf), MDM2, TP53, and CDKN1A (p21) as well as proteins encoded by genes like RB1, E2F, and MYCL. In the present study we investigated allelic deletions of all these genes in each recurrent bladder tumor...... difference in the numbers of gene loci hit by deletions muscle-invasive versus noninvasive tumors (P = 0.0000002), with the genes most often hit by deletions in muscle-invasive tumors being TP53, RB1, and MYCL. A number of novel findings were made. Losses of MYCL and RB1 alleles were more pronounced...... that a characteristic difference between recurrent noninvasive and recurrent progressing bladder tumors is loss of cell cycle-regulatory genes in the latter group....

  4. Alteration in antioxidant potential of spinacia oleracea in response to selected plant growth regulators

    International Nuclear Information System (INIS)

    Aslam, M.; Sultana, B.; Ali, S.; Rehman, K.U.

    2013-01-01

    The spinach (Spinacia oleracea) plants treated with certain seed priming (bio-fertilizer and Humic acid) and foliar treatments (Humic acid, Moringa leaf extract, 6-Benzyl amino purine etc.) were tested for total phenolic content and the antioxidant activity. Methanolic extracts of all spinach samples were assessed performing three different protocols including Folin-Ciocalteu, reducing power and DPPH radical scavenging assays. TPC value ranged 4.678-13.236 mg GAE/g of dry matter. Reducing power assay showed values (absorbance at lambda max=700nm) in the range of 0.351-1.874 at 10 mg/mL extract concentration. The range of IC 50 values in DPPH radical scavenging assay was 0.499-1.063 mu g/mL extract concentration. The one way ANOVA under CRD showed significant differences among treatments. Among various plant growth regulators, fresh Moringa leaf extract proved as the potent enhancer of antioxidant activity of spinach leaves. (author)

  5. Monoclonal antibodies for the detection and quantitation of the endogenous plant growth regulator, abscisic acid

    Energy Technology Data Exchange (ETDEWEB)

    Mertens, R.; Weiler, E.W. (Bochum Univ. (Germany, F.R.). Lehrstuhl fuer Pflanzenphysiologie); Deus-Neumann, B. (Muenchen Univ. (Germany, F.R.). Inst. fuer pharmazeutische Biologie)

    1983-08-22

    Monoclonal antibodies (mAB) have been produced which recognize the physiologically active 2-cis-(S)-form of the endogenous plant growth regulator, abscisic acid (ABA). Cross-reaction with the ABA-catabolites, phaseic and dihydrophaseic acid, is negligible, and (R)-ABA, 2-trans-ABA, the ABA-conjugate, ABA-..beta..-D-glucopyranosyl ester, as well as the putative ABA precursor, xanthoxin, are totally unreactive. In addition to being very specific, the mAB exhibit high affinities for 2-cis-(S)-ABA; the K values were 7.9 x 10/sup 9/ l/mol and 3.7 x 10/sup 9/ l/mol for antibodies from two different clones. By mAB-radioimmunoassay (RIA), 4 pg of 2-cis-(S)-ABA (99.5% confidence level) can be detected. mAB-RIA can be used to quantitate ABA directly in unprocessed plant extracts.

  6. Monoclonal antibodies for the detection and quantitation of the endogenous plant growth regulator, abscisic acid

    International Nuclear Information System (INIS)

    Mertens, R.; Weiler, E.W.; Deus-Neumann, B.

    1983-01-01

    Monoclonal antibodies (mAB) have been produced which recognize the physiologically active 2-cis-(S)-form of the endogenous plant growth regulator, abscisic acid (ABA). Cross-reaction with the ABA-catabolites, phaseic and dihydrophaseic acid, is negligible, and (R)-ABA, 2-trans-ABA, the ABA-conjugate, ABA-β-D-glucopyranosyl ester, as well as the putative ABA precursor, xanthoxin, are totally unreactive. In addition to being very specific, the mAB exhibit high affinities for 2-cis-(S)-ABA; the K values were 7.9 x 10 9 l/mol and 3.7 x 10 9 l/mol for antibodies from two different clones. By mAB-radioimmunoassay (RIA), 4 pg of 2-cis-(S)-ABA (99.5% confidence level) can be detected. mAB-RIA can be used to quantitate ABA directly in unprocessed plant extracts. (Auth.)

  7. New Trend in Crop Production – Application of Plant Natural Multicomponent Growth Regulators with Bioprotective Effect

    Directory of Open Access Journals (Sweden)

    S.P. Ponomarenko

    2013-09-01

    Full Text Available With the help of the Dot-blot hybridization the difference in steps of homology between mRNA of control plants and small regulatory si/mi RNA isolated from second-generation plantlets of wheat, corn, soybeans, sugar beets, chickpea, etc. cultivated from the seeds of plants infected and processed by new polycomponent plant growth regulators Regoplant® and Stimpo® in the first generation was found. It is proved that this difference is related to a partial reprogramming of the cell genome under the influence of biostimulators on growing plants with infected backgrounds that turns out in induction of low-molecular si/miRNA with antipathogenic and antiparasitic properties, which are the components of the immune system of a living organism.

  8. Sensitivity of root-knot nematodes to gamma irradiation, salinity and plant growth regulator, cycocel

    Energy Technology Data Exchange (ETDEWEB)

    Sweelam, M E [Econ. Entomology Dept., Fac. Agric. Menoufia University Shebin El-Kom, (Egypt)

    1995-10-01

    The experiment was carried out at the experimental station of the faculty of agriculture, Menoufia Univ. To determine the sensitivity of root-knot nematode, Meloidogyne Javanica infecting tomato plants exposed to different doses of gamma irradiation 0,20,40,60,80 Gy, salinity levels 0. 1000, 2000, 4000 ppm and the plant growth regulator cycocel 0,200 ppm. Treated seeds were planted clay pots and salinity levels and cycocel concentrations were applied. Fresh weights and nematode populations were computed 3 months after application. Results indicated that 20 Gy, 1000 ppm salinity and cycocel gave the highest fresh weight of shoots and roots. The developmental stages and egg-laying females of nematode decreased by the increasing of irradiation dose and salinity levels. Root-knot galls decreased with 40 and 60 Gy, while significant increase was observed with 0 and 80 Gy, salinity levels decreased root galls. Cycocel decreased nematode population, egg-lying females and root-knot galls.

  9. Growth regulator induced mobilization of 14C-metabolites into sunflower heads

    International Nuclear Information System (INIS)

    Prasad, T.G.; Udaykumar, M.; Rama Rao, S.; Krishna Sastry, K.S.

    1977-01-01

    Effect of exogenous application of mixtures of NAA, Ga and BA to the head in sunflower, after pollination and fertilization, on the mobilization of 14 C-metabolites was studied. Application of such mixtures increased mobilization and altered the pattern of translocation. TIBA applied to the head when the ray florets only had commenced opening also caused an increase in mobilization of 14 C-metabolites. Percent activity in relation to the activity fixed by the leaf increased from 36.8 in control to 63 in TIBA treated head. Field experiments conducted for 2 seasons also confirmed effectiveness of TIBA application in increasing percent seed filling and also 1000 grain weight. In sunflower it was possible to increase the sink capacity by application of growth regulators. (author)

  10. Sensitivity of root-knot nematodes to gamma irradiation, salinity and plant growth regulator, cycocel

    International Nuclear Information System (INIS)

    Sweelam, M.E.

    1995-01-01

    The experiment was carried out at the experimental station of the faculty of agriculture, Menoufia Univ. To determine the sensitivity of root-knot nematode, Meloidogyne Javanica infecting tomato plants exposed to different doses of gamma irradiation 0,20,40,60,80 Gy, salinity levels 0. 1000, 2000, 4000 ppm and the plant growth regulator cycocel 0,200 ppm. Treated seeds were planted clay pots and salinity levels and cycocel concentrations were applied. Fresh weights and nematode populations were computed 3 months after application. Results indicated that 20 Gy, 1000 ppm salinity and cycocel gave the highest fresh weight of shoots and roots. The developmental stages and egg-laying females of nematode decreased by the increasing of irradiation dose and salinity levels. Root-knot galls decreased with 40 and 60 Gy, while significant increase was observed with 0 and 80 Gy, salinity levels decreased root galls. Cycocel decreased nematode population, egg-lying females and root-knot galls

  11. Effect of explant origin and different growth regulators on micropropagation of Pistacia atlantica ssp. mutica

    Directory of Open Access Journals (Sweden)

    Ali-Ashraf Mehrabi

    2015-06-01

    Full Text Available Propagation of wild pistachio as a multipurpose woody species is a hard and tedious task. In this research, an effective in vitro protocol was developed for rapid proliferation of wild pistachio (Pistacia atlantica ssp. mutica in MS medium supplemented with B5 vitamins and different growth regulators. Rooting of plantlets was tested by two treatments containing Rhizopon and IBA in ex vitro. With respect to the results, the nodal segments explants, produced the highest shoot frequency, leaf frequency and the tallest shoots. On the other hand, the tallest shoots were generated from shoot tip explant and medium containing of TDZ plus IAA. Both treatments (Rhizopon and IBA led to a remarkable increase in the number of roots, root length and rooting percentage compared to the control. These results may be applied for rapid proliferation to spread the pistachio trees and shrubs that are difficult and time consuming.

  12. Regulation of caspase-3 expression to maintain fetal growth in Porphyromonas gingivalis-infected pregnant rats

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2016-04-01

    Full Text Available Periodontal disease has been involved in a variety of systemic disorders and suspected as a potential risk factor for fetal growth restriction. Periodontal pathogenic bacteria may actively regulate embryonic development, implantation and placental trophoblast cell invasion. This study aimed to analyze the role of TNF-α, IL-10 and caspase-3 to maintain fetal growth in Porphyromonasgingivalis-infected pregnant rats. Female rats were infected with live-Porphyromonas gingivalis at concentration of 2x109 cells/ml into subgingival sulcus area of the maxillary first molar before and during pregnancy. They were sacrificed on gestational day (GD-14 and GD20. The weight and length of placentas and fetuses were evaluated. The expression of TNF-α, IL-10 and caspase-3 in macrophages and trophoblast cells were detected by immunohistochemistry. On GD14, TNF-α (R2=0.416;P=0.000 and IL-10 (R2=0.187;P=0.012 had an important role to increase expression of caspase-3 in the placenta, but only TNF-α (R2=0.393;P=0.000 was able to increase the expression of caspase-3 on GD20. TNF-α and caspase-3 also had an important role (P0.000. The increasing expressions of TNF-α and IL-10 did not only enhance immune protection, but also maintained the trophoblast cells survival by regulating expression of caspase-3. Porphyromonas gingivalis infection in maternal periodontal tissue can lead to decrease in placental weight, fetal weight and fetal length which mediated by increasing expression of TNF-α, IL-10 and caspase-3 in the placenta.

  13. Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury.

    Science.gov (United States)

    Ozturk, Anil Murat; Sozbilen, Murat Celal; Sevgili, Elvin; Dagci, Taner; Özyalcin, Halit; Armagan, Guliz

    2018-03-22

    Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI. Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex. In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Susceptibility of Ceraeochrysa cubana larvae and adults to six insect growth-regulator insecticides.

    Science.gov (United States)

    Ono, Éric Kodi; Zanardi, Odimar Zanuzo; Aguiar Santos, Kenia Fernanda; Yamamoto, Pedro Takao

    2017-02-01

    The impacts of six insect growth-regulators were assessed on the predator Ceraeochrysa cubana (Hagen) larvae and adults. Our results showed that diflubenzuron, lufenuron and pyriproxyfen caused 100% larva mortality, whereas buprofezin, methoxyfenozide and tebufenozide were similar to control treatment. In comparison to the control, buprofezin prolonged the duration of larval stage, while methoxyfenozide and tebufenozide reduced the predator larva development time. Buprofezin, methoxyfenozide and tebufenozide did not affect the C. cubana duration and survival of pupal stage, fecundity and fertility. However, methoxyfenozide and tebufenozide reduced predator female and male longevities. Based on a reduction coefficient, diflubenzuron, lufenuron and pyriproxyfen were highly harmful to first instar larvae, while buprofezin, methoxyfenozide and tebufenozide were considered slightly harmful to the predator. Estimating the life table parameters, our results showed that buprofezin, methoxyfenozide and tebufenozide reduced the C. cubana R o , r and λ. In comparison to the control, buprofezin prolonged the T and methoxyfenozide and tebufenozide shortened the predator T. In adults, our results showed that the insecticides did not cause significant mortality, but diflubenzuron, lufenuron and pyriproxyfen reduced the C. cubana fecundity and longevity. Diflubenzuron and lufenuron also reduced the C. cubana fertility. Based on a reduction coefficient, diflubenzuron and lufenuron were highly harmful to C. cubana adults, while pyriproxyfen was slightly harmful and buprofezin, methoxyfenozide and tebufenozide were considered harmless to the predator. Therefore, insect growth-regulators affect the C. cubana biological or populational parameters, and they can harm the integrated pest management programs that aim the predator conservation and/or augmentation in agroecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Growth regulators in reducing the size of orchid Fire-of-Star for commercialization in vase

    Directory of Open Access Journals (Sweden)

    Patricia Reiners Carvalho

    2016-05-01

    Full Text Available Fire-of-star (Epidendrum radicans Pav. ex Lindl. is a terrestrial orchid, native to Brazil, tussocks with leafy stems, always with many adventitious roots, releasing its long inflorescence with about 1.0 m from the apex of the stem, showing great potential in floriculture, but long flowering stem complicates their marketing vase. The objective of this study was to evaluate the effect of paclobutrazol (PBZ and mepiquat chloride (CLM the reduction of the size of the orchid E. radicans. Plants with an average height of 15 cm were cultivated in a greenhouse with 50% shading. The growth regulators used were PBZ at doses of 0; 5; 10; 15 and 20 mg L-1, and the CLM at doses of 0; 1; 2; 3; 4 and 5 mg L-1. The frequency of application was fortnightly, totaling ten applications. The experiment was installed on a randomized complete blocks, one block to the PBZ with 5 treatments and 10 replications and another block to the CLM, with 6 treatments and 10 replications. Data were submitted to analysis of variance at 5% probability and significance when seen performed regression analysis. The variables evaluated were number shoots, plant height (cm, number of flower stems and leaf area. The results indicated that E. radicans treated with 5 mg L-1 PBZ were 50% lower in height than the control plants. When CLM treated with a dose of 1 mg L-1 plants were 25% lower in height than the control plants, maintaining its aesthetic characteristics suitable for marketing in vases. Growth regulators in the applied doses did not affect the number of shoots and flower stems. PBZ treated plants had 50% of their leaf area compared to control while those treated with CLM doses remained with the same average leaf area of control.

  16. Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

    Science.gov (United States)

    Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

    2017-11-15

    Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to

  17. Fibroblast growth factor 21 has no direct role in regulating fertility in female mice

    Directory of Open Access Journals (Sweden)

    Garima Singhal

    2016-08-01

    Full Text Available Objective: Reproduction is an energetically expensive process. Insufficient calorie reserves, signaled to the brain through peripheral signals such as leptin, suppress fertility. Recently, fibroblast growth factor 21 (FGF21 was implicated as a signal from the liver to the hypothalamus that directly inhibits the hypothalamic–gonadotropin axis during fasting and starvation. However, FGF21 itself increases metabolic rate and can induce weight loss, which suggests that the effects of FGF21 on fertility may not be direct and may reflect changes in energy balance. Methods: To address this important question, we evaluated fertility in several mouse models with elevated FGF21 levels including ketogenic diet fed mice, fasted mice, mice treated with exogenous FGF21 and transgenic mice over-expressing FGF21. Results: We find that ketogenic diet fed mice remain fertile despite significant elevation in serum FGF21 levels. Absence of FGF21 does not alter transient infertility induced by fasting. Centrally infused FGF21 does not suppress fertility despite its efficacy in inducing browning of inguinal white adipose tissue. Furthermore, a high fat diet (HFD can restore fertility of female FGF21-overexpressing mice, a model of growth restriction, even in the presence of supraphysiological serum FGF21 levels. Conclusions: We conclude that FGF21 is not a direct physiological regulator of fertility in mice. The infertility observed in FGF21 overexpressing mice is likely driven by the increased energy expenditure and consequent excess calorie requirements resulting from high FGF21 levels. Keywords: FGF21, Fertility, Leptin, Hypothalamic action

  18. Effect of growth regulators in meristem culture of potato (solanum tuberosmum l.)

    International Nuclear Information System (INIS)

    Batool, A.; Zaidi, S.S.H.

    2014-01-01

    Two growth regulators, viz., Gibberellic acid (GA3) and Naphthalene acetic acid (NAA) and a combination of both (GA3 and NAA) were evaluated at three different levels (200, 300 and 400 meul) to check the growth rate of root, shoot, number of leaves and nodes of potato plantlets in two potato varieties, namely cardinal and SH-5, grown by meristem culture. Analysis of variance revealed highly significant differences between varieties, hormones and their interaction for all the studied traits. Mean values revealed that among two varieties Cardinal produced root length (0.70 cm), shoot length (2.50 cm), number of leaves (6.96) and number of nodes (8) are better than the SH-5 which produced root length (0.54 cm), shoot length (1.38 cm), number of leaves (4.29) and number of nodes (5.3). The variety cardinal and GA3 at 300 meul followed by 200 meul produced most suitable results. By using the concentration of 300 meul maximum root length of (1.40 cm), shoot length of (3.43 cm), number of leaves (10) and no of nodes (11) was obtained. At 200 meul, though root and shoot length obtained was very similar at 300 meul but produced less number of leaves and nodes. (author)

  19. Regulation by basic fibroblast growth factor of glycosaminoglycan biosynthesis in cultured vascular endothelial cells.

    Science.gov (United States)

    Kaji, T; Hiraga, S; Ohkawara, S; Inada, M; Yamamoto, C; Kozuka, H; Koizumi, F

    1995-05-01

    The alteration of glycosaminoglycans (GAGs) in cultured bovine aortic endothelial cells after exposure to basic fibroblast growth factor (bFGF) was investigated. It was found that the incorporation of [3H]glucosamine into GAGs was markedly increased by bFGF in both the cell layer and the conditioned medium; however, that of [35S]sulfate was not changed by the growth factor. These results indicated that bFGF enhanced the sugar-chain formation but did not affect their sulfation in endothelial GAG production. Similar changes were observed in either bovine aortic smooth-muscle cells and human fibroblastic IMR-90 cells to greater and lesser degrees, respectively. Characterization of GAGs in the endothelial cell layer and the conditioned medium revealed that bFGF enhanced both heparan sulfate and the other GAGs to a similar degree. The present data suggest that bFGF may be involved in the regulation of the blood coagulation system via altering GAGs of the vascular tissue when the endothelium was damaged.

  20. FvSet2 regulates fungal growth, pathogenicity, and secondary metabolism in Fusarium verticillioides.

    Science.gov (United States)

    Gu, Qin; Wang, Zhenzhong; Sun, Xiao; Ji, Tiantian; Huang, Hai; Yang, Yang; Zhang, Hao; Tahir, Hafiz Abdul Samad; Wu, Liming; Wu, Huijun; Gao, Xuewen

    2017-10-01

    Histone H3 lysine 36 methylation (H3K36me) is generally associated with activation of gene expression in most eukaryotic cells. However, the function of H3K36me in filamentous fungi is largely unknown. Set2 is the sole lysine histone methyltransferase (KHMTase) enzyme responsible for the methylation of H3K36 in Saccharomyces cerevisiae. In the current study, we identified a single ortholog of S. cerevisiae Set2 in Fusarium verticillioides. We report that FvSet2 is responsible for the trimethylation of H3K36 (H3K36me3). The FvSET2 deletion mutant (ΔFvSet2) showed significant defects in vegetative growth, FB 1 biosynthesis, pigmentation, and fungal virulence. Furthermore, trimethylation of H3K36 was found to be important for active transcription of genes involved in FB 1 and bikaverin biosyntheses. These data indicate that FvSet2 plays an important role in the regulation of secondary metabolism, vegetative growth and fungal virulence in F. verticillioides. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Orphan nuclear receptor NR4A1 is a negative regulator of DHT-induced rat preantral follicular growth.

    Science.gov (United States)

    Xue, Kai; Liu, Jia-yin; Murphy, Bruce D; Tsang, Benjamin K

    2012-12-01

    Nuclear receptor subfamily 4 group A member1 (NR4A1), an orphan nuclear receptor, is involved in the transcriptional regulation of thecal cell androgen biosynthesis and paracrine factor insulin-like 3 (INSL3) expression. Androgens are known to play an important regulatory role in ovarian follicle growth. Using a chronically androgenized rat model, a preantral follicle culture model and virus-mediated gene delivery, we examined the role and regulation of NR4A1 in the androgenic control of preantral follicular growth. In the present study, Ki67 staining was increased in preantral follicles on ovarian sections from 5α-dihydrotestosterone (DHT)-treated rats. Preantral follicles from DHT-treated rats cultured for 4 d exhibited increased growth and up-regulation of mRNA abundance of G(1)/S-specific cyclin-D2 (Ccnd2) and FSH receptor (Fshr). Similarly, DHT (1 μm) increased preantral follicular growth and Ccnd2 and Fshr mRNA abundance in vitro. The NR4A1 expression was high in theca cells and was down-regulated by DHT in vivo and in vitro. Forced expression of NR4A1 augmented preantral follicular growth, androstenedione production, and Insl3 expression in vitro. Inhibiting the action of androgen (with androgen receptor antagonist flutamide) or INSL3 (with INSL3 receptor antagonist INSL3 B-chain) reduced NR4A1-induced preantral follicular growth. Furthermore, NR4A1 overexpression enhanced DHT-induced preantral follicular growth, a response attenuated by inhibiting INSL3. In conclusion, DHT promotes preantral follicular growth and attenuates thecal NR4A1 expression in vivo and in vitro. Our findings are consistent with the notion that NR4A1 serves as an important point of negative feedback to minimize the excessive preantral follicle growth in hyperandrogenism.

  2. The adapter protein, Grb10, is a positive regulator of vascular endothelial growth factor signaling.

    Science.gov (United States)

    Giorgetti-Peraldi, S; Murdaca, J; Mas, J C; Van Obberghen, E

    2001-07-05

    Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and angiogenesis. Activation of VEGF receptors leads to the recruitment of SH2 containing proteins which link the receptors to the activation of signaling pathways. Here we report that Grb10, an adapter protein of which the biological role remains unknown, is tyrosine phosphorylated in response to VEGF in endothelial cells (HUVEC) and in 293 cells expressing the VEGF receptor KDR. An intact SH2 domain is required for Grb10 tyrosine phosphorylation in response to VEGF, and this phosphorylation is mediated in part through the activation of Src. In HUVEC, VEGF increases Grb10 mRNA level. Expression of Grb10 in HUVEC or in KDR expressing 293 cells results in an increase in the amount and in the tyrosine phosphorylation of KDR. In 293 cells, this is correlated with the activation of signaling molecules, such as MAP kinase. By expressing mutants of Grb10, we found that the positive action of Grb10 is independent of its SH2 domain. Moreover, these Grb10 effects on KDR seem to be specific since Grb10 has no effect on the insulin receptor, and Grb2, another adapter protein, does not mimic the effect of Grb10 on KDR. In conclusion, we propose that VEGF up-regulates Grb10 level, which in turn increases KDR molecules, suggesting that Grb10 could be involved in a positive feedback loop in VEGF signaling.

  3. Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration.

    Science.gov (United States)

    Bögel, Gábor; Gujdár, Annamária; Geiszt, Miklós; Lányi, Árpád; Fekete, Anna; Sipeki, Szabolcs; Downward, Julian; Buday, László

    2012-09-07

    Mutations in the SH3PXD2B gene coding for the Tks4 protein are responsible for the autosomal recessive Frank-ter Haar syndrome. Tks4, a substrate of Src tyrosine kinase, is implicated in the regulation of podosome formation. Here, we report a novel role for Tks4 in the EGF signaling pathway. In EGF-treated cells, Tks4 is tyrosine-phosphorylated and associated with the activated EGF receptor. This association is not direct but requires the presence of Src tyrosine kinase. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutations of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks4. Furthermore, a PX domain mutant (R43W) Tks4 carrying a reported point mutation in a Frank-ter Haar syndrome patient showed aberrant intracellular expression and reduced phosphoinositide binding. Finally, silencing of Tks4 was shown to markedly inhibit HeLa cell migration in a Boyden chamber assay in response to EGF or serum. Our results therefore reveal a new function for Tks4 in the regulation of growth factor-dependent cell migration.

  4. Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.

    Directory of Open Access Journals (Sweden)

    Kunihiko Hatanaka

    Full Text Available The fibroblast growth factor (FGF system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization.In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity.These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability.

  5. Growth regulation of HeLa cells by 1060 nm photons

    International Nuclear Information System (INIS)

    Torghele, K. F.

    1993-12-01

    Living organisms are open systems dominated by electromagnetic interaction. An essential feature of a living system is its cybernetic process which imply their capability of adaptation and sensitivity to internal and external fluctuations. The experimental results show that coherent and incoherent light of 1060 nm wavelength influences the metabolic processes and consequently the proliferation of cancer cell cultures (HeLa). Light induced regulation of HeLa cell growth depends on the cell density, the state of the cell culture and the amount of light irradiation. Best proliferation inhibiting effects can be obtained by application of 200 J/m 2 on HeLa cells in Lag-Phase and a typical cell density of 5.10 4 cells/cm 2 . Proceeding on the singlet oxygen hypothesis (KLIMA, H. et al.; 1990), it is shown mathematically that the dynamical behaviour of the NADH model is influenced by 1060 nm photons. Both, the experimental and the numerical results support our hypothesis: 1060 nm photons regulate the proliferation of HeLa cells. (author)

  6. Effect of two different plant growth regulators on production traits of sunflower

    Directory of Open Access Journals (Sweden)

    Dávid ERNST

    2016-12-01

    Full Text Available The plant growth regulators (PGR are an organic compounds that modify plant physiological processes. PGR applied to the field crops promotes photosynthesis, stimulates plant growth, improves flowering and protects plants against unfavourable year weather conditions. Listed is an assumption to the yield of high quality. The effects of year weather conditions, biological material (hybrids and foliar application of two different PGR (Terra-Sorb® Foliar – containing free amino acids and Unicum® – containing Abiestins® on the yield-forming parameters, seed yield and the oil content in seeds of three selected hybrids of sunflower (NK Brio, NK Neoma, NK Ferti were studied in this paper. The field poly-factorial experiments were realized during two growing seasons of 2012 and 2013. The experimental area is situated in the maize-growing region (climatic region: warm; climatic sub-region: mild dry or dry; climatic zone: warm and dry, with mild winter and long sunshine and soil is silt loam Haplic Luvisol. The climatic conditions in chosen experimental years were different in quantities and distribution of precipitation at main growth period of sunflower plants (June to August and allows evaluating the yield stability between used hybrids and foliar treatments. The results showed that the application of selected PGR has contributed to an increase of sunflower seed yield, mainly through increase the weight of thousand seeds (rp = 0.761; P < 0.001. Similarly, oil content in seeds was significantly higher in treatments with PGR, especially with preparation Terra-Sorb® Foliar containing free amino acids. The study describes the relationship between quality (oil content in seeds and quantity (seed yield of sunflower production (rp = ‒0.41; P < 0.01. Results showed that PGR can be an important rationalization tool of the sunflower cultivation technology.

  7. Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens.

    Science.gov (United States)

    Lin, Shumao; Li, Hongmei; Mu, Heping; Luo, Wen; Li, Ying; Jia, Xinzheng; Wang, Sibing; Jia, Xiaolu; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

    2012-07-10

    A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3' untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. There is a critical miRNA, let-7b

  8. Basic Fibroblast Growth Factor Regulates Persistent ERK Osciliations in Premaligant but not Malignant JB6 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Thomas J.; Shankaran, Harish; Wiley, H. S.; Opresko, Lee K.; Chrisler, William B.; Quesenberry, Ryan D.

    2010-05-02

    basic fibroblast growth factor (bFGF or FGF2) plays an important role in epidermal wound healing in vivo and is associated with a persistent increased in the extracellular signal-regulated kinase (ERK) pathway in vitro. Here we have examined whether bFGF induces the closure of an experimental scratch wound in JB6 mouse epidermal cells and have explored the regulation of the ERK pathway by bFGF in the context of kinase oscillations. bFGF stimulation is associated with increases in cellular phospho-ERK and phospho-c-Jun levels. In addition, bFGF increases cell proliferation and a change in cell morphology (stellate appearance) in a dose-dependent fashion (0.1 – 100 ng/ml). bFGF treatment also promoted the closure of an experimental scratch wound in vitro. JB6 cells were stably transfected with an ERK1-GFP chimera to follow temporal ERK subcellular distribution patterns. We observe a persistent upregulation of the ERK pathway, as evidenced by a significant increase in nuclear ERK1-GFP levels at time points up to 24 hr after bFGF treatment. Interestingly, at the single cell level, ERK is observed to oscillate between nuclear and cytosolic compartments in response to bFGF treatment. Because this oscillatory behavior is asynchronous in the cell population, it is only clearly resolved at the single cell level. Collectively, data presented here are consistent with an important role for bFGF in wound healing and suggest a more complex regulation of the ERK pathway by bFGF than has previously been appreciated.

  9. Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

    Science.gov (United States)

    Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2015-02-01

    Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

  10. Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Jing; Lauf, Peter K; Adragna, Norma C

    2003-03-01

    Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

  11. Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival.

    Directory of Open Access Journals (Sweden)

    Audrey Dayon

    Full Text Available BACKGROUND: Sphingosine kinase-1 (SphK1 is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a

  12. Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

    International Nuclear Information System (INIS)

    Ahmed, M.

    2003-01-01

    Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

  13. Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

    Energy Technology Data Exchange (ETDEWEB)

    Sindi, Ramya A., E-mail: ramya.sindi2010@my.ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); School of Applied Medical Sciences, Umm Al-Qura University, Makkah (Saudi Arabia); Harris, Wayne [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Arnott, Gordon [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Flaskos, John [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Lloyd Mills, Chris [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Hargreaves, Alan J., E-mail: alan.hargreaves@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2016-10-01

    Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

  14. Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

    International Nuclear Information System (INIS)

    Sindi, Ramya A.; Harris, Wayne; Arnott, Gordon; Flaskos, John; Lloyd Mills, Chris; Hargreaves, Alan J.

    2016-01-01

    Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

  15. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Masatake, E-mail: fujimura@nimd.go.jp [Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto (Japan); Usuki, Fusako [Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto (Japan); Cheng, Jinping; Zhao, Wenchang [School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  16. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Cheng, Jinping; Zhao, Wenchang

    2016-01-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  17. Receptor-like kinases as surface regulators for RAC/ROP-mediated pollen tube growth and interaction with the pistil

    Science.gov (United States)

    Zou, Yanjiao; Aggarwal, Mini; Zheng, Wen-Guang; Wu, Hen-Ming; Cheung, Alice Y.

    2011-01-01

    Background RAC/ROPs are RHO-type GTPases and are known to play diverse signalling roles in plants. Cytoplasmic RAC/ROPs are recruited to the cell membrane and activated in response to extracellular signals perceived and mediated by cell surface-located signalling assemblies, transducing the signals to regulate cellular processes. More than any other cell types in plants, pollen tubes depend on continuous interactions with an extracellular environment produced by their surrounding tissues as they grow within the female organ pistil to deliver sperm to the female gametophyte for fertilization. Scope We review studies on pollen tube growth that provide compelling evidence indicating that RAC/ROPs are crucial for regulating the cellular processes that underlie the polarized cell growth process. Efforts to identify cell surface regulators that mediate extracellular signals also point to RAC/ROPs being the molecular switches targeted by growth-regulating female factors for modulation to mediate pollination and fertilization. We discuss a large volume of work spanning more than two decades on a family of pollen-specific receptor kinases and some recent studies on members of the FERONIA family of receptor-like kinases (RLKs). Significance The research described shows the crucial roles that two RLK families play in transducing signals from growth regulatory factors to the RAC/ROP switch at the pollen tube apex to mediate and target pollen tube growth to the female gametophyte and signal its disintegration to achieve fertilization once inside the female chamber. PMID:22476487

  18. Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.

    Directory of Open Access Journals (Sweden)

    Weiguang Wang

    2016-10-01

    Full Text Available TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO, global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3 mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish

  19. Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate

    Science.gov (United States)

    Wang, Weiguang; Song, Buer; Anbarchian, Teni; Shirazyan, Anna

    2016-01-01

    TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3) mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx) mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs) were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish this by binding to

  20. From Normalcy to Neoplasia. The Role of Epithelial-Stromal Interactions in Regulating Mammary Growth and Differentiation

    Science.gov (United States)

    2000-08-01

    stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J. Mammary Gland Biol. Neoplasia 2, 393-402. Debatin...Birkedal-Hansen (1999) MT1-MMP- deficient mice develop dwarfism , osteopenia, arthritis, and connective tissue disease due to inadequate collagen...al., 1988). Ligands of the epidermal growth hormonally regulated ductal development during puberty and factor receptor (EGFR) are believed to be

  1. RNF11 is a multifunctional modulator of growth factor receptor signalling and transcriptional regulation.

    Science.gov (United States)

    Azmi, Peter; Seth, Arun

    2005-11-01

    Our laboratory has found that the 154aa RING finger protein 11 (RNF11), has modular domains and motifs including a RING-H2 finger domain, a PY motif, an ubiquitin interacting motif (UIM), a 14-3-3 binding sequence and an AKT phosphorylation site. RNF11 represents a unique protein with no other known immediate family members yet described. Comparative genetic analysis has shown that RNF11 is highly conserved throughout evolution. This may indicate a conserved and non-redundant role for the RNF11 protein. Molecular binding assays using RNF11 have shown that RNF11 has important roles in growth factor signalling, ubiquitination and transcriptional regulation. RNF11 has been shown to interact with HECT-type E3 ubiquitin ligases Nedd4, AIP4, Smurf1 and Smurf2, as well as with Cullin1, the core protein in the multi-subunit SCF E3 ubiquitin ligase complex. Work done in our laboratory has shown that RNF11 is capable of antagonizing Smurf2-mediated inhibition of TGFbeta signalling. Furthermore, RNF11 is capable of degrading AMSH, a positive regulator of both TGFbeta and EGFR signalling pathways. Recently, we have found that RNF11 can directly enhance TGFbeta signalling through a direct association with Smad4, the common signal transducer and transcription factor in the TGFbeta, BMP, and Activin pathways. Through its association with Smad4 and other transcription factors, RNF11 may have a role in direct transcriptional regulation. Our laboratory and others have found nearly 80 protein interactions for RNF11, placing RNF11 at the cross-roads of cell signalling and transcriptional regulation. RNF11 is highly expressed in breast tumours. Deregulation of RNF11 function may prove to be harmful to patient therapeutic outcomes. RNF11 may therefore provide a novel target for cancer therapeutics. The purpose of this review is to discuss the role of RNF11 in cell signalling and transcription factor modulation with special attention given to the ubiquitin-proteasomal pathway, TGFbeta

  2. Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene

    Science.gov (United States)

    Ifere, Godwin O.; Equan, Anita; Gordon, Kereen; Nagappan, Peri; Igietseme, Joseph U.; Ananaba, Godwin A.

    2010-01-01

    Background The purpose of our study was to show the distinction between the apoptotic and anti-proliferative signaling of phytosterols and cholesterol enrichment in prostate cancer cell lines, mediated by the differential transcription of caveolin-1, and N-myc downstream regulated gene1 (NDRG1), a pro-apoptotic androgen-regulated tumor suppressor. Methods PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 72 h, followed by trypan blue dye exclusion measurement of necrosis and cell growth measured with a Coulter counter. Sterol induction of cell growth-suppressor gene expression was evaluated by mRNA transcription using RT-PCR, while cell cycle analysis was performed by FACS analysis. Altered expression of Ndrg1 protein was confirmed by Western blot analysis. Apoptosis was evaluated by real time RT-PCR amplification of P53, Bcl-2 gene and its related pro- and anti-apoptotic family members. Results Physiological doses (16 µM) of cholesterol and phytosterols were not cytotoxic in these cells. Cholesterol enrichment promoted cell growth (Pphytosterols significantly induced growth-suppression (Pphytosterols decreased mitotic subpopulations. We demonstrated for the first time that cholesterols concertedly attenuated the expression of caveolin-1(cav-1) and NDRG1 genes in both prostate cancer cell lines. Phytosterols had the opposite effect by inducing overexpression of cav-1, a known mediator of androgen-dependent signals that presumably control cell growth or apoptosis. Conclusions Cholesterol and phytosterol treatment differentially regulated the growth of prostate cancer cells and the expression of p53 and cav-1, a gene that regulates androgen-regulated signals. These sterols also differentially regulated cell cycle arrest, downstream pro-apoptotic androgen-regulated tumor-suppressor, NDRG1 suggesting that cav-1 may mediate pro-apoptotic NDRG1 signals. Elucidation of the mechanism for sterol modulation of growth and apoptosis signaling

  3. Changes in the physiological activity of soybean (Glycine max L. Merr. under the influence of exogenous growth regulators

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    Anna Nowak

    2015-07-01

    Full Text Available In a two-year pot experiment (2008–2009 conducted at the Vegetation Hall, West Pomeranian University of Technology in Szczecin, we investigated the influence of exogenous growth regulators, i.e. indole-3-butyric acid (IBA and 6-benzylaminopurine (BAP and their mixture, on the activity of gas exchange and selected physiological features of soybeans (Glycine max L. Merr.. The experimental factors included the following Polish soybean cultivars: ‘Aldana’, ‘Progres’ and ‘Jutro’. During plant growth, CO2 assimilation (A, transpiration rate (E, stomatal conductance (gs, and substomatal CO2 concentration (ci were determined. Two soybean cultivars, i.e. ‘Jutro’ and ‘Progres’, showed a significant increase in the intensity of assimilation and transpiration after using all kinds of growth regulators as compared with the control plants. It was found that the ‘Jutro’ cultivar, after using a mixture of growth regulators (IBA + BAP, was characterized by the significantly highest CO2 assimilation (A and transpiration (E as well as the highest stomatal conductance (gs. The ‘Aldana’ cultivar, on the other hand, responded by a significant reduction in the transpiration rate, stomatal conductance and subsomatal CO2 concentration. The spraying of the plants with exogenous growth regulators had a significant influence on the increase in the number of stomata and stomatal pore length, mostly on the lower epidermis of the lamina. It was also found that plants from the ‘Jutro’ and ‘Aldana’ cultivars sprayed with IBA and IBA + BAP were characterized by the highest yield, as compared with the control plants. In the case of the ‘Jutro’ cultivar, after using the growth regulators, a positive correlation was observed between the assimilation and transpiration rates and the length of stomata, which in consequence produced increased yields.

  4. Melatonin Is Involved in Regulation of Bermudagrass Growth and Development and Response to Low K+ Stress

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    Liang Chen

    2017-11-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine plays critical roles in plant growth and development and during the response to multiple abiotic stresses. However, the roles of melatonin in plant response to K+ deficiency remain largely unknown. In the present study, we observed that the endogenous melatonin contents in bermudagrass were remarkably increased by low K+ (LK treatment, suggesting that melatonin was involved in bermudagrass response to LK stress. Further phenotype analysis revealed that exogenous melatonin application conferred Bermudagrass enhanced tolerance to LK stress. Interestingly, exogenous melatonin application also promoted bermudagrass growth and development at normal condition. Furthermore, the K+ contents measurement revealed that melatonin-treated plants accumulated more K+ in both shoot (under both control and LK condition and root tissues (under LK condition compared with those of melatonin non-treated plants. Expression analysis indicated that the transcripts of K+ transport genes were significantly induced by exogenous melatonin treatment in bermudagrass under both control and LK stress conditions, especially under a combined treatment of LK stress and melatonin, which may increase accumulation of K+ content profoundly under LK stress and thereby contributed to the LK-tolerant phenotype. In addition, we investigated the role of melatonin in the regulation of photosystem II (PSII activities under LK stress. The chlorophyll fluorescence transient (OJIP curves were obviously higher in plants grown in LK with melatonin (LK+Mel than those of plants grown in LK medium without melatonin application for 1 or 2 weeks, suggesting that melatonin plays important roles in PSII against LK stress. After a combined treatment of LK stress and melatonin, the values for performance indexes (PIABS, PITotal, and PICS, flux ratios (φP0, ΨE0, and φE0 and specific energy fluxes (ETO/RC were significantly improved compared with those of LK

  5. Modeling the Impact of Growth and Leptin Deficits on the Neuronal Regulation of Blood Pressure

    Science.gov (United States)

    Steinbrekera, Baiba; Roghair, Robert

    2016-01-01

    The risk of hypertension is increased by intrauterine growth restriction (IUGR) and preterm birth. In the search for modifiable etiologies for this life-threatening cardiovascular morbidity, a number of pathways have been investigated, including excessive glucocorticoid exposure, nutritional deficiency, and aberration in sex hormone levels. As a neurotrophic hormone intimately involved in cardiovascular regulation whose levels are influenced by glucocorticoids, nutritional status and sex hormones, leptin has emerged as a putative etiologic and thus therapeutic agent. As a product of maternal and late fetal adipocytes as well as the placenta, circulating leptin typically surges late in gestation and declines following delivery until the infant consumes sufficient leptin-containing breast milk or accrues sufficient leptin-secreting adipose tissue to reestablish circulating levels. The leptin deficiency seen in IUGR infants is a multifactorial manifestation of placental insufficiency, exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant suffers from the same cascade of events, including separation from the placenta, antenatal steroid exposure and persistently underdeveloped adipose depots. Preterm infants remain leptin deficient beyond term gestation, rendering them susceptible to neurodevelopmental impairment and subsequent cardiovascular dysregulation. This pathologic pathway is efficiently modeled by placing neonatal mice into atypically large litters, thereby recapitulating the perinatal growth restriction-adult hypertension phenotype. In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension. Further pathway interrogation and clinical translation are needed to fully test the therapeutic potential of perinatal leptin supplementation. PMID:27613336

  6. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Tomblin, Justin K.; Salisbury, Travis B.

    2014-01-01

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR

  7. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tomblin, Justin K.; Salisbury, Travis B., E-mail: salisburyt@marshall.edu

    2014-01-17

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.

  8. Extracellular calmodulin regulates growth and cAMP-mediated chemotaxis in Dictyostelium discoideum

    International Nuclear Information System (INIS)

    O’Day, Danton H.; Huber, Robert J.; Suarez, Andres

    2012-01-01

    Highlights: ► Extracellular calmodulin is present throughout growth and development in Dictyostelium. ► Extracellular calmodulin localizes within the ECM during development. ► Extracellular calmodulin inhibits cell proliferation and increases chemotaxis. ► Extracellular calmodulin exists in eukaryotic microbes. ► Extracellular calmodulin may be functionally as important as intracellular calmodulin. -- Abstract: The existence of extracellular calmodulin (CaM) has had a long and controversial history. CaM is a ubiquitous calcium-binding protein that has been found in every eukaryotic cell system. Calcium-free apo-CaM and Ca 2+ /CaM exert their effects by binding to and regulating the activity of CaM-binding proteins (CaMBPs). Most of the research done to date on CaM and its CaMBPs has focused on their intracellular functions. The presence of extracellular CaM is well established in a number of plants where it functions in proliferation, cell wall regeneration, gene regulation and germination. While CaM has been detected extracellularly in several animal species, including frog, rat, rabbit and human, its extracellular localization and functions are less well established. In contrast the study of extracellular CaM in eukaryotic microbes remains to be done. Here we show that CaM is constitutively expressed and secreted throughout asexual development in Dictyostelium where the presence of extracellular CaM dose-dependently inhibits cell proliferation but increases cAMP mediated chemotaxis. During development, extracellular CaM localizes within the slime sheath where it coexists with at least one CaMBP, the matricellular CaM-binding protein CyrA. Coupled with previous research, this work provides direct evidence for the existence of extracellular CaM in the Dictyostelium and provides insight into its functions in this model amoebozoan.

  9. Insulin-like growth factor-II receptors in cultured rat hepatocytes: regulation by cell density

    International Nuclear Information System (INIS)

    Scott, C.D.; Baxter, R.C.

    1987-01-01

    Insulin-like growth factor-II (IGF-II) receptors in primary cultures of adult rat hepatocytes were characterized and their regulation by cell density examined. In hepatocytes cultured at 5 X 10(5) cells per 3.8 cm2 plate [ 125 I]IGF-II bound to specific, high affinity receptors (Ka = 4.4 +/- 0.5 X 10(9) l/mol). Less than 1% cross-reactivity by IGF-I and no cross-reactivity by insulin were observed. IGF-II binding increased when cells were permeabilized with 0.01% digitonin, suggesting the presence of an intracellular receptor pool. Determined by Scatchard analysis and by polyacrylamide gel electrophoresis after affinity labeling, the higher binding was due solely to an increase in binding sites present on 220 kDa type II IGF receptors. In hepatocytes cultured at low densities, the number of cell surface receptors increased markedly, from 10-20,000 receptors per cell at a culture density of 6 X 10(5) cells/well to 70-80,000 receptors per cell at 0.38 X 10(5) cells/well. The increase was not due simply to the exposure of receptors from the intracellular pool, as a density-related increase in receptors was also seen in cells permeabilized with digitonin. There was no evidence that IGF binding proteins, either secreted by hepatocytes or present in fetal calf serum, had any effect on the measurement of receptor concentration or affinity. We conclude that rat hepatocytes in primary culture contain specific IGF-II receptors and that both cell surface and intracellular receptors are regulated by cell density

  10. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2018-04-01

    Full Text Available The neurohypophyseal hormone oxytocin (Oxt has been shown to stimulate prolactin (Prl synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr, namely isotocin (Ist receptor 1 (Istr1 and 2 (Istr2, were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  11. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Science.gov (United States)

    Yang, Wei; Zhang, Ning; Shi, Boyang; Zhang, Shen; Zhang, Lihong; Zhang, Weimin

    2018-01-01

    The neurohypophyseal hormone oxytocin (Oxt) has been shown to stimulate prolactin (Prl) synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr), namely isotocin (Ist) receptor 1 (Istr1) and 2 (Istr2), were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh) cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  12. Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF)

    Energy Technology Data Exchange (ETDEWEB)

    Serrano, Isabel; Diez-Marques, Maria L.; Rodriguez-Puyol, Manuel [Department of Physiology, University of Alcala, Alcala de Henares, Madrid (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Instituto Reina Sofia de Investigacion Nefrologica (Spain); Herrero-Fresneda, Inmaculada [Nephrology Unit, IDIBELL, Hospital de Bellvitge, Barcelona (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Garcia del Moral, Raimundo [Department of Pathology, University of Granada (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Dedhar, Shoukat [Department of Integrative Oncology, BC Cancer Research Center, Vancouver, BC (Canada); Ruiz-Torres, Maria P., E-mail: mpiedad.ruiz@uah.es [Department of Physiology, University of Alcala, Alcala de Henares, Madrid (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Instituto Reina Sofia de Investigacion Nefrologica (Spain); Rodriguez-Puyol, Diego [Nephrology Unit, Hospital Universitario Principe de Asturias, Alcala de Henares, Madrid (Spain); Red de Investigacion Renal Cooperativa (RedinRen) (Spain); Instituto Reina Sofia de Investigacion Nefrologica (Spain)

    2012-11-15

    Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing. -- Highlights: Black-Right-Pointing-Pointer ILK deletion results in decreased HGF expression and delayed scratch wound repair. Black-Right-Pointing-Pointer PI3K/ILK/AKT pathway signals through HGF to regulate wound healing. Black-Right-Pointing-Pointer An ILK-dependent increase in HGF expression is responsible for wound healing in vivo. Black-Right-Pointing-Pointer ILK-KO mice are used to confirm the requirement for ILK function in wound healing. Black-Right-Pointing-Pointer Human HGF treatment restores delayed wound closure in vitro and in vivo.

  13. Toward epigenetic and gene regulation models of specific language impairment: looking for links among growth, genes, and impairments

    Directory of Open Access Journals (Sweden)

    Rice Mabel L

    2012-11-01

    Full Text Available Abstract Children with specific language impairment (SLI are thought to have an inherited form of language impairment that spares other developmental domains. SLI shows strong heritability and recent linkage and association studies have replicated results for candidate genes. Regulatory regions of the genes may be involved. Behavioral growth models of language development of children with SLI reveal that the onset of language is delayed, and the growth trajectories of children with SLI parallel those of younger children without SLI. The rate of language acquisition decelerates in the pre-adolescent period, resulting in immature language levels for the children with SLI that persist into adolescence and beyond. Recent genetic and epigenetic discoveries and models relevant to language impairment are reviewed. T cell regulation of onset, acceleration, and deceleration signaling are described as potential conceptual parallels to the growth timing elements of language acquisition and impairment. A growth signaling disruption (GSD hypothesis is proposed for SLI, which posits that faulty timing mechanisms at the cellular level, intrinsic to neurocortical functioning essential for language onset and growth regulation, are at the core of the growth outcomes of SLI. The GSD highlights the need to document and account for growth patterns over childhood and suggests needed directions for future investigation.

  14. Who is the new sheriff in town regulating boreal forest growth?

    Science.gov (United States)

    Park Williams, A.; Xu, Chonggang; McDowell, Nate G.

    2011-12-01

    Climate change appears to be altering boreal forests. One recently observed symptom of these changes has been an apparent weakening of the positive relationship between high-latitude boreal tree growth and temperature at some sites (D'Arrigo et al 2008). This phenomenon is referred to as the 'divergence problem' or 'divergence effect' and is thought to reflect a non-linear relationship between temperature and tree growth, where recent warming has allowed other factors besides growing-season temperature to emerge as dominant regulators of annual growth rates. Figure 1 demonstrates this divergence phenomenon with records of tree-ring widths collected from 59 populations of white spruce in Alaska 1. Key tendencies among these populations include: (1) growth is most sensitive to temperature during relatively cold growing seasons (figure 1(a)), (2) populations at colder sites are more sensitive to temperature than those at warmer sites are (figure 1(a)), and (3) growth at warmer sites may respond negatively to increased temperature beyond some optimal growing-season temperature (figure 1(b)). Since temperature is rising rapidly at high latitudes, one interpretation of figures 1(a) and (b) is that warming has promoted increased growth at colder sites, but caused growth to plateau or slow at warmer sites. Corroborating this interpretation, satellite imagery and tree-ring data indicate increasing vegetation productivity near the forest-tundra boundary but declining productivity in warmer regions within forest interiors (e.g., Bunn and Goetz 2006, Beck and Goetz 2011, Beck et al 2011, Berner et al 2011). Will continued warming cause a northward migration of boreal forests, with mortality in the warmer, southern locations and expansion into the colder tundra? This question is difficult to answer because many factors besides temperature influence boreal forest dynamics. Widespread productivity declines within interior boreal forests appear to be related to warming

  15. Quantitative assessment of neurite outgrowth in human embryonic stem-cell derived neurons using automated high-content image analysis

    Science.gov (United States)

    During development neurons undergo a number of morphological changes including neurite outgrowth from the cell body. Exposure to neurotoxicants that interfere with this process may cause in permanent deficits in nervous system function. While many studies have used rodent primary...

  16. Effect of Plant Growth Regulator on Red Onion Cultivation from True Seed Shallot (TSS

    Directory of Open Access Journals (Sweden)

    Tri Sudaryono

    2018-01-01

    Full Text Available Red onion is one of the strategic horticultural commodities, considering this commodity is very high consumption as a daily spice and fluctuating price. Therefore is not surprising that these commodities are contributing to inflation. Efforts to meet increasing consumption needs, it is necessary to find the right strategy to increase domestic red onion production. One of the strategies considered to increase domestic red onion production is the use of botanical seed (TSS as a source of seed on shallot cultivation. There are 2 main weaknesses of red onion cultivation with TSS as a source of seeds. The two weaknesses are TSS low growing power, which is naturally only in the 50-60 % range and the number of tubers produced is less than 3 cloves per plant. In order to solve the problem, research has been done to know the effect of plant growth regulator on the growth and red onion production from TSS and also get the description of red onion farming from TSS and tuber as seed source. The research was conducted from June to November 2017 at BPP Pare, Kediri Regency, East Java. The results showed that the use of young coconut water on TSS obtained red onion plants are able to produce the number of tubers per plant more than 3 cloves. In detail as much as 22.22 % produces the number of tubers range 4-5 per plant; 56.56 % yields 5-6 bulb range; and as much as 22.22 % produces tubers > 6. As well, wet weight of tubers when harvested weighing more than 99 g per plant. If converted per hectare, TSS red onion plants treated with young coconut water can produce a range of 30 -35 tons of wet bulb. This production is doubled compared to the production of shallots grown from tubers. Based on the analysis of the farm, red onion from TSS treated with young coconut water gives a profit of Rp 224,860,000 per hectare with B/C ratio of 3.397. This profit is more than 1.75 times compared to the profit of red onion tuber farming which is only Rp 93.787.000, - with B

  17. Periosteal PTHrP regulates cortical bone modeling during linear growth in mice.

    Science.gov (United States)

    Wang, Meina; VanHouten, Joshua N; Nasiri, Ali R; Tommasini, Steven M; Broadus, Arthur E

    2014-07-01

    The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone-related peptide (PTHrP) expressed in the fibrous layer of the periosteum (PO) drives the osteoclastic (OC) resorption that models the metaphyseal-diaphyseal junction (MDJ) in the proximal tibia and fibula during linear growth. PTHrP was conditionally deleted (cKO) in the PO via Scleraxis gene targeting (Scx-Cre). In the lateral tibia, cKO of PTHrP led to a failure of modeling, such that the normal concave MDJ was replaced by a mound-like deformity. This was accompanied by a failure to induce receptor activator of NF-kB ligand (RANKL) and a 75% reduction in OC number (P ≤ 0.001) on the cortical surface. The MDJ also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (P ≤ 0.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the PO surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in CD-1 mice that was so moth-eaten that a clear PO surface could not be identified. The cKO fibula displayed a remarkable phenotype, with a misshapen club-like metaphysis and an enlargement in the 3D size of the entire bone, manifest as a 40-45% increase in the PO circumference at the MDJ (P ≤ 0.001) as well as the mid-diaphysis (P ≤ 0.001). These tibial and fibular phenotypes were reproduced in a Scx-Cre-driven RANKL cKO mouse. We conclude that PTHrP in the fibrous PO mediates the modeling of the MDJ of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone. © 2014 Anatomical Society.

  18. Maize yield and quality in response to plant density and application of a novel plant growth regulator

    NARCIS (Netherlands)

    Zhang, Q.; Zhang, L.; Evers, J.B.; Werf, van der W.; Zhang, W.; Duan, L.

    2014-01-01

    Farmers in China have gradually increased plant density in maize to achieve higher yields, but this has increased risk of lodging due to taller and weaker stems at higher plant densities. Plant growth regulators can be used to reduce lodging risk. In this study, for the first time, the performance

  19. Antisense down-regulation of 4CL expression alters lignification, tree growth, and saccharification potential of field-grown poplar

    Science.gov (United States)

    Steven L. Voelker; Barbara Lachenbruch; Frederick C. Meinzer; Michael Jourdes; Chanyoung Ki; Ann M. Patten; Laurence B. Davin; Norman G. Lewis; Gerald A. Tuskan; Lee Gunter; Stephen R. Decker; Michael J. Selig; Robert Sykes; Michael E. Himmel; Peter Kitin; Olga Shevchenko; Steven H. Strauss

    2010-01-01

    Transgenic down-regulation of the Pt4CL1 gene family encoding 4-coumarate:coenzyme A ligase (4CL) has been reported as a means for reducing lignin content in cell walls and increasing overall growth rates, thereby improving feedstock quality for paper and bioethanol production. Using hybrid poplar (Populus tremula...

  20. Iron-regulated metabolites of plant growth-promoting Pseudomonas fluorescens WCS374 : Their role in induced systemic resistance

    NARCIS (Netherlands)

    Djavaheri, M.

    2007-01-01

    The plant growth-promoting rhizobacterium Pseudomonas fluorescens WCS374r effectively suppresses fusarium wilt in radish by induced systemic resistance (ISR). In radish, WCS374r-mediated ISR depends partly on iron-regulated metabolites. Under iron-limiting conditions, P. fluorescens WCS374r produces

  1. Treatment of grapevines with prohexadione calcium as a growth regulator. The influence on production, winemaking and sensory characteristics of wines

    Directory of Open Access Journals (Sweden)

    Luis Vaquero-Fernández

    2009-09-01

    Significance and impact of study: ProCa as a growth regulator may be an option for a quality vitiviniculture. No previous studies have been published on applications of ProCa in grapevines in either Europe or in cv. Tempranillo. Additionally, studies with other varieties have not demonstrated sensory improvements in wines obtained from treated vines.

  2. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, r