Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester (CV159) exhibits selective blocking of Ca(2+)/calmodulin and inhibits Ca(2+) overloading in living organisms. The effects of this antagonist in mice with hepatic ischemia-reperfusion injury were investigated using electron paramagnetic resonance imaging (EPRI) and ex vivo EPR (x-band EPR) techniques. The EPRI determined that the 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl half-life in CV159-treated mice was significantly shorter than that in untreated mice and was almost equal to that in the sham group. Both the cytosolic and the mitochondrial superoxide scavenging activities in CV-treated mice were significantly higher than that in untreated mice. Faint staining of the anti-superoxide dismutase antibody and strong staining of anti-inducible nitric oxide synthase antibody were observed in the liver of control group. In contrast to these findings, immunostaining of these antibodies in the liver of CV159-treated mice were reversed compared to control group. Western blotting showed that CV159 contributed to the high superoxide dismutase expression and low expression of inducible nitric oxide synthase. The alanine aminotransferase level in CV159-treated mice significantly decreased in comparison to that observed in the untreated mice. We conclude that CV159 retains its organ-reducing activity against radicals in hepatic reperfusion injury, which is mediated by the inhibition of Ca(2+) overloading.
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PMID:Effect of CV159-Ca(2+)/calmodulin blockade on redox status hepatic ischemia-reperfusion injury in mice evaluated by a newly developed in vivo EPR imaging technique. 1806 26

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome.
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PMID:Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions. 2073 62