Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional significance of peroxynitrite in the release of [3H]GABA induced by nitric oxide (NO) liberated from NO generators was investigated using cerebral cortical neurons in primary culture. NO generators such as sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) increased [3H] GABA release in a dose-dependent manner. These increases in [3H]-GABA release were significantly inhibited by hemoglobin, indicating that those NO generators evoke the release of [3H] GABA by the formation of NO. Two types of superoxide scavengers, Cu2+/Zn2+ superoxide dismutase and ceruloplasmin, significantly reduced the increase in [3H]-GABA release induced by both SNP and SNAP, which assumes that NO requires superoxide to induce [3H]-GABA release from the neurons. In addition, synthesized peroxynitrite induced a dose-dependent increase in [3H]-GABA release from the neurons. These results indicate that NO-induced [3H] GABA release is mediated by peroxynitrite formed by the reaction of NO with superoxide.
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PMID:Nitric oxide-induced [3H] GABA release from cerebral cortical neurons is mediated by peroxynitrite. 764 88

For the development of new drugs for hitherto untreatable epilepsy, it is necessary to clarify the basic pathophysiology involved in such epileptic seizures and find the target site. This review focused on molecular events related to the expression and expansion of the epileptic focus which are the target of novel antiepileptics. Immediate early genes such as c-fos followed by expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been evidenced as initial important phenomena in the cascade of molecular systems that develop and complement the transient neuronal excitation to long-term neuronal plasticity. Non-receptor type tyrosine kinase Fyn in the Src family has been suggested to promote kindling development via tyrosine phosphorylation of the NMDA-receptor subunit, NR2B. The cause of abnormality in the inhibitory system is induced by lowering of glutamate-dependent GABA release in the epileptic focus within the hippocampus in human temporal epilepsy. This is probably attributed to a decrease in GABA transporters. Regarding abnormality of the excitatory system, there is an increase in glutamate release prior to convulsive seizures, an enhancement of NMDA receptor responsiveness and high levels of AMPA receptors related to convulsion after completion of kindling. In gene analysis of human familiar epilepsy, abnormalities and point mutations have recently been found in the following genes: KCNQ 2 and KCNQ3, coding for K+ channels; CHRNA4 of the nicotinic receptor subunit alpha 4; and the cystatin B gene. In epilepsy model mice, EL mice with several gene mutations known to be involved in the seizures, the El-1 gene contains an abnormality of the ceruloplasmin gene. SER (spontaneously epileptic rat: zi/zi, tm/tm), a double mutant, manifests a deletion of the region containing the aspartoacylase gene related to the tm gene. Since an increase in N-acetyl-L-aspartate (NAA) is observed in the SER brain, NAA may serve to evoke seizures.
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PMID:[Molecular mechanism underlying epileptic seizure: forwards development of novel drugs for untreatable epilepsy]. 1055 79

Various stages of hypokinesia are marked by specific changes in the level and activity of endogenous metalloproteins with anti- (MAA) and prooxidant action (MPA). In particular, the level of MPA [cytochromes b5 and b558 (III + IV) and suprol] decreases in all stages (except for the level of cytochrome b5 exceeding that in the free control on the 15th and 30th day of hypokinesia). The superoxide production activity of suprol always exceeds that in the control, while the activity of cytochrome b558 (III) exceeds that in the control only on the 30th day of experiment. The level and activity of MAA [ceruloplasmin, transferrin (TF), superoxide dismutase (SOD), and catalase] decrease with the duration of hypokinesia (except for 15th day, when the level of TF and the activity of SOD exceed the values in the free control group). The administration of GABA and pyrrolidone decreases the extent of oxidative stress, which is manifested by leveling of the MAA and MPA content and activity.
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PMID:[Regulating effect of gamma-aminobutyric acid and pyrrolidone-2 on endogenous blood metalloproteins with anti- and pro-oxidant activity in hypoxia]. 1507 5

It has previously been reported that men with developmental stuttering showed reduced concentration of copper in the blood, and a negative correlation between the copper level and the severity of stuttering. Disorders of copper metabolism may result in dysfunction of the basal ganglia system and dystonia, a motor disorder sharing some traits of stuttering. It has been shown that copper ions affect the dopamine and the GABA systems. With this background we investigated the plasma level of copper, the copper binding protein ceruloplasmin, and the estimated level of free copper in stuttering adults. Sixteen men with developmental stuttering were compared with 16 men without speech problems. The samples were assayed in one batch in a pseudorandom and counterbalanced order. No significant differences were found between stuttering men and the control group in any of the biological variables, and no negative correlation between copper and the general severity of stuttering was shown. On the contrary, an explorative analysis resulted in a positive correlation between high plasma copper and superfluous muscular activity during stuttering (r=0.51, p=0.04). This result indicates that there is no relation between developmental stuttering and low plasma copper in the main population of stuttering adults.
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PMID:Copper in developmental stuttering. 1603 97

Neurons in the hippocampal CA1 region are particularly sensitive to oxidative stress (OS), whereas those in CA3 are resistant. To uncover mechanisms for selective CA1 vulnerability to OS, we treated organotypic hippocampal slices with duroquinone and compared transcriptional profiles of CA1 vs CA3 cells at various intervals. Gene Ontology and Biological Pathway analyses of differentially expressed genes showed that at all time points, CA1 had higher transcriptional activity for stress/inflammatory response, transition metal transport, ferroxidase, and presynaptic signaling activity, while CA3 had higher GABA-signaling, postsynaptic, and calcium and potassium channel activity. Real-time PCR and immunoblots confirmed the transcriptome data and the induction of OS by duroquinone in both hippocampal regions. Our functional genomics approach has identified in CA1 cells molecular pathways as well as unique genes, such as guanosine deaminase, lipocalin 2, synaptotagmin 4, and latrophilin 2, whose time-dependent induction following the initiation of OS may represent attempts at neurite outgrowth, synaptic recovery, and resistance against OS.
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PMID:Genome-wide transcriptome profiling of region-specific vulnerability to oxidative stress in the hippocampus. 1755 63

Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.
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PMID:Copper and copper proteins in Parkinson's disease. 2467 33