bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection by an ACTH4–9 analogue against the toxic effects of cisplatin and taxol on sensory neurons and glial cells in vitro
Authors: Hol E. M. , Mandys V. , Sodaar P. , Gispen W. H. , Bär P. R. 
Published: January 2005

AbstractSensory neuropathy is a serious side effect of antitumour drugs such as cisplatin and taxol. There are indications that an analogue of the adrenocorticotrophic hormone 4–9 fragment (ACTH4–9: Met(O2)‐Glu‐His‐Phe‐D‐Lys‐Phe) can prevent these neurotoxic effects. We studied the potential protective effects of this analogue in cultures of chick dorsal root ganglia and rat Schwann cells treated with cisplatin or taxol to gain insight into the mode of action and characteristics of this neuroprotection. Neurite outgrowth of sensory neurons in vitro was dose‐dependently inhibited by cisplatin and taxol; after 48 hr, 10 μg/ml cisplatin reduced outgrowth from 431 ± 17 μm to 220 ± 6 μm and 0.01 μg/ml taxol from 344 ± 3 μm to 200 ± 43 μm. Co‐treatment of 10 μg/ml cisplatin with the ACTH4–9 analogue (0.1 nM–1 nM) resulted in about 35% more outgrowth than cisplatin alone. In contrast, the analogue could not prevent taxol neurotoxicity. Migration of neurons and satellite cells from the DRG‐body is completely inhibited by 10 μg/ml cisplatin. Taxol had no effect on the migration of these cells. In addition, cisplatin was more toxic to Schwann cells than taxol; 3–10 μg/ml cisplatin significantly reduced their laminin content, total protein, 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase activity, and cell division. The ACTH4–9 analogue (0.01 nM–100 nM) had no effect on the migration of cells out of the DRGs and could not prevent the toxic effect on the Schwann cells. These data support our hypothesis that the neuroprotective effect of ACTH4–9 analogue is brought about by a direct action on neurons, possibly by replacing a Schwann‐/satellite‐cell derived trophic factor. Copyright © 1994 Wiley‐Liss, Inc.
Nerve growth factor induces the Oct‐2 transcription factor in sensory neurons with the kinetics of an immediate‐early gene
Authors: Kendall G. , Brar‐Rai A. , Ensor E. , Winter J. , Wood J. N. , Latchman D. S. 
Published: January 2005

AbstractThe Oct‐2 transcription factor has a predominantly inhibitory effect on gene expression in neuronal cell lines. This factor and its corresponding mRNA have previously been shown to be elevated in adult rat dorsal root ganglion (DRG) neurons chronically exposed to nerve growth factor (NGF). Here we show that the Oct‐2 mRNA is rapidly induced in DRG cells exposed to NGF and that such induction still occurs to a lesser extent in the presence of the protein synthesis inhibitor cycloheximide. These findings characterize Oct‐2 as a novel member of the immediate‐early class of NGF‐induced transcription factors whose previously defined members have a predominantly stimulatory effect on the expression of other genes. Induction of the Oct‐2 mRNA was also observed in DRG neurons treated with acidic fibroblast growth factor or epidermal growth factor but not with a range of other growth factors and neurotrophins. The role of the Oct‐2 transcription factor in mediating the response of DRG neurons to NGF is discussed. © 1995 Wiley‐Liss, Inc.
Altered processing of a mutant amyloid precursor protein in neuronal and endothelial cells
Authors: Zhao Boyu , Sisodia S. S. , Kusiak J. W. 
Published: January 2005

AbstractAltered proteolysis of the amyloid precursor protein (APP) may play an important role in Alzheimer disease (AD). To better understand the role of mutant APP in the pathogenesis of the disease, we stably overexpressed the mutant APP717F approximately twofold vs. the endogenous wild‐type gene in several cell types. The processing of APP was examined by Western blot analysis and immunoprecipitation. We observed distinctive patterns of APP metabolites among various cell lines. Neuronal and endothelial cells expressing mutant APP717F generated higher levels of large, potentially amyloidogenic carboxyl terminal fragments, which were enhanced upon treatment of the cells with leupeptin. These results suggest that mutations in the APP gene shift the protein processing towards the amyloidogenic pathway in neuronal and endothelial cells possibly involving the endosomal‐lysosomal system. © 1995 Wiley‐Liss, Inc.
Characterization of sialidase activity in mouse synaptic plasma membranes and its age‐related changes
Authors: Saito M. , Tanaka Y. , Tang C.‐P. , Yu R. K. , Ando S. 
Published: January 2005

AbstractSialidase activity in synaptic plasma membranes (SPM) isolated from C57BL/6 mouse brain was examined using exogenous ganglioside substrates. The enzyme activity directed toward GM3 showed sharp pH dependency with optimal pH of 4.0, and was greatly enhanced by Triton CF‐54, Nonidet P‐40 or CHAPS. The apparent Km and Vmax values for enzyme activity in SPM were 11 μM and 164 pmol/mg protein/min, respectively. Examination of sialidase activities in subcellular fractions of brain tissues showed the enrichment of enzyme activity in SPM prepared from either young adult or senescent mice. Substrate specificity of SPM sialidase was compared with that of myelin sialidase using delipidated, solubilized enzyme preparations. The SPM sialidase hydrolyzed GD1a more effectively as compared with the myelin enzyme. While SPM sialidase could hydrolyze GM1, the hydrolytic rate by the SPM enzyme was significantly lower than that by the myelin enzyme. The sialidase activity in SPM decreased with increasing age; activity was highest between the ages of 4–7 months, decreased to a relatively constant level between 13–25 months, and reached its lowest level at 31 months. These results demonstrate that SPM contain a distinct sialidase activity which is regulated in an age‐dependent manner. © 1995 Wiley‐Liss, Inc.
Endotoxin administration stimulates cerebral catecholamine release in freely moving rats as assessed by microdialysis
Authors: Lavicky J. , Dunn Adrian J. 
Published: January 2005

AbstractIn vivo microdialysis was used to measure changes in extracellular concentrations of catecholamines and indolamines in freely moving rats in response to administration of endotoxin (lipopolysaccharide, LPS). Dialysis probes were placed stereotaxically in either the medial hypothalamus or the medial prefrontal cortex. We used a repeated‐measures design in which each rat received LPS or saline, and each subject was retested with the other treatment one week later. With the dialysis probes in the medial hypothalamus, intraperitoneal (ip) administration of LPS (5 μg) increased dialysate concentrations of norepinephrine (NE, 187%), dopamine (DA, 119%), and all their measured catabolites, except normetanephrine. Dialysate concentrations of NE and DA were elevated significantly in the fourth or fifth (20 min) collection period with a peak response at around 2 hr. They returned to baseline by about 4 hr. When the dialysis probes were placed in the medial prefrontal cortex, the same dose of LPS also elevated dialysate concentrations of NE and DA, but the increases were much smaller (ca. 20%). However, a dose of 100 μg LPS increased dialysate concentrations of NE and DA from the medial prefrontal cortex to an extent comparable to that of the 5 μg dose in the hypothalamus, and the response was more prolonged. Dialysate concentrations of serotonin could not be measured reliably, but those of its catabolite, 5‐hydroxyindoleacetic acid (5‐HIAA), were also elevated in both regions. The peak of 5‐HIAA occurred at around 4 hr. Pretreatment of the rats with indomethacin (10 mg/kg ip) completely prevented the changes due to 100 μg LPS in the medial prefrontal cortex. These results support earlier neurochemical data suggesting that LPS stimulates the release of both DA and NE in the brain, and probably also release of serotonin. © 1995 Wiley‐Liss, Inc.
CNTF or (−)‐deprenyl in immature rats: Survival of axotomized facial motoneurons and weight loss
Authors: Zhang F. , Richardson P. M. , Holland D. P. , Guo Q. , Tatton William G. 
Published: January 2005

AbstractThe application of ciliary neurotrophic factor (CNTF) to the cut ends of transected facial nerves in newborn rats has been reported to reduce the death of facial motoneurons (FMns) axotomized by the transection. Systemically delivered CNTF has been found to cause cachexia in adult mice. We compared the influence of dosage of CNTF and (−)‐deprenyl on FMn death, weight loss, and animal survival in rat pups that underwent facial nerve transection at the 14th postnatal day (P14). CNTF was administered by osmotic mini‐pumps connected to tubing ending either intrathecally or extrathecally near the craniocer‐vical junction. CNTF caused weight loss and animal death that was similar to the cachexia reported in mice if administered in amounts of 1.1 μg/day or greater. At the same doses, intrathecal CNTF was more effective than extrathecal CNTF in inducing the cachexia. (−)‐Deprenyl did not alter animal survival or weight gain, even at high doses (10 mg/kg every 2 days). Intrathecal CNTF and intraperitoneal (−)‐deprenyl, but not extrathecal CNTF, significantly increased the survival of the axotomized FMns. (−)‐Deprenyl administered twice daily at 0.01 mg/kg was considerably more effective than CNTF in increasing FMn survival due to the limitation on CNTF dosage caused by the animal death. © 1995 Wiley‐Liss, Inc.
Bradykinin induces rise of free calcium in nuclei of neuroblastoma × glioma hybrid NG 108‐15 cells
Authors: Beckmann R. , Lindschau C. , Haller H. , Buchner Klaus 
Published: January 2005

AbstractConfocal fluorescence microscopy was used to study the bradykinin‐induced calcium signals in the neuro‐blastoma × glioma cell line NG 108–15. We found that bradykinin induced a rise in free calcium, not only in the cytoplasm but also in the nucleus. The nuclear and cytosolic calcium concentrations were not significantly different and rose to about 1.2 :μM. The signal was mediated by the B2‐receptor subtype as confirmed using the specific antagonist Hoe 140. Both the onset and the intensity of the calcium signals were concentration‐dependent. The rise of nuclear calcium level was independent of extracellular calcium and suppressed by thapsigargin which is known to deplete inositol 1,4,5‐trisphosphate‐sensitive calcium stores. Bradykinin‐induced calcium increase desensitizes rapidly. This desensitization was shown not to involve activation of protein kinase C. © 1995 Wiley‐Liss, Inc.
Preparation of a monoclonal antibody to a glycidic epitope of the epidermal growth factor receptor that recognizes inhibitors of astrocyte proliferation and reactive microglia
Authors: Río C. , Pérez‐Cerdá F. , Matute C. , Nieto‐Sampedro M. 
Published: January 2005

AbstractA mouse monoclonal antibody (5B9), directed against a carbohydrate epitope of human epidermal growth factor receptor (EGFR), recognized an 81‐kDalton glycoprotein in buffer‐soluble and detergent‐solubilized rat brain extracts (BE). The glycoprotein was more abundant in extracts prepared from injured brain than in those from normal tissue. Removal from BE of the antigens recognized by 5B9 increased their astrocyte mitogenic activity. Sections of injured rat brain and cultures derived from damaged brain, enriched in microglia, showed 5B9 immunoreactivity in ED1‐positive cells. The abundance of the glycoprotein recognized by 5B9 in injured, relative to normal, tissue, suggested that molecules with EGFR immunoreactivity may be expressed in reactive microglial cells and released after injury. © 1995 Wiley‐Liss, Inc.
Brain‐specific expression of human microtubule‐associated protein 1A (MAP1A) gene and its assignment to human chromosome 15
Authors: Fukuyama Ryuichi , Rapoport S. I. 
Published: January 2005

AbstractWe isolated several cDNA fragments by immunoscreening a human cDNA library with our monoclonal antibody, BG5, that showed neuronal staining on human and rat brain sections. A 1,570 bp sequence of one cDNA fragment showed 75% homology to the rat microtubule‐associated protein 1A (MAP1A) cDNA sequence. This rat MAP1A‐like human cDNA was highly specific to the adult brain among human tissues tested, and was expressed in various brain regions including white matter. The size of the mRNA detected with Northern blot analysis in adult human brain equaled 10 kb. The gene of this cDNA was assigned to human chromosome 15 that has a syntenic region of mouse chromosome 2, where the mouse MAP1A gene has been assigned. These results indicate that this rat MAP1A‐like cDNA is a portion of human MAP1A and is a conserved molecular species among humans and rodents. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
On a molecular comparison of strong and weak antagonists at the glycinergic receptor
Authors: Aprison M. H. , Galvez‐Ruano E. , Lipkowitz K. B. 
Published: January 2005

AbstractUsing molecular modeling techniques, we studied nine glycine antagonists in order to try to identify the molecular descriptors that characterize strychnine as a strong antagonist and N, N‐dimethyl‐muscimol, iso‐THIA, THIA, N‐methyl‐THIP, iso‐THAZ, THAZ, iso‐THPO, and iso‐THAO (see Experimental for chemical names) as weak glycine antagonists. We confirm that all nine compounds have the three‐atom regions (two negative and one positive) that we have postulated are necessary to permit such compounds to attach to the recognition site in the glycinergic synapse. Furthermore, in the case of antagonists we have postulated the presence of a fourth atom that can attach to the top of the chloride ion channel. Each of the nine antagonists has such a fourth negative atom and the latter property gives each of these compounds their antagonistic characteristic. Further, only in the case of strychnine is there evidence that at its positively charged end does the positive charge extend to cover a region that could bind through electrostatic domains to a tertiary carboxyl group in an amino acid like aspartate. Published molecular biological data show that such an amino acid is present in the portion of the polypeptides identified in the glycine receptor. The bidentate binding is superior to the single site attachment that is present in the other eight weak glycine antagonists. In addition, the two negative atom sites in each antagonist are also in a position to participate in electrostatic binding through bidentate involvement with the positively charged guanidinium group of arginine. The latter amino acid also has been identified in the portion of the polypeptide chain at the glycine receptor. Finally, our molecular data predict that after strychnine, the eight weak glycine antagonists listed above are in order of decreasing potency, i.e., N,N‐dimethyl‐muscimol is the best of the weak antagonists and iso‐THAO should be the weakest. © 1995 Wiley‐Liss, Inc.
Generation of cell lines from embryonic quail retina capable of mature neuronal differentiation
Authors: Pollerberg G. E. , Kuschel C. , Zenke M. 
Published: January 2005

AbstractThe avian embryonic retina is widely used as a model system for cellular and molecular studies on central nervous system neurons. We aimed at the generation of cell lines from the early embryonic quail retina by retroviral oncogene transduction. For this, we made use of the retina organ culture system which exhibits both proliferation, necessary for stable oncogene transduction, and initial neuronal differentiation, a prerequisite for the generation of cell lines with mature neuronal properties. The oncogene myc was chosen ac it is both proliferation‐inducing and differentiation‐compatible. A chimeric gene, mycER, containing v‐myc and the hormone‐binding domain of the estrogen receptor, was used for transduction in order to allow for hormone regulation of myc activity. Transduced organ‐cultured cells from temporal and nasal retina were passaged into sparse single cell cultures. From these, colonies of rapidly dividing cells were isolated and the progeny expanded as cell lines. The lines contained cells with features of neuroepithelial cells, showing vimentin and A2B5. They also contained spontaneously differentiated neuronal cells showing neurofilament L and N‐CAM18O. A subpopulation of the neuronal cells exhibited the morphological characteristics of retinal ganglion cells, i.e., large pear‐shaped somata each emitting one long process with a distinct growth cone. In addition, they showed the marker profile of retinal ganglion cells, i.e., expression of Thy‐1, G4, DMGRASP, Nr‐CAM, neurofilament H, and tau. Neuronal differentiation could be induced by the addition of db cAMP and retinoic acid. The mature neuronal features of the lines open new possibilities to study properties of retinal neurons, including ganglion cells, in a defined and manipulable experimental system. © Wiley‐Liss, Inc.
Alteration of corticotropin‐releasing factor immunoreactivity in MPTP‐treated rats
Authors: Huang C. C. , Lee E. H. Y. 
Published: January 2005

AbstractA decrease of corticotropin‐releasing factor (CRF) concentration has been reported in patients with Parkinson's disease (PD). The present study further examined the role of CRF in an animal model of parkinsonism induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Results indicated that both subchronic (2 days) and chronic (7 days) MPTP treatments decreased the number of CRF immunoreactive neurons in both the paraventricular nucleus (PVN) of the hypothalamus and the central nuelcus of the amygdala (ACN). This effect lasted for almost a month after withdrawal of chronic MPTP injections. In addition, nomifensine pretreatment protected against MPTP's toxicity on DA neurons, as assessed by tyrosine hydroxylase immunoreactivity in the substantia nigra. However, the same treatment did not prevent the toxicity of MPTP on CRF neurons. Further, no significant difference was notable in the number of CRF immunoreactive neurons between normal young adult and normal middle‐aged rats in both the PVN and the ACN. These results suggest that MPTP also produces a neurotoxicity on CRF neurons, and this effect is not secondary to MPTP's effect on DA neurons. Besides, altered CRF neuronal activity is involved in the process of pathological ageing, but not physiological ageing. Further, reduced CRF immunoreactivity in the PVN and ACN may imply alterations of neuroendocrine, autonomic as well as central functions caused by MPTP. © 1995 Wiley‐Liss, Inc.
Gangliosides have a bimodal effect on DNA synthesis in U‐1242 MG human glioma cells
Authors: Saqr H. E. , Lee M.‐C. , Burkman A. M. , Yates A. J. 
Published: January 2005

AbstractGM1, GD1a, and GT1b inhibit both PDGF‐stimulated and serum‐stimulated DNA synthesis in Swiss 3T3 cells and the human glioma cell line U‐1242 MG in a dose‐dependent manner. The ganglioside inhibitory effect is counteracted in a dose‐responsive fashion by serum such that ganglioside‐induced inhibition is essentially abolished in 10% serum. Because of the potentially important role that gangliosides play in growth regulation of human gliomas, this phenomenon was studied in detail using U‐1242 MG cells. Stimulation of DNA synthesis by low doses of serum in U‐1242 MG cells is inhibited in a dose‐responsive fashion by ganglioside GM1. However, serum itself counteracts the inhibitory effect of ganglioside in a dose responsive way. Kinetic analyses demonstrate that GM‐1 competes with some components of serum for sites on U‐1242 MG cells (Kb of GM1 =12.5 μM). On the other hand, GM1, GD1a, and GT1b stimulate DNA synthesis in quiescent U‐1242 MG cells in both sparse and confluent conditions, indicating that ganglioside‐stimulated DNA synthesis is dependent on the phase of cellular growth rather than cellular density. This growth stimulatory effect of gangliosides is more potent on quiescent, confluent cells than quiescent, sparse cells. These results demonstrate that exogenously added gangliosides can have opposite (bimodal) effects on progression of human glioma cells through the cell cycle depending upon the growth phase of the cells. © 1995 Wiley‐Liss, Inc.
β‐Amyloid peptide fragment 25–35 potentiates the calcium‐dependent release of excitatory amino acids from depolarized hippocampal slices
Authors: Arias C. , Arrieta I. , Tapia R. 
Published: January 2005

Abstractβ‐Amyloid protein (βAP) has been frequently associated with the neuropathology of Alzheimer's disease (AD), although the mechanisms by which it can induce neurodegeneration are still unknown. Some studies in hippocampal cultured neurons suggest that βAP, particularly its fragment 25ndash;35, may induce neural growth or render neurons more vulnerable to excitotoxic insults by a mechanism involving intracellular Ca2+ dyshomeostasis. We have studied the effect of fragment 25–35 on the release of endogenous amino acids from hippocampal slices of young adult (3–3.5‐month‐old) and aged (23–25‐month‐old) rats, under basal, K+ ‐depolarization, and post‐depolarization conditions, in the presence and absence of Cat2+. In both young and aged tissue, the basal release of amino acids was not affected by the peptide. By contrast, 1‐hr preincubation of slices from young animals with 10 μM 25–35 fragment resulted in a 140% increase of glutamate and aspartate release stimulated by K+ depolarization, compared with the control‐stimulated release. These effects were strictly dependent on external Ca2+ Neither the K+ ‐stimulated release of γ‐amino butyric acid (GABA) nor the release of glycine, glutamine, taurine, or alanine, which was not stimulated by high K+, were affected. Substance P and a scrambled sequence of the 25–35 fragment were without any effect per se, but substance P blocked the stimulatory effect of fragment 25–35 on glutamate and aspartate release. In slices from aged rats the basal release of glutamate was significantly higher (260%) than that in young tissue, and the K+ ‐induced release of both aspartate and glutamate was also higher. Fragment 25–35 also potentiated the K+ ‐induced release of these two amino acids, although to a lesser extent than in young tissue. These results indicate that glutamate is retained less by the aged hippocampus and that fragment 25–35 is able to augment the release of glutamate and aspartate under excitatory conditions, an effect that could be involved in the mechanisms of neurotoxicity of β‐amyloid peptides. © 1995 Wiley‐Liss, Inc.
Protein kinase C‐α and ‐ε are enriched in growth cones of differentiating SH‐SY5Y human neuroblastoma cells
Authors: Parrow V. , Fagerström S. , Meyerson G. , Nånberg E. , Påhlman S. 
Published: January 2005

AbstractSH‐SY5Y cells differentiate into neuronal‐like cells and express marker proteins like growth‐associated protein (GAP‐43) and neuropeptide tyrosine when treated with a low concentration (16 nM) of the phorbol ester 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in the presence of growth factors or serum. Both control and differentiated cells expressed protein kinase C‐α (PKC‐α), PKC‐ε, and PKC‐ζ as revealed by Western blot analyses, but the subcellular distribution of the three isoforms was not uniform, indicating specific localized functions of the enzymes. In growth cones prepared from differentiating cells PKC‐α and PKC‐ε were enriched. In contrast, PKC‐ζ was more evenly distributed within the differentiating cell. Cells treated with a high concentration of TPA (1.6 μM) differentiate poorly and continue to proliferate. In those cells, PKC‐α and PKC‐ε were found to be down‐regulated while PKC‐ζ remained present. Thus, down‐regulation of PKC‐α and PKC‐ζ appears to be incompatible with neuronal differentiation of SH‐SY5Y cells. These cells also differentiate when treated with a combination of basic fibroblast growth factor and insulin‐like growth factor I. Growth cones isolated from such cells are also enriched in PKC‐α and PKC‐ε, but not in PKC‐ζ. Based on the subcellular distribution of PKC‐α and ε, and that PKC substrates like GAP‐43 and pp60c‐src are enriched in SH‐SY5Y growth cones, a role during neurite growth is suggested. © 1995 Wiley‐Liss, Inc.