36 results on '"Ann Acheson"'
Search Results
2. Sharing Isn’t Easy: Food Waste and Food Redistribution in Maine K–12 Schools
- Author
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Brieanne Berry and Ann Acheson
- Subjects
food waste ,food redistribution ,food insecurity ,policy uncertainty ,education ,Social Sciences ,Political institutions and public administration (General) ,JF20-2112 - Published
- 2017
3. Celebrating Maine Policy Review’s 20th Anniversary
- Author
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Ann Acheson, Ralph Townsend, Kathryn Hunt, Merton G. Henry, Peter Mills, and Linda Silka
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maine ,public policy ,policy communications ,Social Sciences ,Political institutions and public administration (General) ,JF20-2112 - Published
- 2012
4. Family Economic Security
- Author
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Ann Acheson
- Subjects
maine ,poverty ,poverty programs ,poverty policies ,Social Sciences ,Political institutions and public administration (General) ,JF20-2112 - Published
- 2009
5. Poverty in Maine
- Author
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Ann Acheson
- Subjects
maine poverty ,poverty policy ,poverty benefits ,Social Sciences ,Political institutions and public administration (General) ,JF20-2112 - Published
- 2007
6. Looking Back, Looking Forward
- Author
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Ann Acheson
- Published
- 2016
7. Co-infusion with a TrkB-Fc Receptor Body Carrier Enhances BDNF Distribution in the Adult Rat Brain
- Author
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Terence E Ryan, Peter S. DiStefano, Stanley J. Wiegand, Ann Acheson, Ronald M. Lindsay, John S. Rudge, Judith A. Siuciak, Susan D. Croll, and Catherine R. Chesnutt
- Subjects
Male ,medicine.medical_specialty ,Recombinant Fusion Proteins ,Enzyme-Linked Immunosorbent Assay ,Receptors, Fc ,Receptors, Nerve Growth Factor ,Tropomyosin receptor kinase B ,Spodoptera ,Hippocampus ,Polymerase Chain Reaction ,Receptor tyrosine kinase ,Rats, Sprague-Dawley ,Developmental Neuroscience ,Neurotrophic factors ,Internal medicine ,medicine ,Animals ,Humans ,Neuropeptide Y ,Phosphorylation ,Receptor, Ciliary Neurotrophic Factor ,Injections, Intraventricular ,Brain-derived neurotrophic factor ,biology ,Brain-Derived Neurotrophic Factor ,musculoskeletal, neural, and ocular physiology ,Brain ,Receptor Protein-Tyrosine Kinases ,Neuropeptide Y receptor ,Fusion protein ,Rats ,Up-Regulation ,Neuroprotective Agents ,Endocrinology ,nervous system ,Neurology ,Ectodomain ,embryonic structures ,biology.protein ,Neurotrophin - Abstract
Fusion proteins comprising the Fc domain of human IgG and extracellular domains of receptor tyrosine kinases can neutralize the activity of their cognate ligands when administered in molar excess. We have generated a fusion protein using the ectodomain of TrkB (TrkB-Fc). Although the ability of TrkB-Fc to neutralize the activity of brain-derived neurotrophic factor (BDNF) in vitro has been demonstrated, there have been no conclusive demonstrations of its ability to neutralize the activity of BDNF in vivo. We co-infused TrkB-Fc with BDNF into the cortex and hippocampus of adult rats to determine whether TrkB-Fc would interfere with the ability of BDNF to upregulate neuropeptide Y (NPY). We report here that rather than neutralizing the activity of exogenous BDNF, co-infusion with the TrkB-Fc fusion protein greatly increased the volume of tissue in which neuropeptide Y immunostaining was upregulated. In addition, TrkB-Fc greatly enhanced BDNF's distribution through adult brain parenchyma. TrkB-Fc also markedly increased the otherwise limited diffusion of BDNF into brain parenchyma following intraventricular infusion. These results show that rather than neutralizing or sequestering BDNF, the TrkB-Fc, at close to molar equivalence to BDNF, can function as a carrier for BDNF and thus enhance the delivery or penetration of this polypeptide into the brain.
- Published
- 1998
8. Axotomy Upregulates the Anterograde Transport and Expression of Brain-Derived Neurotrophic Factor by Sensory Neurons
- Author
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Trang Nguyen, Ann Acheson, John S. Park, Rory A. J. Curtis, Vivien Wong, Ronald M. Lindsay, Andrew Timmes, Kenneth D. Cliffer, Peter S. DiStefano, and James R. Tonra
- Subjects
Male ,Nerve Crush ,Calcitonin Gene-Related Peptide ,medicine.medical_treatment ,Neurotrophin-3 ,Substance P ,Axonal Transport ,Article ,Rhizotomy ,Rats, Sprague-Dawley ,Neurotrophin 3 ,Dorsal root ganglion ,Ganglia, Spinal ,medicine ,Animals ,Nerve Growth Factors ,Neurons, Afferent ,RNA, Messenger ,Brain-derived neurotrophic factor ,biology ,Brain-Derived Neurotrophic Factor ,General Neuroscience ,Axotomy ,Nerve injury ,Sciatic nerve injury ,medicine.disease ,Sciatic Nerve ,Rats ,Cell biology ,medicine.anatomical_structure ,nervous system ,Peripheral nervous system ,Peripheral nerve injury ,biology.protein ,medicine.symptom ,Neuroscience - Abstract
In addition to the known retrograde transport of neurotrophins, it is now evident that endogenous brain-derived neurotrophic factor (BDNF) is transported in the anterograde direction in peripheral and central neurons. We used a double-ligation procedure that distinguishes between anterograde and retrograde flow to quantify the anterograde transport of endogenous neurotrophins and neuropeptides in the peripheral nervous system before and after axotomy. BDNF accumulation proximal to the ligation (anterograde transport) was twice that distal to the ligation (retrograde direction). Anterograde transport of nerve growth factor and neurotrophin-3 was not evident. Furthermore, BDNF anterograde transport increased 3.5-fold within 24 hr after sciatic nerve injury or dorsal rhizotomy. Anterograde transport of substance P and calcitonin gene-related peptide decreased after peripheral nerve lesion, demonstrating that there was no generalized increase in anterograde transport. To determine the source of the anterogradely transported BDNF, we performedin situhybridization in a variety of tissues before and after axotomy. Expression of BDNF mRNA in proximal nerve segments did not change with treatment, showing that the increased accumulation of BDNF was not a result of increased local synthesis. BDNF mRNA and protein were expressed by dorsal root ganglion sensory neurons but not by motor neurons. BDNF mRNA expression was increased 1 d after nerve injury, and BDNF protein was also increased twofold to threefold, suggesting that sensory neurons are the major contributing source of the increased BDNF traffic in the sciatic nerve. Our results suggest that increased anterogradely transported BDNF plays a role in the early neuronal response to peripheral nerve injury at sites distal to the cell body.
- Published
- 1998
9. Anterograde transport of brain-derived neurotrophic factor and its role in the brain
- Author
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J M Conner, Ronald M. Lindsay, Stanley J. Wiegand, Ning Cai, Ann Acheson, C A Altar, M Juhasz, and T Bliven
- Subjects
Male ,Central nervous system ,Axonal Transport ,Rats, Sprague-Dawley ,Mice ,Neurotrophic factors ,medicine ,Animals ,Humans ,Neurons, Afferent ,RNA, Messenger ,Brain-derived neurotrophic factor ,Multidisciplinary ,biology ,Brain-Derived Neurotrophic Factor ,Brain ,Anatomy ,Denervation ,Immunohistochemistry ,Rats ,Neostriatum ,Parvalbumins ,medicine.anatomical_structure ,nervous system ,Peripheral nervous system ,Mutation ,biology.protein ,Retrograde signaling ,Axoplasmic transport ,Neuron ,Neuroscience ,Neurotrophin - Abstract
The role of neurotrophins as target-derived proteins that promote neuron survival following their retrograde transport from the terminals to the cell bodies of neurons has been firmly established in the developing peripheral nervous system. However, neurotrophins appear to have more diverse functions, particularly in the adult central nervous system. Brain-derived neurotrophic factor (BDNF), for example, produces a variety of neuromodulatory effects in the brain that are more consistent with local actions than with long-distance retrograde signalling. Here we show that BDNF is widely distributed in nerve terminals, even in brain areas such as the striatum that lack BDNF messenger RNA, and that inhibition of axonal transport or deafferentation depletes BDNF. The number of striatal neurons that contain the calcium-binding protein parvalbumin was decreased in BDNF+/- and BDNF-/- mice in direct proportion to the loss of BDNF protein, which is consistent with anterogradely supplied BDNF having a functional role in development or maintenance. Thus the anterograde transport of BDNF from neuron cell bodies to their terminals may be important for the trafficking of BDNF in the brain.
- Published
- 1997
10. Isolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning
- Author
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Samuel Davis, Maisonpierre Peter C, Joanne Bruno, Ann Acheson, George D. Yancopoulos, Terence E Ryan, Vivek Jain, Czeslaw Radziejewski, Aldrich Thomas H, Pamela F. Jones, and Debra L Compton
- Subjects
Molecular Sequence Data ,Neovascularization, Physiologic ,Protein tyrosine phosphatase ,Biology ,Ligands ,Tropomyosin receptor kinase C ,Protein Structure, Secondary ,General Biochemistry, Genetics and Molecular Biology ,Receptor tyrosine kinase ,TIE1 ,Mice ,chemistry.chemical_compound ,Angiopoietin-1 ,Animals ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Phosphotyrosine ,In Situ Hybridization ,Glycoproteins ,Membrane Glycoproteins ,Sequence Homology, Amino Acid ,Biochemistry, Genetics and Molecular Biology(all) ,Gene Expression Regulation, Developmental ,Proteins ,Heart ,Tyrosine phosphorylation ,Protein-Tyrosine Kinases ,Receptor, TIE-2 ,Molecular biology ,Rats ,Cell biology ,Vascular endothelial growth factor A ,chemistry ,embryonic structures ,ROR1 ,cardiovascular system ,biology.protein ,Cattle ,Endothelium, Vascular ,Peptides ,Sequence Alignment ,Tyrosine kinase ,Cell Division ,Signal Transduction - Abstract
TIE2 is a receptor-like tyrosine kinase expressed almost exclusively in endothelial cells and early hemopoietic cells and required for the normal development of vascular structures during embryogenesis. We report the identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a novel expression cloning technique that involves intracellular trapping and detection of the ligand in COS cells. The structure of Angiopoietin-1 differs from that of known angiogenic factors or other ligands for receptor tyrosine kinases. Although Angiopoietin-1 binds and induces the tyrosine phosphorylation of TIE2, it does not directly promote the growth of cultured endothelial cells. However, its expression in close proximity with developing blood vessels implicates Angiopoietin-1 in endothelial developmental processes.
- Published
- 1996
11. Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth
- Author
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Li Pan, Richard Vejsada, Thomas M. DeChiara, Ann Acheson, Chitra Suri, Nancy Y. Ip, Beth Friedman, Ann Kato, Joyce McClain, Neil Stahl, George D. Yancopoulos, Joanne C. Conover, and William Poueymirou
- Subjects
Central Nervous System ,Cell Survival ,Cell Count ,Nerve Tissue Proteins ,Receptors, Nerve Growth Factor ,Gene mutation ,Ciliary neurotrophic factor ,Ligands ,Efferent Pathways ,General Biochemistry, Genetics and Molecular Biology ,Mice ,medicine ,Animals ,Ciliary Neurotrophic Factor ,Nerve Growth Factors ,Receptor ,Receptor, Ciliary Neurotrophic Factor ,Motor Neurons ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,Embryo ,Motor neuron ,Mice, Mutant Strains ,medicine.anatomical_structure ,Spinal Cord ,Immunology ,biology.protein ,Genes, Lethal ,CLCF1 ,Ciliary neurotrophic factor receptor ,Neuroscience ,Brain Stem ,Neurotrophin - Abstract
Ciliary neurotrophic factor (CNTF) supports motor neuron survival in vitro and in mouse models of motor neuron degeneration and was considered a candidate for the muscle-derived neurotrophic activity that regulates motor neuron survival during development. However, CNTF expression is very low in the embryo, and CNTF gene mutations in mice or human do not result in notable abnormalities of the developing nervous system. We have generated and directly compared mice containing null mutations in the genes encoding CNTF or its receptor (CNTFR alpha). Unlike mice lacking CNTF, mice lacking CNTFR alpha die perinatally and display severe motor neuron deficits. Thus, CNTFR alpha is critical for the developing nervous system, most likely by serving as a receptor for a second, developmentally important, CNTF-like ligand.
- Published
- 1995
12. Diverse roles of neurotrophic factors in health and disease
- Author
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Ronald M. Lindsay and Ann Acheson
- Subjects
Nervous system ,biology ,General Neuroscience ,Regeneration (biology) ,Growth factor ,medicine.medical_treatment ,Context (language use) ,Ciliary neurotrophic factor ,medicine.anatomical_structure ,nervous system ,Neurotrophic factors ,Glial cell line-derived neurotrophic factor ,biology.protein ,medicine ,Neuroscience ,Neurotrophin - Abstract
Neurotrophic factors constitute a class of molecules that are now considered critical for the development, maintenance and regeneration of the nervous system. Much of the conceptual framework surrounding the suspected function of neurotrophic factors has emerged from studies of the prototypical neurotrophic factor—nerve growth factor (NGF). In this review we will compare established properties of NGF with recent studies on the biology of brain-derived neurotrophic factor (BDNF), an NGF-related neurotrophin, and an unrelated factor, ciliary neurotrophic factor (CNTF), not only in the context of the diverse roles of these factors in nervous system development and maintenance but also in terms of the therapeutic potential of neurotrophic factors.
- Published
- 1994
13. Characterization and crystallization of recombinant human neurotrophin-4
- Author
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N. J. Tobkes, Nikos Panayotatos, Terence E Ryan, Wayne A. Hendrickson, James P. Fandl, Ann Acheson, N. Q. Mcdonald, H. Cudny, and Somesh Nigam
- Subjects
biology ,Growth factor ,medicine.medical_treatment ,Biological activity ,Cell Biology ,biology.organism_classification ,medicine.disease_cause ,Biochemistry ,Embryonic stem cell ,Enterobacteriaceae ,law.invention ,nervous system ,law ,medicine ,Recombinant DNA ,biology.protein ,Molecular Biology ,Escherichia coli ,Bacteria ,Neurotrophin - Abstract
Neurotrophin-4 (NT-4) is the most recently discovered member of the neurotrophin family. We have expressed, refolded, and purified recombinant human NT-4 from Escherichia coli and compared it with recombinant human NT-4 secreted into the culture medium of baculovirus-infected insect cells. Both preparations were characterized and determined to be indistinguishable according to several biochemical criteria. Recombinant NT-4 from E. coli was crystallized in a form suitable for x-ray analysis, and characterization of these crystals indicated that NT-4 was present as a dimer within the asymmetric unit. NT-4 was active in promoting the survival of rat TrkB receptor-expressing fibroblasts, but was inactive on embryonic chicken sensory neurons, unlike the other members of the neurotrophin family and in contrast to the reported activities of partially purified NT-4.
- Published
- 1994
14. Immunological relationships of NGF, BDNF, and NT-3: recognition and functional inhibition by antibodies to NGF
- Author
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RA Murphy, Robert S. Hodges, RF Alderson, Julie Haskins, Carl D. Richards, Vera Chlumecky, Ann Acheson, Philip A. Barker, RM Lindsay, and E Reklow
- Subjects
Cell Survival ,Blotting, Western ,Molecular Sequence Data ,Nerve Tissue Proteins ,Chick Embryo ,Neurotrophin-3 ,PC12 Cells ,Antibodies ,law.invention ,Mice ,Neurotrophin 3 ,Neurotrophic factors ,law ,Ganglia, Spinal ,Neurites ,Animals ,Humans ,Amino Acid Sequence ,Nerve Growth Factors ,RNA, Messenger ,Cells, Cultured ,Neurons ,Brain-derived neurotrophic factor ,Ganglia, Sympathetic ,Sequence Homology, Amino Acid ,biology ,Brain-Derived Neurotrophic Factor ,General Neuroscience ,Articles ,Molecular biology ,Peptide Fragments ,Recombinant Proteins ,Blot ,Nerve growth factor ,nervous system ,Polyclonal antibodies ,Immunology ,biology.protein ,Recombinant DNA ,Neurotrophin - Abstract
Polyclonal antibodies raised against mouse 2.5S NGF (mNGF) and against synthetic peptides made from hydrophilic portions of mNGF have been used to compare the immunological properties of mNGF, human recombinant brain-derived neurotrophic factor (hrBDNF), and human recombinant neurotrophin-3 (hrNT-3). Affinity-isolated antibodies raised against intact mNGF reacted with all three neurotrophins when tested by ELISA and totally or partially blocked the bioactivities of the proteins in survival assays of embryonic chicken sensory and sympathetic neurons. On Western blots, mNGF antibodies reacted with all three neurotrophins but less well with hrBDNF and hrNT-3 than with mNGF. Antibodies to hydrophilic peptides within NGF (amino acids 23–35, 59–67, 69–79, and 91–100) showed partial reactivity with some but not all of the neurotrophins when tested by ELISA and on Western blots. The peptide antibodies were also selectively effective in reducing the survival- promoting activity of the neurotrophins on sensory neurons. Results show that mNGF, hrBDNF, and hrNT-3 are immunologically related proteins and that mNGF antibodies react also with other members of the neurotrophin family.
- Published
- 1993
15. Cholinergic differentiation of rat sympathetic neurons in culture: Effects of factors applied to distal neurites
- Author
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Daren R. Ure, Ann Acheson, and Robert B. Campenot
- Subjects
medicine.medical_specialty ,Sympathetic Nervous System ,Tyrosine 3-Monooxygenase ,Neurite ,Biology ,Leukemia Inhibitory Factor ,Choline O-Acetyltransferase ,Rats, Sprague-Dawley ,Internal medicine ,Neurites ,medicine ,Animals ,Cholinergic neuron ,Molecular Biology ,Cells, Cultured ,Neurons ,Axon Fasciculation ,Lymphokines ,Tyrosine hydroxylase ,Interleukin-6 ,Cell Differentiation ,Cell Biology ,Growth Inhibitors ,Rats ,Cell biology ,Endocrinology ,Nerve growth factor ,nervous system ,Cell culture ,Culture Media, Conditioned ,Enzyme Induction ,Cholinergic ,Leukemia inhibitory factor ,Developmental Biology - Abstract
Cholinergic properties are induced in sympathetic neurons by several factors applied to entire neurons in culture. Evidence from work with the rat sweat gland model indicates that factors located in target tissues can induce cholinergic differentiation in vivo. We now report that when leukemia inhibitory factor (LIF), heart cell-conditioned medium (HCCM), or dermal fibroblast-conditioned medium (DFCM) is applied to only distal neurites in compartmented cultures of rat sympathetic neurons, the neurons exhibit an increase in specific choline acetyltransferase activity and a concomitant decrease in levels of tyrosine hydroxylase. LIF, HCCM, and DFCM also induce neurite fasciculation, thus suggesting an additional role of cholinergic switching factors in regulating axon-axon and/or axon-substrate adhesion. These results demonstrate that rat sympathetic neurons have the cellular machinery to respond to cholinergic differentiation cues located in peripheral targets, analogous to the response to nerve growth factor.
- Published
- 1992
16. Spatiotemporal increases in epidermal growth factor receptors following peripheral nerve injury
- Author
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Jean G. Toma, Philip A. Barker, T.C. Mathew, S Pareek, RA Murphy, Ann Acheson, and Freda D. Miller
- Subjects
medicine.medical_specialty ,Time Factors ,Immunocytochemistry ,In situ hybridization ,Biology ,Myelin ,Epidermal growth factor ,Skin Physiological Phenomena ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Receptor ,Cells, Cultured ,General Neuroscience ,Rats, Inbred Strains ,RNA Probes ,Articles ,Fibroblasts ,Nerve injury ,Blotting, Northern ,Immunohistochemistry ,Sciatic Nerve ,Rats ,Cell biology ,ErbB Receptors ,Antisense Elements (Genetics) ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Immunoglobulin G ,Peripheral nerve injury ,RNA ,Female ,Schwann Cells ,Sciatic nerve ,medicine.symptom ,Myelin P0 Protein ,Myelin Proteins - Abstract
Non-neuronal cells of peripheral nerve respond to axonal injury with a series of cellular changes that facilitate neuronal regeneration. To characterize the potential role of the epidermal growth factor (EGF) family of proteins in this response, we monitored the expression of EGF receptor mRNA and protein in the injured rat sciatic nerve. EGF receptor mRNA is synthesized in both primary cultured fibroblasts and Schwann cells, and Schwann cells express EGF receptor-like immunoreactivity. In situ hybridization and immunocytochemistry revealed that EGF receptor mRNA and protein are expressed in Schwann cells and fibroblasts of the sciatic nerve in vivo, and that receptor levels increase following nerve injury. Thirty-six hours postlesion, EGF receptors were expressed in gradients along the nerve both proximal and distal to the lesion, with the highest levels localized adjacent to the transection site. By 72 hr, receptor levels were maintained in a gradient in the proximal segment, but were uniformly increased throughout the portions of the distal segment that were analyzed. These changes were similar to those observed for low-affinity NGF receptor mRNA and protein, with transection causing increased expression in both Schwann cells and fibroblasts. Northern blots confirmed that primary cultured fibroblasts express low-affinity NGF receptor mRNA. To determine whether spatiotemporal gradients were a general characteristic of the nerve injury response, we monitored expression of the mRNA encoding the major myelin protein P0. Levels of P0 mRNA decreased initially in cells immediately adjacent to the transection site and, by 72 hr, were uniformly decreased throughout the distal segment. These data suggest that members of the EGF family of proteins may play a role in the peripheral nerve response to injury, and demonstrate a generalized gradient of cellular responses that commence at the transection site and progress distally in the nerve in the absence of intact axons.
- Published
- 1992
17. Nerve Growth Factor
- Author
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Ann Acheson, Hans Thoenen, Rolf Heumann, and Sigrun I. Korsching
- Subjects
Exocrine gland ,biology ,Chemistry ,Growth factor ,medicine.medical_treatment ,Molecular cloning ,Cell biology ,Nerve growth factor ,medicine.anatomical_structure ,nervous system ,Mitogen-activated protein kinase ,medicine ,biology.protein ,Peptide sequence ,Function (biology) ,Neurotrophin - Abstract
In contrast to all other molecules which are labelled 'growth factor', NGF is not a mitogen. It is a neurotrophic molecule essential for the development and maintenance of function of specific populations of peripheral and possibly also central neurons. The availability of NGF in large quantities from exocrine glands (e.g. male mouse submandibular gland), where NGF does not play a neurotrophic role, has allowed the purification of NGF, the production of specific antibodies, the determination of its amino acid sequence and finally the molecular cloning of NGF leading to the elucidation of its precursor structure and its genomic organization. Comparison of the biological activities and the immunological properties of NGF isolated from different sources demonstrated that the active centre of the molecule has been highly conserved during evolution, whereas other parts of the molecule determining immunological properties have undergone considerable changes. After a survey of the essential biological actions of NGF, this paper concentrates on two actual questions of NGF research, namely the regulation of NGF synthesis in the target tissues of NGF-responsive neurons, and the molecular mechanism(s) of action of NGF on these neurons.
- Published
- 2008
18. Fuels planning: science synthesis and integration; environmental consequences fact sheet 11: Smoke Impact Spreadsheet (SIS) model
- Author
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Ann Acheson and Trent Wickman
- Subjects
Smoke ,Fact sheet ,Environmental science ,Environmental economics - Published
- 2005
19. The Role of Cell Adhesion Molecules in Neurite Growth
- Author
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Ann Acheson and Daren R. Ure
- Subjects
Neurite growth ,Chemistry ,Cell adhesion molecule ,Nectin ,Biophysics ,Neural cell adhesion molecule - Published
- 2003
20. National strategic plan: modeling and data systems for wildland fire and air quality
- Author
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David V. Sandberg, Colin C. Hardy, Roger D. Ottmar, J.A. Kendall Snell, Ann Acheson, Janice L. Peterson, Paula Seamon, Peter Lahm, and Dale. Wade
- Published
- 1999
21. An assessment of the effects of human-caused air pollution on resources within the interior Columbia River basin
- Author
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Robert G. Amundson, Kathy A. Tonnessen, John T. Turk, Anna W. Schoettle, John Vimont, Ann Acheson, and Janice L. Peterson
- Subjects
Hydrology ,geography ,geography.geographical_feature_category ,Air pollution ,medicine ,Drainage basin ,Environmental science ,Acid rain ,Visibility ,medicine.disease_cause - Published
- 1999
22. Antiangiogenic gene therapy targeting the endothelium-specific receptor tyrosine kinase Tie2
- Author
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Laura P. Hale, Czeslaw Radziejewski, Kevin G. Peters, Samuel E. George, Jake A. Buxton, Mark W. Dewhirst, George D. Yancopoulos, Maisonpierre Peter C, Ann Acheson, Keith M. Channon, and Pengnian Lin
- Subjects
Angiogenesis ,Genetic enhancement ,Melanoma, Experimental ,Receptor tyrosine kinase ,Metastasis ,Viral vector ,Adenoviridae ,Neovascularization ,Angiopoietin-2 ,Mice ,medicine ,Angiopoietin-1 ,Tumor Cells, Cultured ,Animals ,Humans ,Neoplasm Metastasis ,Phosphorylation ,Mice, Inbred BALB C ,Multidisciplinary ,Membrane Glycoproteins ,biology ,Neovascularization, Pathologic ,Melanoma ,Proteins ,Receptor Protein-Tyrosine Kinases ,Genetic Therapy ,Biological Sciences ,medicine.disease ,Angiopoietin receptor ,Receptor, TIE-2 ,Rats ,Cancer research ,biology.protein ,Female ,Endothelium, Vascular ,medicine.symptom - Abstract
Angiogenesis is required for tumor growth and metastasis, and inhibition of angiogenesis is a promising approach for anticancer therapy. Tie2 (a.k.a Tek) is an endothelium-specific receptor tyrosine kinase known to play a role in tumor angiogenesis. To explore the therapeutic potential of blocking the Tie2 pathway, an adenoviral vector was constructed to deliver a recombinant, soluble Tie2 receptor (AdExTek) capable of blocking Tie2 activation. Two days after i.v. injection of AdExTek, the plasma concentration of ExTek exceeded 1 mg/ml and was maintained for about 8 days. Administration of AdExTek to mice with two different well established primary tumors, a murine mammary carcinoma (4T1) or a murine melanoma (B16F10.9), significantly inhibited the growth rate of both tumors (64% and 47%, respectively). To study the effect of ExTek on tumor metastasis, both tumor cell lines were coinjected i.v. with either AdExTek or a control virus. Mice coinjected with control virus developed numerous large, well vascularized lung metastases. In contrast, mice coinjected with AdExTek virus developed few, if any, grossly apparent metastases, and histologic examination revealed only small avascular clusters of tumor cells. Administration of AdExTek also inhibited tumor metastasis when delivered at the time of surgical excision of primary tumors in a clinically relevant model of tumor metastasis. This study demonstrates the potential utility of gene therapy for systemic delivery of an antiangiogenic agent targeting an endothelium-specific receptor, Tie2.
- Published
- 1998
23. Synergistic but transient rescue effects of BDNF and GDNF on axotomized neonatal motoneurons
- Author
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Ronald M. Lindsay, J.L Tseng, A.C Kato, Patrick Aebischer, R Vejsada, and Ann Acheson
- Subjects
Programmed cell death ,Time Factors ,medicine.medical_treatment ,Nerve Tissue Proteins ,Ciliary neurotrophic factor ,Pharmacology ,Rats, Sprague-Dawley ,Neurotrophic factors ,In vivo ,medicine ,Glial cell line-derived neurotrophic factor ,Animals ,Glial Cell Line-Derived Neurotrophic Factor ,Nerve Growth Factors ,Brain-derived neurotrophic factor ,Motor Neurons ,biology ,Dose-Response Relationship, Drug ,General Neuroscience ,Brain-Derived Neurotrophic Factor ,Axotomy ,Drug Synergism ,Rats ,Drug Combinations ,nervous system ,Animals, Newborn ,biology.protein ,Sciatic nerve ,Neuroscience - Abstract
Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), members of distinct families of polypeptide growth factors, have been shown to support motoneurons under various in vitro and in vivo conditions. We used a model of motoneuron cell death induced by sciatic nerve section in newborn rats and compared the efficacy of BDNF and GDNF administered alone or simultaneously in order to determine whether combinations of neurotrophic proteins can produce more potent motoneuron rescue than individual factors. The factors were administered by different methods, including (i) a single dose on to the transected nerve, (ii) continuous delivery from implanted slow-release polymer rods (BDNF) or encapsulated cells (GDNF), and (iii) repeated systemic injections (BDNF). Irrespective of the method of administration, either factor alone produced rescue effects which dramatically declined at two weeks as compared to one week post-lesion. In contrast, this decrease was significantly reduced when BDNF and GDNF were used simultaneously provided that one factor was applied on to the nerve while the other was continuously released from the rods or capsules. Other combinations in which GDNF was replaced by ciliary neurotrophic factor or axokine-1 failed to reproduce such additive activity. Two conclusions can be made from these experiments. First, when BDNF and GDNF are administered simultaneously but by distinct routes of delivery, their survival-promoting effects on the injured developing motoneurons are potentiated; second, even continuous delivery of each of these trophic factors alone cannot completely abrogate the time-dependent decline in rescue effects in this model of motoneuron cell death.
- Published
- 1998
24. BDNF attenuates functional and structural disorders in nerves of galactose-fed rats
- Author
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Maryanne Bache, Ann Acheson, Nigel A. Calcutt, Ronald M. Lindsay, Peter S. DiStefano, and Andrew P. Mizisin
- Subjects
medicine.medical_specialty ,Neural Conduction ,Motor nerve ,Nerve Fibers, Myelinated ,Nerve conduction velocity ,Pathology and Forensic Medicine ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Myelin ,Aldehyde Reductase ,Internal medicine ,medicine ,Reaction Time ,Animals ,Neurons, Afferent ,Axon ,Enzyme Inhibitors ,Muscle, Skeletal ,Brain-derived neurotrophic factor ,Motor Neurons ,Chemistry ,Brain-Derived Neurotrophic Factor ,Galactose ,Peripheral Nervous System Diseases ,General Medicine ,medicine.disease ,Sciatic Nerve ,Rats ,medicine.anatomical_structure ,Endocrinology ,Nerve growth factor ,Peripheral neuropathy ,nervous system ,Neurology ,Female ,Neurology (clinical) ,Sciatic nerve ,Spinal Nerve Roots ,Neuroscience - Abstract
Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR). Galactose-fed rats develop a neuropathy characterized by nerve conduction deficits and axonal atrophy. To investigate the possibility that galactose metabolism by AR influences axonal function and structure by altering production of neurotrophic factors, the impact of galactose intoxication on nerve and muscle BDNF levels and the effects of exogenous BDNF treatment on galactose neuropathy were examined using biochemical, electrophysiologic and morphometric techniques. Galactose feeding increased BDNF protein in peripheral nerve and muscle. Exogenous BDNF treatment attenuated motor nerve conduction velocity deficits in the sciatic nerve of galactose-fed animals and myelin splitting of motor axons in the ventral root. In contrast, sensory nerve conduction velocity (SNCV) deficits in the sciatic nerve and myelin splitting in the central projections of sensory neurons were not prevented by BDNF treatment. BDNF treatment did not attenuate reduced axonal caliber in the sciatic nerve, but did ameliorate the diminution of the caliber of central sensory projections in the dorsal root. These findings point to the potential use of BDNF in the treatment of peripheral neuropathies.
- Published
- 1997
25. Aldose reductase inhibition increases CNTF-like bioactivity and protein in sciatic nerves from galactose-fed and normal rats
- Author
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Andrew P. Mizisin, Frank M. Longo, Ann Acheson, Nigel A. Calcutt, and Peter S. DiStefano
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Enzyme-Linked Immunosorbent Assay ,Nerve Tissue Proteins ,Ciliary neurotrophic factor ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Polyol pathway ,Aldehyde Reductase ,Internal medicine ,Gene expression ,Internal Medicine ,medicine ,Animals ,Ciliary Neurotrophic Factor ,Nerve Growth Factors ,RNA, Messenger ,Enzyme Inhibitors ,Aldose reductase ,biology ,Galactose ,Blotting, Northern ,Aldose reductase inhibitor ,Sciatic Nerve ,Rats ,Endocrinology ,chemistry ,biology.protein ,Phthalazines ,Biological Assay ,Female ,Sciatic nerve ,medicine.drug ,Neurotrophin - Abstract
The impact of exaggerated polyol pathway flux on ciliary neurotrophic factor (CNTF)-like bioactivity and expression of CNTF in rat sciatic nerve was examined after 2 months of galactose intoxication. Polyol content was elevated (P < 0.001) and motor nerve conduction velocity reduced (P < 0.05) in galactose-fed rats compared with control animals or control and galactose-fed rats treated with the aldose reductase inhibitor (ARI) Ponalrestat. CNTF-like bioactivity in the galactose-fed group was reduced to 30% of that assayed in the control group (P < 0.001). ARI treatment significantly increased CNTF-like bioactivity by 60% compared with the untreated galactose group (P < 0.05) but did not restore it to control levels. Unexpectedly, bioactivity in ARI-treated control animals was increased by nearly 250% compared with untreated controls (P < 0.005). In addition to the deficit in CNTF bioactivity in untreated galactose rats, the expression of protein, but not of mRNA, was reduced (P < 0.05). In ARI-treated control and galactose-fed rats, the expression of CNTF peptide was significantly enhanced above control levels (both P < 0.05). Concomitant with the reduction in CNTF levels, there was a shift in the axonal size-frequency distribution of myelinated fibers toward smaller axons in galactose-fed rats that was prevented by ARI treatment. Since galactose feeding has little impact on levels of CNTF mRNA, these observations suggest that deficits in CNTF-like bioactivity may result from a posttranscriptional modification of neurotrophic protein expression or turnover. Unlike other functional and structural disorders in galactose neuropathy, factors other than polyol accumulation may contribute to the deficit in CNTF-like bioactivity.
- Published
- 1997
26. Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines
- Author
-
Wayne A. Hendrickson, Anu Thadani, Robert Somogyi, Nikos Panayotatos, Elzbieta Radziejewska, Neil Q. McDonald, and Ann Acheson
- Subjects
Stereochemistry ,Leukemia inhibitory factor receptor ,Nerve Tissue Proteins ,Receptors, Nerve Growth Factor ,Ciliary neurotrophic factor ,Biochemistry ,Leukemia Inhibitory Factor ,Epitope ,Protein Structure, Secondary ,Epitopes ,Animals ,Humans ,Ciliary Neurotrophic Factor ,Binding site ,Receptor ,Molecular Biology ,Receptor, Ciliary Neurotrophic Factor ,chemistry.chemical_classification ,Lymphokines ,Binding Sites ,Linear epitope ,biology ,Interleukin-6 ,Cell Biology ,Glycoprotein 130 ,Growth Inhibitors ,Cell biology ,Amino acid ,chemistry ,Growth Hormone ,biology.protein ,Cytokines ,Chickens - Abstract
By rational mutagenesis, receptor-specific functional analysis, and visualization of complex formation in solution, we identified individual amino acid side chains involved specifically in the interaction of ciliary neurotrophic factor (CNTF) with CNTFR alpha and not with the beta-components, gp130 and LIFR. In the crystal structure, the side chains of these residues, which are located in helix A, the AB loop, helix B, and helix D, are surface accessible and are clustered in space, thus constituting an epitope for CNTFR alpha. By the same analysis, a partial epitope for gp130 was also identified on the surface of helix A that faces away from the alpha-epitope. Superposition of the CNTF and growth hormone structures showed that the location of these epitopes on CNTF is analogous to the location of the first and second receptor epitopes on the surface of growth hormone. Further comparison with proposed binding sites for alpha- and beta-receptors on interleukin-6 and leukemia inhibitory factor indicated that this epitope topology is conserved among helical cytokines. In each case, epitope I is utilized by the specificity-conferring component, whereas epitopes II and III are used by accessory components. Thus, in addition to a common fold, helical cytokines share a conserved order of receptor epitopes that is function related.
- Published
- 1995
27. A BDNF autocrine loop in adult sensory neurons prevents cell death
- Author
-
James P. Fandl, George D. Yancopoulos, Anu Thadani, Joanne C. Conover, Thomas M. DeChiara, Stephen P. Squinto, Ann Acheson, Ronald M. Lindsay, and Michelle Russell
- Subjects
Programmed cell death ,Aging ,medicine.medical_treatment ,Nerve Tissue Proteins ,Biology ,Mice ,Dorsal root ganglion ,Neurotrophic factors ,Polysaccharides ,Ganglia, Spinal ,medicine ,Animals ,Neurons, Afferent ,RNA, Messenger ,Autocrine signalling ,Cells, Cultured ,Brain-derived neurotrophic factor ,Messenger RNA ,Multidisciplinary ,Cell Death ,Growth factor ,Brain-Derived Neurotrophic Factor ,Anatomy ,Oligonucleotides, Antisense ,Sensory neuron ,Cell biology ,medicine.anatomical_structure ,nervous system - Abstract
During the initial phase of their development, sensory neurons of the dorsal root ganglion (DRG) require target-derived trophic support for their survival, but as they mature they lose this requirement. Because many of these neurons express BDNF (brain-derived neurotrophic factor) messenger RNA, we hypothesized that BDNF might act as an autocrine survival factor in adult DRG neurons, thus explaining their lack of dependence on exogenous growth factors. When cultured adult DRG cells were treated with antisense oligonucleotides to BDNF, expression of BDNF protein was reduced by 80%, and neuronal survival was reduced by 35%. These neurons could be rescued by exogenous BDNF or neurotrophin-3, but not by other growth factors. Similar results were obtained with single-neuron microcultures, whereas microcultures derived from mutant mice lacking BDNF were unaffected by antisense oligonucleotides. Our results strongly support an autocrine role for BDNF in mediating the survival of a subpopulation of adult DRG neurons.
- Published
- 1995
28. Exchange of a single amino acid interconverts the specific activity and gel mobility of human and rat ciliary neurotrophic factors
- Author
-
Vivien Wong, Ann Acheson, Nikos Panayotatos, Denise Pearsall, Anu Thadani, and Elzbieta Radziejewska
- Subjects
Arginine ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Nerve Tissue Proteins ,Receptors, Cell Surface ,Chick Embryo ,Biology ,Ciliary neurotrophic factor ,Protein Engineering ,Biochemistry ,Binding, Competitive ,Polymerase Chain Reaction ,Protein Structure, Secondary ,Structure-Activity Relationship ,Neurotrophic factors ,Animals ,Humans ,Amino Acid Sequence ,Ciliary Neurotrophic Factor ,Nerve Growth Factors ,Receptor ,Molecular Biology ,Receptor, Ciliary Neurotrophic Factor ,Alanine ,Base Sequence ,Biological activity ,Cell Biology ,Fusion protein ,Rats ,Glutamine ,biology.protein ,Electrophoresis, Polyacrylamide Gel - Abstract
Human and rat ciliary neurotrophic factors (CNTF), which share 85% sequence identity, promote the survival of chicken embryo ciliary ganglia neurons in vitro, but display a 4-5-fold difference in specific activity. To explore the origin of this difference and gain insight into the structural organization of CNTF, we created chimeric proteins of these two species. Surprisingly, we found that the differences in two apparently unrelated properties, gel mobility and specific activity, resided in a single amino acid. Substituting arginine residue 63 of rat CNTF into the human sequence created a protein with the properties of rat CNTF. Conversely, substituting the human CNTF glutamine residue 63 into rat CNTF generated a protein with the properties of human CNTF. Binding experiments confirmed that the distinct specific activities of human and rat CNTF and their chimeras reside in structural differences among these ligands rather than species differences in their receptors. Alanine substitution (Q63A) had no effect on the properties of human CNTF, whereas the R63A substitution reduced both the gel mobility and the specific activity of rat CNTF. Finally, a Q95R substitution at a different position of human CNTF had no effect on its properties. These results demonstrate that Arg-63 is both specific and critical in determining the structural differences of human and rat CNTF.
- Published
- 1993
29. Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: inhibition by antibodies to NGF
- Author
-
Ralph F. Alderson, RA Murphy, Ann Acheson, Philip A. Barker, and Freda D. Miller
- Subjects
Cell Survival ,Blotting, Western ,Schwann cell ,Nerve Tissue Proteins ,Chick Embryo ,Biology ,Antibodies ,Mice ,Neurotrophic factors ,medicine ,Animals ,Nerve Growth Factors ,Neurons, Afferent ,RNA, Messenger ,Fibroblast ,Cells, Cultured ,Brain-derived neurotrophic factor ,General Neuroscience ,Brain-Derived Neurotrophic Factor ,Brain ,Fibroblasts ,Sensory neuron ,Axons ,Cell biology ,Culture Media ,Rats ,medicine.anatomical_structure ,Nerve growth factor ,nervous system ,Cell culture ,Immunology ,Neuroglia ,Schwann Cells - Abstract
mRNA coding for brain-derived neurotrophic factor (BDNF) has been detected in cultured L929 fibroblasts, rat dermal fibroblasts, and sciatic nerve Schwann cells, as well as in rat skin. Medium conditioned by cultured fibroblasts and Schwann cells also stimulates neurite growth from retinal explants and promotes the survival in culture of BDNF-responsive sensory neurons; biological activity is abolished by antibodies raised against NGF. These results suggest that molecules with BDNF-like activity may be produced by cells in the peripheral nervous system and that the BDNF-like activity in fibroblasts and Schwann cells is derived from molecules immunologically related to NGF. In support of this concept, antibodies against NGF have been found to reduce the biological activity of recombinant BDNF in culture and to cross-react with BDNF on Western blots.
- Published
- 1991
30. Cell and tissue culture laboratory procedures
- Author
-
Ann Acheson
- Subjects
Tissue culture ,Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Cell ,medicine ,Cell Biology ,Biology - Published
- 1994
31. Nerve growth factor-mediated enzyme induction in primary cultures of bovine adrenal chromaffin cells: specificity and level of regulation
- Author
-
Ann Acheson, Hans Thoenen, and Kurt Naujoks
- Subjects
medicine.medical_specialty ,Tyrosine 3-Monooxygenase ,Population ,Dopamine beta-Hydroxylase ,Biology ,chemistry.chemical_compound ,Internal medicine ,Adrenal Glands ,Cyclic AMP ,medicine ,Animals ,Nerve Growth Factors ,Enzyme inducer ,education ,Cells, Cultured ,education.field_of_study ,Tyrosine hydroxylase ,Phenylethanolamine N-Methyltransferase ,General Neuroscience ,Articles ,Acetylcholinesterase ,Phenylethanolamine N-methyltransferase ,Nerve growth factor ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Chromaffin System ,Chromaffin cell ,Dopa Decarboxylase ,biology.protein ,Cattle ,Acetylcholine ,medicine.drug - Abstract
Primary cultures of bovine adrenal chromaffin cells provide large quantities of a homogeneous population of target cells for nerve growth factor (NGF) and, thus, are a suitable system for studying the molecular mechanism of action of NGF. In this study, we have shown that NGF mediates the specific induction of the key enzymes in catecholamine biosynthesis, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT). Acetylcholinesterase (AChE), an enzyme which catalyzes the breakdown of acetylcholine, is also induced by NGF. We have compared NGF-mediated TH and AChE induction and have provided pharmacological evidence that TH induction involves a post-transcriptional, polyadenylation-dependent event (blockable by 9-beta-arabinofuranosyladenine but not by alpha- amanitin), whereas AChE induction requires transcription (blockable by alpha-amanitin). DBH and PNMT appear to be regulated via the same mechanism as TH. The time course of TH induction is such that NGF must be continuously present for at least the first 36 hr (during which time TH levels remain unchanged), and then the entire increase takes place during the subsequent 12 hr. In contrast, AChE induction proceeds linearly with time of NGF exposure. These data suggest that there may be multiple mechanisms by which NGF regulates enzyme induction. We have also compared the effects of cAMP with those of NGF. As compared to NGF, cAMP produces a different pattern of enzyme induction (in addition to TH, DBH, PNMT, and AChE, dopa decarboxylase (DDC) is also induced), it acts rapidly (a 12-hr exposure produces the full effect), and it acts only at the transcriptional level (its effects are blocked by alpha-amanitin). These data provide evidence that cAMP does not act as a second messenger for NGF with regard to enzyme induction.
- Published
- 1984
32. Both Short- and Long-Term Effects of Nerve Growth Factor on Tyrosine Hydroxylase in Calf Adrenal Chromaffin Cells Are Blocked by S-Adenosylhomocysteine Hydrolase Inhibitors
- Author
-
Ann Acheson and Hans Thoenen
- Subjects
medicine.medical_specialty ,Time Factors ,Tyrosine 3-Monooxygenase ,Hydrolases ,8-Bromo Cyclic Adenosine Monophosphate ,Biology ,Methylation ,Biochemistry ,Cellular and Molecular Neuroscience ,Internal medicine ,Adrenal Glands ,Protein methylation ,medicine ,Animals ,Nerve Growth Factors ,Cells, Cultured ,L-Lactate Dehydrogenase ,Tyrosine hydroxylase ,Adenosylhomocysteinase ,Enzyme Activation ,Endocrinology ,medicine.anatomical_structure ,Nerve growth factor ,Cell culture ,Enzyme inhibitor ,Chromaffin System ,Chromaffin cell ,biology.protein ,Cattle ,Signal transduction - Abstract
We have previously shown that primary cultures of calf chromaffin cells respond to nerve growth factor (NGF) treatment with a selective induction of tyrosine hydroxylase (TH), which takes 48 h to be manifested. In the present study, we report that short exposure of calf chromaffin cells to NGF (5–60 min) results in TH activation, which involves a change in the Fmax of the enzyme with no change in the number of enzyme molecules, similar to an effect that has been previously reported in PC 12 cells. This activation is markedly potentiated when the chromaffin cells are plated on a laminin substrate, such that after 5 min of NGF exposure, there is an approximately fourfold increase in the TH activity. Both short-term activation and long-term TH induction brought about by NGF treatment are blocked by 5′-deoxy-5′-methylthioadenosine and other drugs that act as S-adenosylhomocysteine (SAH) hydrolase inhibitors to block methylation by end-product inhibition. These drugs did not inhibit cyclic AMP-mediated TH activation or increases in the levels of TH. However, measurements of the degree of blockade of methylation in cells treated with these drugs, taken together with conceptual information regarding the nonregulatory nature of methylation in eukaryotic cells, were not consistent with inhibition of methylation as the crucial effect of the drugs to block the effects of NGF. Nonetheless, since SAH hydrolase inhibitors selectively inhibited NGF-mediated effects, and not comparable effects triggered by other stimuli, these compounds provide useful tools in future studies of the biochemical signalling mechanism of NGF.
- Published
- 1987
33. Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells
- Author
-
Rupert Timpl, Ann Acheson, David Edgar, and Hans Thoenen
- Subjects
Neurite ,Tyrosine 3-Monooxygenase ,Enzyme activator ,Structure-Activity Relationship ,Laminin ,medicine ,Cell Adhesion ,Animals ,Nerve Growth Factors ,Cells, Cultured ,Aromatic L-amino acid decarboxylase ,Kidney Medulla ,biology ,Tyrosine hydroxylase ,Dose-Response Relationship, Drug ,Cell Biology ,Articles ,Molecular biology ,Peptide Fragments ,Enzyme Activation ,medicine.anatomical_structure ,Enzyme Induction ,Chromaffin cell ,biology.protein ,Catecholamine ,Immunologic Techniques ,Cattle ,Peptides ,medicine.drug - Abstract
We have investigated the effects of substrate-bound laminin on levels of enzymes of the catecholamine biosynthetic pathway in primary cultures of calf adrenal chromaffin cells. Laminin increases the levels of the enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase. This effect is selective, in that levels of other enzymes (lactate dehydrogenase, aromatic amino acid decarboxylase, and acetylcholinesterase) are not increased. The effect of laminin can be blocked by antibodies directed against a fragment of the heparin-binding domain of the molecule, whereas antibodies directed against other fragments do not block the increase in tyrosine hydroxylase. Thus the laminin domain involved in enzyme regulation in chromaffin cells is apparently the same as that previously implicated in laminin's interactions with neurons to potentiate survival and stimulate neurite outgrowth (Edgar, D., R. Timpl, and H. Thoenen, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 3:1463-1468). The increase in chromaffin cell tyrosine hydroxylase levels is preceded by an activation of the enzyme in which the Vmax (but not the Km) is altered. The effects of laminin appear to be developmentally regulated, since neither activation nor increased levels of tyrosine hydroxylase occur in adult adrenal chromaffin cells exposed to laminin.
- Published
- 1986
34. The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions
- Author
-
Urs Rutishauser, Jeffrey L. Sunshine, Dennis M. Mann, Ann Acheson, and Alison K. Hall
- Subjects
Cell signaling ,Multidisciplinary ,Membrane Glycoproteins ,Polysialic acid ,Chemistry ,Cell adhesion molecule ,Cell Membrane ,Cell Communication ,Cell biology ,Cell membrane ,medicine.anatomical_structure ,nervous system ,Cell–cell interaction ,Biochemistry ,Antigens, Surface ,medicine ,Cell Adhesion ,Sialic Acids ,Animals ,Neural cell adhesion molecule ,Cell adhesion ,Cell Adhesion Molecules ,Intracellular - Abstract
The neural cell adhesion molecule (NCAM) can influence a number of diverse intercellular events, including junctional communication, the association of axons with pathways and targets, and signals that alter levels of neurotransmitter enzymes. These pleiotropic effects appear to reflect the ability of NCAM to regulate membrane-membrane contact required to initiate specific interactions between other molecules. Such regulation can occur through changes in either NCAM expression or the molecule's content of polysialic acid (PSA). When NCAM with a low PSA content is expressed, adhesion is increased and contact-dependent events are triggered. In contrast, the large excluded volume of NCAM PSA can inhibit cell-cell interactions through hindrance of overall membrane apposition.
- Published
- 1988
35. High K+-mediated survival of spinal sensory neurons depends on developmental stage
- Author
-
Ann Acheson, Yves-Alain Barde, and Hans Thoenen
- Subjects
Neurite ,Cell Survival ,Nerve Tissue Proteins ,Chick Embryo ,Biology ,Dorsal root ganglion ,Neurotrophic factors ,Ganglia, Spinal ,medicine ,Cytotoxic T cell ,Animals ,Nerve Growth Factors ,Neurons, Afferent ,Cells, Cultured ,Brain-Derived Neurotrophic Factor ,Cell Biology ,Anatomy ,Embryonic stem cell ,Sensory neuron ,Cell biology ,Culture Media ,medicine.anatomical_structure ,Nerve growth factor ,nervous system ,Cell culture ,Potassium - Abstract
Elevated concentrations of K+ (35 mM) have previously been shown to support the survival of most embryonic chick sympathetic neurons in vitro (Wakade et al., Exp cell res 144 (1983) 377, [23]) and to be interchangeable with nerve growth factor (NGF) as a survival-promoting agent for these cells (Wakade & Thoenen, Neurosci lett 45 (1984) 71 [21]). In the present study, we show that dorsal root ganglion (DRG) neurons from embryonic day 6 do not survive in the presence of high K+, although both NGF and brain-derived neurotrophic factor (BDNF) each support the survival of more than 50% of the cells at this developmental stage. At E6, high K+ appears to have a cytotoxic effect on BDNF-dependent neurons, and there is also considerable inhibition of neurite outgrowth. At a later developmental stage (E12), high K+ supports the survival of about 40% of DRG cells. This subpopulation of neurons is distinct from that supported by NGF (as evidenced by the additivity of these two agents), but partially overlaps with that supported by BDNF (i.e., the two agents are less than additive). At E12, only approx. 20% of the cells can be supported by either NGF or BDNF, with the rest depending exclusively on one or the other of these factors. This is in contrast to the situation at E6, where there is considerable overlap between NGF- and BDNF-dependent populations.
- Published
- 1987
36. Potentiation of NGF-mediated Effects of Laminin
- Author
-
Ann Acheson and Hans Thoenen
- Subjects
Tyrosine hydroxylase ,Chemistry ,media_common.quotation_subject ,Long-term potentiation ,Cell biology ,medicine.anatomical_structure ,Nerve growth factor ,nervous system ,Cell culture ,Chromaffin cell ,medicine ,Signal transduction ,Internalization ,Receptor ,media_common - Abstract
Nerve growth factor (NGF) is a well-defined protein which is necessary for the development and maintainance of differentiated properties of peripheral sympathetic and neural crest-derived sensory neurons (for review see Thoenen et al., 1985 and refs therein). Many morphological and biochemical effects of NGF have been described in both the physiological target cells of NGF and a clonal cell line (PC12) derived from a rat pheochromocytoma. NGF is known to bind to specific cell-surface receptors, an event which is followed by internalization of the ligand-receptor complex; however, the mechanism of signal transduction after NGF’s interaction with its receptor is unknown.
- Published
- 1987
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