Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.37 (CNPase)
 539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copper deficiency induced by a low copper diet in three generations of rats was associated with substantial reductions in the yield of myelin (56%), brain weight (11%), and body weight (43%) in F2 generation rat pups nursed by their own copper-deficient mothers. The composition of the purified myelin was not different from that of controls in the content of individual proteins, lipids, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity, or GM1 ganglioside. The major myelin-associated glycoprotein (mGP) was consistently shifted slightly toward higher apparent molecular weight in the copper-deficient animals. Postnatal copper replacement by a foster mother produced a normal yield of myelin per gram of brain tissue, but failed to reverse the deficiency of brain and body growth. After copper replacement in a copper-deficient mother's diet prior to conception, a subsequent litter showed correction of all abnormalities found in her previous litters. The results suggest that copper is essential for myelin formation and general growth during critical periods in development.
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PMID:Hypomyelination in copper-deficient rats. Prenatal and postnatal copper replacement. 125 45

The wet weight, copper content, mitochondrial electron-transfer complexes and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) were measured in various organs including brain, liver, kidney, and heart in macular mutant mice which are considered to be an appropriate model for human Menkes kinky hair disease (MKHD). Copper contents were decreased markedly in liver, brain, and heart. However a significant increase was noted in kidney, suggesting a disproportionate distribution of copper contents in each organ in this mutant mouse. Regarding mitochondrial electron-transfer complexes, only cytochrome c oxidase, a copper dependent enzyme, was found to be decreased in heart and brain. This alteration in the brain was already demonstrated at 2 days. CNPase was not decreased in its activity at 7 days, but decreased at 14 days, supporting progressive demyelination. These results suggested that this mutant mouse would be a useful animal model for clarifying the pathogenesis in human MKHD.
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PMID:[A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease. I. Copper contents and copper dependent enzyme activities in various organs]. 217 32

Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A). In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene) is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes). This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.
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PMID:Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain. 2693 6

Ceruloplasmin (Cp), an enzyme containing six copper atoms, has important roles in iron homeostasis and antioxidant defense. After spinal cord injury (SCI), the cellular components in the local microenvironment are very complex and include functional changes of resident cells and the infiltration of leukocytes. It has been confirmed that Cp is elevated primarily in astrocytes and to a lesser extent in macrophages following SCI in mice. However, its expression in other cell types is still not very clear. In this manuscript, we provide a sensible extension of these findings by examining this system within a female Sprague-Dawley rat model and expanding the scope of inquiry to include additional cell types. Quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that the Cp mRNA and protein in SCI tissue homogenates were quite consistent with prior publications. However, we observed that Cp was expressed not only in GFAP+ astrocytes (consistent with prior reports) but also in CD11b+ microglia, CNPase+ oligodendrocytes, NeuN+ neurons, CD45+ leukocytes, and CD68+ activated microglia/macrophages. Quantitative analysis proved that infiltrated leukocytes, activated microglia/macrophages, and astrocytes should be the major sources of increased Cp.
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PMID:Increased ceruloplasmin expression caused by infiltrated leukocytes, activated microglia, and astrocytes in injured female rat spinal cords. 2937 94