bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin‐like growth factor I stimulates oligodendrocyte development and myelination in rat brain aggregate cultures
Authors: Mozell R. L. , McMorris F. A. 
Published: January 2005

AbstractInsulin‐like growth factor I (IGF‐I) and high concentrations of insulin have been shown to stimulate an increase in the number of oligodendrocytes that appear in developing monolayer cultures of rat brain cells (McMorris et al., Proc Natl Acad Sci USA 83:822–826, 1986; McMorris et al., Ann NY Acad Sci 605:101–109, 1990; McMorris and Dubois‐Dalcq, J Neurosci Res 21:199–209, 1988). In the present study, we investigated whether IGF‐I or insulin treatment induces a corresponding increase in the synthesis and accumulation of myelin. Aggregate cultures, established from 16‐day‐old fetal rat brains, were treated with either 100 ng/ml IGF‐I or 5,000 ng/ml insulin and analyzed for the number of oligodendrocytes, activity of 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNP), total amount of myelin, and synthesis rate of myelin proteins. Cultures treated with IGF‐I beginning on day 2 after explanation contained 35–80% more oligodendrocytes and had 60–160% higher CNP activity than controls when tested on day 13, 20, or 27. By day 27, treated cultures had 35–90% more myelin than controls. Similar results were observed in response to 5,000 ng/ml insulin, a concentration at which insulin binds to IGF receptors and acts as an analogue of IGF‐I. The synthesis rate of myelin proteins was measured in experiments using 5,000 mg/ml insulin. When treatment was begun at day 20 rather than day 2, cultures did not exhibit an increased number of oligodendrocytes over control during the following 4–6 days. Therefore, this paradigm was used to separate the effects of insulin‐like peptides on the number of oligodendrocytes from the effects on the synthesis rate of myelin proteins and the accumulation of myelin. Cultures treated from day 20 and controls showed no difference in either the myelin yield or the synthesis rate of myelin proteins. These data show that IGF‐I (and insulin at high concentrations) increases the amount of myelin produced in aggregate cultures; and that the increase appears to be due primarily to an increase in the number of oligodendrocytes in the cultures rather than to a direct increase in the rate of myelin protein synthesis or an increase in the amount of myelin synthesized per oligodendrocyte.
Brain cysteine proteinase inhibitors II: Evidence that a 21‐kDa papain‐binding component resembles ras p21
Authors: Berg M. J. , Marks N. 
Published: January 2005

AbstractA 21‐kDa protein extracted from rat or bovine brain at high pH was purified on alkylated‐papain and shown to have dual ras like and cysteine proteinase inhibitory (CPI) properties. This was demonstrated by its GTP‐binding activity, cross‐reactivity toward pan‐reactive ras p21 monoclonal antibody, and inhibition of papain. The material eluted earlier than cystatins or kininogens on the alkylated papain‐affinity column and was devoid of other CPIs based on immunoblot analysis. In a second procedure, ras p21s isolated from rat or bovine brain membranes by cholate extraction and purified by gel‐permeation and hydrophobic interaction were shown to act also as potent CPIs, inhibiting rat brain cathepsin L, pa‐pain, or rat brain cathepsin B with K1 values of 3, 11, and 167 nM, respectively. This component cross‐reacted with the monospecific anti‐ras, but not with other anti‐CPIs, and represented 3–4% of total GTP binding present in homogenates. The specific activity of the purified 21 kDa component was 4.7 nmol GTP‐γ‐S bound per mg protein. The data support the notion that brain ras p21s constitute a separate group of CPIs and are available for regulating some aspects of brain protein turnover.
Rat retina has an active and stable ubiquitin–protein conjugating system
Authors: Naash M. , Izbicka E. , Anderson R. E. 
Published: January 2005

AbstractWe describe here the presence of ubiquitin and its conjugation system in the rat retina. Retinal homogenates and supernatants conjugate [125I] human ubiquitin with either endogenous or exogenous proteins. The conjugating activity is relatively stable over time, requires ATP, and has a pH optimum of ∼8. The most prominent [125I]ubiquitin conjugates formed are larger than 130 kDa. Several other minor conjugates are also formed between the molecular weights 17 and 75 kDa. The endogenous levels of free and conjugated forms of ubiquitin have been determined in the rat retina. More than 50% of retinal ubiquitin is covalently bound to target proteins. In addition, activities responsible for the ATP‐dependent degradation and disassembly of both endogenous and exogenous ubiquitin conjugates have been detected in vitro. These results provide evidence that the retina contains active and stable ubiquitin‐conjugating enzymes that recognize retinal proteins and have ATP‐dependent proteolytic activity.
Phosphorylation of MARCKS (80‐KDA) protein, a major substrate for protein kinase C in oligodendroglial progenitors
Authors: Bhat N. R. 
Published: January 2005

AbstractWe have recently reported a potent mitogenic stimulation of oligodendroglial (OL) progenitors by the protein kinase C (PKC) activating phorobol ester, i.e., phorbol 12‐myristate 13‐acetate (PMA) (Bhat NR, J Neurosci Res 22:20–27, 1989). The present study deals with PMA‐induced protein phosphorylation reactions in cultured OL progenitors. The phorbol ester induced the phosphorylation of several cytosol and membrane‐associated proteins, including a major protein with an apparent molecular weight of 80 kDa. In both control and PMA‐treated cultures, phosphorylation level of the 80‐kDa protein in cytosol was higher than that in the particulate fraction. Okadaic acid, an inhibitor of protein phosphatases, also increased the phosphorylation of several proteins and substantially enhanced protein phosphorylation induced by PMA. In vitro incubation of the cell membranes with phosphatidylserine and diacylglycerol (a physiological activator, of PKC) in the presence of [γ32p]‐ATP resulted in an increased phosphorylation of the 80‐kDa protein. The induction of phosphorylation of the 80‐kDa protein under both in situ and in vitro conditions was subject to inhibition by l‐[5]isoquinolinyl sulfonyl)‐3‐methylpiperazine (H‐7), a potent inhibitor of PKC. The 80‐kDa phosphoprotein was identified as the prominent PKC substrate, i.e., myristoylated alanine‐rich C‐kinase substrate (MARCKS) protein by immunoprecipitation with anti‐MARCKS antibodies.
Temporal changes in edema, Na+, K+, and Ca++ in focal cortical stroke: GM1 ganglioside reduces ischemic injury
Authors: Karpiak S. E. , Wakade C. G. , Tagliavia A. , Mahadik S. P. 
Published: January 2005

AbstractCortical focal ischemia in the rat was induced by middle cerebral artery occlusion (MCAo) together with permanent occlusion of the ipsilateral common carotid artery (CCAo) and a temporary (1 hr) occlusion of the contralateral CCA. By using a defined cortical tissue sampling procedure at 3, 6, 24, 72, 96, and 120 hr after the MCAo + CCAo, patterns of edema and ion (Na+, K+, and Ca++) changes in a primary and three peri‐ischemic cortical areas are described. Ionic imbalances and edema formation have distinct patterns, are time dependent, and are different when comparing primary and peri‐ischemic areas. Calcium increases to “neurotoxic” levels appear temporally independent of edema formation, reaching magnitudes 20 times greater than basal levels in the pri‐mary infarct area. Na+ increases correlate with increases in water, while K+ losses do not appear to be directly related to edema formation or Na+ and Ca++ increases. K+ losses are only significant in the primary infarct area. Rats treated with GM1 ganglioside (10 mg/kg, i.m.) daily showed significant reductions in edema, Na + and Ca ++ increases. These ganglioside effects were evident as early as 24 hr after the ischemic injury. Ca++ increases, which was maximal at 72 hr after the ischemic injury, was reduced by greater than 50% in GM1‐treated animals. The mechanism by which GM1 is an effective neuroprotective agent may be evidenced by its effects on Ca++ influx/efflux processes in injury.
GABA‐ and glutamate‐activated currents in glial cells of the mouse corpus callosum slice
Authors: Berger T. , Walz W. , Schnitzer J. , Kettenmann H. 
Published: January 2005

AbstractWhole‐cell transmitter‐activated currents were recorded with the patch‐clamp technique from glial cells in thin frontal brain slices of the corpus callosum. In slices from 6‐ to 8‐day‐old mice, glioblasts were predominantly found, while oligodendrocytes were predominant in slices from 10‐ to 13‐day‐old mice. These developmental stages could be readily distinguished by their K+ channel pattern and their morphology and ultrastructural features. Both cell types expressed GABA and glutamate receptors in this in situ preparation. GABA responses showed similarities to those described for GABAA receptors, i.e., they were mimicked by muscimol, blocked by bicuculline, and enhanced by pentobarbital. Glutamate responses showed similarities to those of the kainate/quisqualate receptor subtype. The amplitude of GABA‐activated currents recorded in oligodendrocytes was significantly smaller than that from glioblasts, while glutamate responses did not show marked differences in either cell type.
Effect of dexamethasone on the nerve growth factor‐induced increase in the NILE glycoprotein in PC12 cells
Authors: Tocco M. D. , Fujita K. , Guroff G. 
Published: January 2005

AbstractThe long‐known and well‐documented increase in the NILE glycoprotein produced by nerve growth factor in PC12 cells is prevented by simultaneous treatment with dexamethasone. The absence of this surface marker on the fully differentiated cells has been demonstrated by both glucosamine incorporation and immunohistofluorescence.
Dexamethasone blocks nerve growth factor induction of nerve growth factor receptor mRNA in PC12 cells
Authors: Foreman P. J. , Taglialatela G. , Jackson G. R. , Perez‐Polo J. R. 
Published: January 2005

AbstractGlucocorticoids and nerve growth factor (NGF) have been shown to have antagonistic effects on chromaffin cells in vivo. Here we determined the effect of the synthetic glucocorticoid, dexamethasone, on levels of mRNA for the nerve growth factor receptor (NGFR) in rat PC12 pheochromocytoma cells. Following administration of dexamethasone (1 μM) there is a decline in NGFR mRNA expression. More importantly, administration of dexamethasone appears to block the NGF‐mediated induction of NGFR when both agents are administered simultaneously. These data support the hypothesis that glucocorticoids and NGF act in opposition in determination of the phenotype of chromaffin cells.
Expression of plasmolipin in the developing rat brain
Authors: Sapirstein V. S. , Nolan C. E. , Stadler I. I. , Fischer I. 
Published: January 2005

AbstractPlasmolipin is an hydrophobic plasma membrane proteolipid present in both kidney and brain. The protein consists of two subunits of 17–18.5 kD, which together form K+ selective voltage‐dependent channels. In this report, we define the embryonic and postnatal expression of plasmolipin in the developing rat brain. Plasmolipin was found to be essentially restricted to the postnatal period increasing eight‐fold between the first to fourth week after birth. A fetal plasmolipin immunoreactive protein (FPIP) was identified in embryonic brain and also during the early postnatal development of the cerebellum. The expression of FPIP was biphasic with an initial transient increase between E15‐E20 followed by a decrease in its levels. FPIP was not detected in the developed rat CNS. FPIP was found in a variety of dividing and immature cells including cultured astrdcytes and embryonic neurons, neuroblastoma cells, and rat thymus. In contrast, plasmolipin was restricted to oligodendrocytes of the neural cells tested and to renal tubular epithelial cells.
MPTP‐induced parkinsonism: Acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment
Authors: Schneider J. S. 
Published: January 2005

AbstractThe effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin l‐methyl‐4‐phenyl‐ 1,2,3, 6‐tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1‐treated cats had caudate nucleus dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline‐treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1 ‐treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP‐induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease.
Interaction of multiple nuclear proteins with the promoter region of the mouse 68‐kDa neurofilament gene
Authors: Ivanov T. R. , Brown Ian R. 
Published: January 2005

AbstractFour brain‐specific, DNase I hypersensitive sites (HSS) have been mapped to the 5′ flanking region of the mouse 68‐kDa neurofilament gene. These sites are contained within a 1.7‐kb sequence that confers neuronal specificity of expression on this gene in transgenic mice. To identify DNA sequences that might be involved in gene regulation, the HSS situated near the promoter region has been analyzed by gel mobility shift assays and DNase I footprinting to investigate protein binding sequences. Of particular interest are two footprints localized to a 9‐nucleotide sequence that flanks both the light and medium neurofilament gene in mouse and to a sequence that demonstrates partial homology to several promoter regions, including element‐1, a motif required for neuron specificity in Drosophila. A prominent footprint was also detected at a sequence that contains a near‐perfect palindrome centered at a PstI restriction site. © 1992 Wiley‐Liss, Inc.
Molecular cloning of a novel mRNA using an antibody directed against synaptic glycoproteins
Authors: Johnston I. G. , Rush S. J. , Gurd J. W. , Brown Ian R. 
Published: January 2005

AbstractIt has been suggested by a number of investigators that glycoproteins may play a role in the development and/or maintenance of synapses in the mammalian CNS. For many synaptic glycoproteins, however, little precise structural or functional information is available. In an effort to isolate probes specific to individual glycoproteins, we have screened a rat brain cDNA expression library with a mixed polyclonal antibody directed against concanavalin A‐binding synaptic junctional glycoproteins. Using this approach, we have previously reported the cloning of SC1, a putative extracellular matrix glycoprotein found in adult brain (Johnston et al., Neuron 2:165–176, 1990). We now report the cloning and characterization of a second novel cDNA, which has been designated SC2. Northern blots show that this cDNA recognizes a 1.2‐kb mRNA that is present throughout postnatal development in the rat. It is expressed at high levels in brain and is also found at lower levels in several other tissues. In situ hybridization suggests that the SC2 mRNA is strongly expressed by many types of neurons. Sequence data reveals a single open reading frame in the cDNA, encoding a putative hydrophobic protein with a calculated molecular weight of 36.1 kDa. Sequence analysis reveals some similarity between SC2 and 5α‐reductase, a microsomal membrane protein important in testosterone metabolism. © 1992 Wiley‐Liss, Inc.
Expression of p75NGFR trkA, and trkB mRNA in rat C6 glioma and type I astrocyte cultures
Authors: Hutton L. A. , DeVellis J. , Perez‐Polo J. R. 
Published: January 2005

AbstractUsing a quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) we have investigated the expression of the neurotrophin receptors p75NGFR, trkA, and trkB, mRNAs in cultures of rat pup type I astrocytes and in the C6 rat glioma cell line. All three neurotrophin receptor mRNAs are expressed in both C6 cells and in type I astrocytic cultures. p75NGFR mRNA levels are increased by either cycloheximide or nerve growth factor (NGF) treatment of C6 cells as measured using RT‐PCR. Type I astrocyte cultures also expressed p75NGFR mRNA and NGF treatment increased p75NGFR mRNA levels in these cultures. TrkB mRNA levels were increased by cycloheximide treatment of type I astrocyte cultures but not by NGF treatment. Using RT‐PCR, trkA mRNA was detected in astrocytic cultures as well as in the rat C6 and PC‐12 cell lines. We conclude that cultures of type I astrocytes express active NGF receptors and that glia can elicit a response to NGF as seen by an increase in p75NGFR mRNA levels following exposure to NGF. © 1992 Wiley‐Liss, Inc.
Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain
Authors: Chandrasekaran K. , Stoll J. , Giordano T. , Atack J. R. , Matocha M. F. , Brady D. R. , Rapoport S. I. 
Published: January 2005

AbstractA frontal pole cDNA library from monkey (Macaca mulatta) brain was screened to identify mRNAs that are expressed more in frontal pole as compared to primary visual cortex. Three cDNA clones, whose greater expression was confirmed by Northern blot analysis, were identified as cytochrome oxidase (COX) subunits I, II, and III (COX I, II, and III). Each clone showed higher levels of mRNA in the frontal pole, dorsal lateral prefrontal cortex, and hippocampus than in the primary visual or somatosensory cortices. COX histochemistry of prefrontal, visual, and somatosensory cortical regions demonstrated heterogeneous distributions, with highest activity in dendrite‐rich neuropil of the cortex. A laminar distribution of COX mRNA expression also was demonstrated with in situ hybridization. mRNA was detected in cell bodies and in apical dendrites. These results indicate region specific differences in the distribution of COX activity and in the corresponding mRNA for three of its subunits within the monkey brain. Such differences may be related to differences in the distribution of neuropil as compared with cell bodies among the brain regions studied, and may be relevant to selective vulnerability in Alzheimer's disease. Published 1992 by Wiley‐Liss, Inc. © 1992 Wiley‐Liss, Inc.
Multiple intracellular signaling pathways of the neuropeptide substance P receptor
Authors: Mitsuhashi Masato , Ohashi Y. , Shichijo S. , Christian C. , Sudduth‐Klinger J. , Harrowe G. , Payan D. G. 
Published: January 2005

AbstractThe rat substance P (SP) receptor cDNA has been transfected into cultured rat KNRK cells, and a stable cell line expressing functional SP receptors established. Upon stimulation with SP, these cells responded by simultaneously activating two signaling pathways: the mobilization of intracellular Ca2+ and the raising of cyclic adenosine triphosphate (cAMP) levels. Both Ca2+ and cAMP responses were elicited in a similar dose‐dependent manner with half maximal concentrations of approximately 5 × 10−10 M. Following ionomycin treatment SP‐dependent Ca2+ responses were abolished, whereas cAMP responses were preserved. Forskolin eliminated the SP‐dependent cAMP elevation, however, the SP‐induced Ca2+ mobilization remained unchanged. Furthermore, treatment with phorbol esters had no significant effect on either of the two SP‐induced responses. Thus it appears that the SP receptor is capable of independently activating Ca2+ mobilization and cAMP pathways. These results may provide new insights for further understanding the diverse activities of SP in various systems in vitro and in vivo. © 1992 Wiley‐Liss, Inc.
Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily
Authors: Gardinier M. V. , Amiguet P. , Linington C. , Matthieu J.‐M. 
Published: January 2005

AbstractMyelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparision with MOG N‐terminal peptide sequence. As expected, MOG mRNA expression is CNS‐specific and peaks during active myelination. Our studies show that full length MOG mRNA is ≈︁ 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N‐glycosylation is found at Asn‐31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N‐terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B‐G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane‐spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members. © 1992 Wiley‐Liss, Inc.
Evidence for intracellular cleavage of the Alzheimer's amyloid precursor in PC12 cells
Authors: Sambamurti K. , Shioi J. , Anderson J. P. , Pappolla M. A. , Robakis N. K. 
Published: January 2005

AbstractThe Alzheimer's amyloid precursor (APP) is cleaved by an unidentified enzyme (APP secretase) to produce soluble APP. Fractionation of PC12 cell homogenates in a detergent‐free buffer showed the presence of the Kunitz protease inhibitor (KPI)‐containing soluble APP (nexin II) in the particulate fraction. Digitonin or sodium carbonate treatment of this fraction solubilized nexin II suggesting that it is contained in the lumen of vesicles. Nexin II production was not affected by lysosomotropic agents, suggesting that APP secretase is not a lysosomal enzyme. Labelling of cell surface proteins by iodination failed to detect full‐length APP on the surface of PC12 cells, suggesting that most of this protein is located intracellularly. Furthermore, pulse‐chase experiments showed that nexin II is detected in cell extracts before it appears in the culture medium. Cellular nexin II was detected at zero time of chase after only 5 min of pulse labelling with 35S‐sulfate, indicated that APP secretase cleavage takes place immediately after APP is sulfated. Temperature block, pulse‐chase, and 35S‐sulfate‐labelling experiments suggested that APP is cleaved by APP secretase intracellularly in the trans‐Golgi network (TGN) or in a post‐Golgi compartment. © Wiley‐Liss, Inc.