Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ref-1 is a nuclear protein that possesses DNA repair activity and has a role in the redox activation of Fos and Jun transcription factors. Using an antibody to Ref-1 we investigated the expression and distribution of this protein in the adult rat brain. Ref-1 was located in the nucleus of neurons and glial fibrillary acidic protein-positive astrocytes throughout the brain. Levels were particularly high in granule cells of the dentate gyrus, piriform cortex neurons, and Purkinje cells of the cerebellum, and lower in CA1 pyramidal cells, striatal neurons, and the neurons of the neocortex. These results suggest that the action of inducible transcription factors such as c-Jun in mammalian neurons is likely to be regulated by constitutively expressed Ref-1, in particular in dentate granule cells. The high levels of Ref-1 in glial fibrillary acidic protein-positive astrocytes suggest that it may also modulate the action of inducible transcription factors in these cells, particularly after brain injury. The possibility also exists that Ref-1 may primarily function as a DNA repair enzyme in brain cells.
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PMID:Ref-1 expression in adult mammalian neurons and astrocytes. 764 43

Dietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfursion in an animal model. Ung(+/+) and Ung(-/-) mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung(-/-) FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung(+/+) FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung(-/-) hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion or UNG deficiency is required.
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PMID:Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. 2565 13