Abstract:
:There is ample evidence that both acid (ASMase) and neutral (NSMase) sphingomyelinases play a role in cell death so inhibitors of either enzyme could have significant value as protectors against neurodegeneration. We used a fluorogenic sphingomyelinase substrate, 6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine, and a [(14)C]choline-labeled sphingomyelin substrate to screen large numbers of phosphocompounds for inhibition of ASMase in extracts of human oligodendroglioma cells (HOG) and neonatal rat oligodendrocytes. Non-competitive inhibition was observed with inorganic phosphate and AMP, which was a more potent inhibitor of ASMase than cyclic AMP, ADP or ATP. However, other nucleotide phosphates, sugar phosphates, nucleotide sugars and glycerol phosphate did not inhibit ASMase. Our key finding was that phosphatidyl-myo-inositol 3,4,5-triphosphate [PtdIns (3,4,5)P(3)] was a much more potent inhibitor of ASMase than lysophosphatidic acid or phosphatidyl-myo-inositol 4,5-diphosphate [PtdIns(4,5)P(2)]. When PtdIns(3,4,5)P(3) was added to cultured cells we observed 50% inhibition of ASMase but no inhibition of other lysosomal hydrolases. After transfection of HOG cells with the tumor supressor phosphatase and tensin homolog protein (PTEN), which hydrolyses PtdIns(3,4,5)P(3) to PtdIns(4,5)P(2), we observed a two-fold increase in ASMase activity. Furthermore, the phosphatidylinositol-3-kinase inhibitor wortmannin (which reduces PtdIns(3,4,5)P(3) levels) also resulted in activation of ASMase. We propose that the small amount of ASMase activity associated with detergent-resistant cell membranes (Rafts) is regulated by PtdIns(3,4,5)P(3) and is most likely involved in receptor clustering and capping.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Testai FD,Landek MA,Goswami R,Ahmed M,Dawson Gdoi
10.1046/j.1471-4159.2004.02374.xkeywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
636-44issue
3eissn
0022-3042issn
1471-4159pii
JNC2374journal_volume
89pub_type
杂志文章abstract::The ontogenesis of rat forebrain adenosine uptake sites labelled by [3H]nitrobenzylthioinosine ([3H]NBI) was determined and compared to that of rat forebrain adenosine receptors labelled by N6-cyclohexyl[3H]adenosine ([3H]-CHA). [3H]NBI binding is highly invariant with similar levels of [3H]NBI binding sites from embr...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb00972.x
更新日期:1987-09-01 00:00:00
abstract::In contrast to brain, the sciatic nerve concentration of vitamin E in rats increased rapidly during the postnatal period (approximately fivefold between days 1 and 8), then decreased dramatically (about twofold between days 8 and 30), and further decreased slowly between days 30 and 60 and remained constant up to 2 ye...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb04917.x
更新日期:1990-06-01 00:00:00
abstract::Platelet-activating factor (PAF) is a potent lipid mediator implicated in various pathological conditions, including CNS neuronal injury. However, the production of PAF by mammalian CNS neurons has not as yet been demonstrated. In the present study, we demonstrate that PAF is produced by cultured rat cerebellar granul...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb01239.x
更新日期:1990-05-01 00:00:00
abstract::The accumulation of choline, homocholine, and 4-hydroxybutyltrimethylammonium by rat brain synaptosomes was measured; the choline uptake mechanism transported homocholine but not hydroxybutyltrimethylammonium, which, in addition, did not block choline accumulation. In cats' superior cervical ganglia, preganglionic ner...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb01732.x
更新日期:1981-03-01 00:00:00
abstract::The degradation pattern and rate of [Ile5]-Angiotensin (Ang) I, II, and III were studied in neuron-enriched and glia-enriched cells in primary cultures from rat brain. Metabolites were separated by HPLC, and their identities were evaluated by comparison of their retention times with those of synthetic Ang peptide frag...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb02534.x
更新日期:1989-03-01 00:00:00
abstract::In this study, we describe a novel form of anti-homeostatic plasticity produced after culturing spinal neurons with strychnine, but not bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Strychnine caused a large increase in network excitability, detected as spontaneous synaptic currents and calcium transient...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04306.x
更新日期:2007-03-01 00:00:00
abstract::Parameters affecting the binding of [3H]glycine to membrane fractions isolated from the cerebral cortex, midbrain, cerebellum, medulla oblongata, and spinal cord of the rat were investigated in a Na+-free medium. A [3H]glycine binding assay was established in which the binding was specific, saturable, pH-sensitive, an...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb04489.x
更新日期:1981-10-01 00:00:00
abstract::The effects of a potent adenosine deaminase inhibitor, deoxycoformycin, on purine and amino acid neuro-transmitter release from the ischemic rat cerebral cortex were studied with the cortical cup technique. Cerebral ischemia (20 min) was elicited by four-vessel occlusion. Purine and amino acid releases were compared f...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb08198.x
更新日期:1991-02-01 00:00:00
abstract::We have identified a novel mouse gene named pancortin that is expressed dominantly in the mature cerebral cortex. This gene produces four different species of proteins, Pancortin-1-4, sharing a common region in the middle of their structure with two variations at the N-terminal (A1 or A2 part) and C-terminal (C1 or C2...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0750001.x
更新日期:2000-07-01 00:00:00
abstract::We have examined cyclic GMP concentrations, guanylate cyclase activities, and cyclic GMP phosphodiesterase (PDE) activities in developing retinas of congenic mice with different allelic combinations at the retinal degeneration (rd) and retinal degeneration slow (rds) loci. Although guanylate cyclase activities were fo...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00644.x
更新日期:1986-04-01 00:00:00
abstract::To examine the effects of glutamatergic neurotransmission on amyloid processing, we stably expressed the metabotropic glutamate receptor subtype 1alpha (mGlu-R1alpha) in HEK 293 cells. Both glutamate and the selective metabotropic agonist 1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) rapidly increased phosphatidyli...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69020704.x
更新日期:1997-08-01 00:00:00
abstract::1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to cause a destruction of the dopaminergic nigrostriatal pathway in certain animal species including mice. MPTP and some structurally related analogs were tested in vitro for their capacity to inhibit the uptake of [3H]3,4-dihydroxyphenylethylamine-([3H]DA),...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb07146.x
更新日期:1985-01-01 00:00:00
abstract::Increasing evidence suggests that glucagon-like peptide-1 (GLP-1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP-1 and associated underlying mechanisms, we over-expressed the GLP-1 receptor (G...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06731.x
更新日期:2010-06-01 00:00:00
abstract::Uptake of L-glutamine (2 mM) by rat brain cortex slices against a concentration gradient is markedly inhibited (40%) by branched-chain L-amino acids (1 mM), L-phenylalanine (1 mM), or L-methionine (1 mM); that of L-asparagine (2 mM) is much less affected by these amino acids. Other amino acids investigated have little...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb12491.x
更新日期:1980-07-01 00:00:00
abstract::The present study demonstrates that [3H]imipramine binds to both high- and low-affinity imipramine binding components on membranes prepared from rat cerebral cortex. Scatchard and computer analyses of saturation experiments using a wide range of [3H]imipramine concentrations (0.5 nM-50 nM) revealed the presence of two...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb05494.x
更新日期:1985-07-01 00:00:00
abstract::Schwann cells provide a favorable microenvironment for successful regeneration of the injured peripheral nerve. Even though the roles of extracellular matrix proteins in the Schwann cell physiology have long been studied, the precise function of nidogen, a ubiquitous component of the basal lamina, in Schwann cells is ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04580.x
更新日期:2007-08-01 00:00:00
abstract::Three forms of acetylcholinesterase (AChE) have been reported: the 4S, 10S, and 16S forms. It was suggested previously that 16S AChE is characteristic of the end-plate region; subsequently its presence has also been demonstrated in sciatic nerve, vagus nerve, several nerve trunks, cardiac atria, and distal ileum of ra...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb10882.x
更新日期:1982-01-01 00:00:00
abstract::Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13946
更新日期:2017-03-01 00:00:00
abstract::We have studied the responsiveness of vascular adenylate cyclase to vasoactive intestinal peptide (VIP) and parathyroid hormone (PTH) using preparations of cerebral microvessels and arteries. Cerebral microvessels obtained from rats, guinea-pigs, cattle, and pigs all responded potently to bovine (b) PTH-(1-34), wherea...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb12808.x
更新日期:1984-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.63020758.x
更新日期:1994-08-01 00:00:00
abstract::Somatodendritic voltage-dependent K(+) currents (Kv4.2) channels mediate transient A-type K(+) currents and play critical roles in controlling neuronal excitability. Accumulating evidence has indicated that Kv4.2 channels are key regulatory components of the signaling pathways that lead to synaptic plasticity. In cont...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05356.x
更新日期:2008-07-01 00:00:00
abstract::The effect of glucocorticoids on polyamine metabolism has been elucidated further by measuring putrescine, spermidine, and spermine levels as well as ornithine decarboxylase, S-adenosylmethionine decarboxylase, and N1-acetylspermidine transferase activities in the hippocampus, cerebellar cortex, vermis, and deep nucle...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb01797.x
更新日期:1988-09-01 00:00:00
abstract::Math2 (NEX-1/NeuroD6) is a member of the basic helix-loop-helix transcription factor family and is involved in neuronal differentiation and maturation. In this study, we identified the genes targeted by Math2 using DNA microarrays and cultured rat cortical cells transfected with Math2. Of the genes regulated by Math2,...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05579.x
更新日期:2008-09-01 00:00:00
abstract::Therapy of malignant glioma relies on treatment with the O6 -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences, DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O6 -alkylguanine. Since this dama...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14262
更新日期:2018-01-01 00:00:00
abstract::Dopamine neurons have been suggested to use glutamate as a cotransmitter. To identify the basis of such a phenotype, we have examined the expression of the three recently identified vesicular glutamate transporters (VGLUT1-3) in postnatal rat dopamine neurons in culture. We found that the majority of isolated dopamine...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.02277.x
更新日期:2004-03-01 00:00:00
abstract::Based on our initial finding that the nitric oxide (NO) sensitive fluorochrome diaminofluorescein (DAF) was localized to mitochondria in cultured primary neurons, we investigated whether brain mitochondria produce NO through a mitochondrial NO synthase (mtNOS) enzyme. Isolated brain mitochondria were loaded with DAF a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02553.x
更新日期:2004-08-01 00:00:00
abstract::The proteasome is a multiprotein complex that is involved in the intracellular protein degradation in eukaryotes. Here, we show that human malignant glioma cells are susceptible to apoptotic cell death induced by the proteasome inhibitors, MG132 and lactacystin. The execution of the apoptotic death program involves th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0752288.x
更新日期:2000-12-01 00:00:00
abstract::Previous work from this laboratory has shown that in PC12 cells the phosphorylation of a specific soluble protein is decreased by nerve growth factor treatment. The protein, designated Nsp100, and its kinase have been separated and partially purified from PC12 cells. In the present work, the tissue distribution of Nsp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb05554.x
更新日期:1985-10-01 00:00:00
abstract::Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12613
更新日期:2014-04-01 00:00:00
abstract::PC12D cells, a new subline of conventional PC12 cells, respond not only to nerve growth factor but also to cyclic AMP by extending their neurites. These cells are flat in shape and are similar in appearance to PC12 cells that have been treated with nerve growth factor for a few days. In both cell lines, we have charac...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb02538.x
更新日期:1989-03-01 00:00:00