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• W2168792406 endingPage "4738" @default.
• W2168792406 startingPage "4727" @default.
• W2168792406 abstract "Reperfusion of ischemic tissue causes an immediate increase in DNA damage, including base lesions and strand breaks. Damage is reversible in surviving regions indicating that repair mechanisms are operable. DNA strand breaks are repaired by nonhomologous end joining in mammalian cells. This process requires DNA-dependent protein kinase (DNA-PK), composed of heterodimeric Ku antigen and a 460,000 Da catalytic subunit (DNA-PKcs). In this study, a rabbit spinal cord model of reversible ischemia was used to demonstrate the effect of acute CNS injury on the activity and expression of DNA-dependent protein kinase. The DNA-binding activity of Ku antigen, analyzed by an electrophoretic mobility shift assay, increased during reperfusion after a short ischemic insult (15 min of occlusion), from which the animals recover neurological function. After severe ischemic injury (60 min of occlusion) and reperfusion that results in permanent paraplegia, Ku DNA binding was reduced. Protein levels of the DNA-PK components—Ku70, Ku80, and DNA-PKcs—were monitored by immunoblotting. After 60 min of occlusion, the amount of DNA-PKcs and the enzyme poly(ADP-ribose) polymerase (PARP) decreased with the same time course during reperfusion. Concurrently 150 and 120 kDa fragments were immunostained by an anti-DNA-PKcs monoclonal antibody. This antibody was shown to cross-react with α-fodrin breakdown products. The 120 kDa fodrin peptide is associated with caspase-3 activation during apoptosis. Both DNA-PKcs and PARP are also substrates for caspase-3-like activities. The results are consistent with a model in which after a short ischemic insult, DNA repair proteins such as DNA-PK are activated. After severe ischemic injury, DNA damage overwhelms repair capabilities, and cell death programs are initiated." @default.
• W2168792406 created "2016-06-24" @default.
• W2168792406 creator A5028934169 @default.
• W2168792406 creator A5034870320 @default.
• W2168792406 creator A5053010120 @default.
• W2168792406 creator A5053246551 @default.
• W2168792406 date "1999-06-15" @default.
• W2168792406 modified "2023-09-24" @default.
• W2168792406 title "Changes in Expression of the DNA Repair Protein Complex DNA-Dependent Protein Kinase after Ischemia and Reperfusion" @default.
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• W2168792406 doi "https://doi.org/10.1523/jneurosci.19-12-04727.1999" @default.
• W2168792406 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6782663" @default.
• W2168792406 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10366606" @default.
• W2168792406 hasPublicationYear "1999" @default.
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