Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is one of the two forms of cell death and occurs under a variety of physiological and pathological conditions. Cells undergoing apoptotic cell death reveal a characteristic sequence of cytological alternations including membrane blebbing and nuclear and cytoplasmic condensation. Early activation of an endonuclease has been previously demonstrated after a transient focal ischemia in the rat brain Charriaut-Marlangue C, Margaill I, Plotkine M, Ben-Ari Y (1995) Early endonuclease activation following reversible focal ischemia. J Cereb Blood Flow Metab 15:385-388). We now show that a significant number of striatal and cortical neurons, exhibited chromatin condensation, nucleus segmentation, and apoptotic bodies increasing with recirculation time, as demonstrated by in situ labeling of DNA breaks in cryostat sections. Apoptotic nuclei were also detected in the horizontal limb diagonal band, accumbens nucleus and islands of Calleja. Several necrotic neurons, in which random DNA fragmentation occurs, were also shown at 6 h recirculation, in the ischemic core. Further investigation with hematoxylin/eosin staining revealed that apoptotic nuclei were present in cells with a large and swelled cytoplasm and in cells with an apparently well-preserved cytoplasm. These two types of cell death were reminiscent of those described in developmental cell death. Our data suggested that apoptosis may contribute to the expansion of the ischemic lesion.
J Cereb Blood Flow Metab 1996 Mar
PMID:Apoptosis and necrosis after reversible focal ischemia: an in situ DNA fragmentation analysis. 859 49

The mechanism by which brief episodes of cerebral ischemia confer protection (tolerance) against subsequent prolonged ischemic challenges remains unclear, but may involve upregulation of cell injury repair capability. The mitochondrion is a key site for the regulation of cell death pathways, and damage to mitochondrial genes has been linked to a number of neurologic diseases and aging. Therefore, the authors examined the response of the DNA base excision repair (BER) pathway in rat brain mitochondria after either brief (tolerance-inducing) or prolonged (injury-producing) focal cerebral ischemia. Brief (30-minute) middle cerebral artery occlusion (MCAO) induced mild oxidative mitochondrial DNA damage and initiated a prolonged (up to 72-hour) activation above control levels of the principal enzymes of the mitochondrial BER pathway, including uracil DNA glycosylase, apurinic/apyrimidinic (AP) endonuclease, DNA polymerase-gamma, and DNA ligase. In contrast, prolonged (100-minute MCAO) ischemia induced more substantial mitochondrial oxidative DNA damage whereas elevation of BER activity was transient (approximately 1 hour), declining to less than control levels over the course of 4 to 72 hours. These data reveal the differences in BER capacity after brief or prolonged ischemia, which may contribute to the neuron's ability to resist subsequent ischemic insults.
J Cereb Blood Flow Metab 2003 Jan
PMID:Upregulation of mitochondrial base-excision repair capability within rat brain after brief ischemia. 1250 94

The development of ischemic tolerance in the brain, whereby a brief period of sublethal 'preconditioning' ischemia attenuates injury from subsequent severe ischemia, may involve the activation of multiple intracellular signaling events that promote neuronal survival. In this study, the potential role of inducible DNA base-excision repair (BER), an endogenous adaptive response that prevents the detrimental effect of oxidative DNA damage, has been studied in the rat model of ischemic tolerance produced by three episodes of ischemic preconditioning (IP). This paradigm of IP, when applied 2 and 5 days before 2-h middle cerebral artery occlusion (MCAO), significantly decreased infarct volume in the frontal-parietal cortex 72 h later. Correlated with this protective effect, IP markedly attenuated the nuclear accumulations of several oxidative DNA lesions, including 8-oxodG, AP sites, and DNA strand breaks, after 2-h MCAO. Consequently, harmful DNA damage-responsive events, including NAD depletion and p53 activation, were reduced during postischemic reperfusion in preconditioned brains. The mechanism underlying the decreased DNA damage in preconditioned brain was then investigated by measuring BER activities in nuclear extracts. Beta-polymerase-mediated BER activity was markedly increased after IP, and this activation occurred before (24 h) and during the course of ischemic tolerance (48 to 72 h). In similar patterns, the activities for AP site and 8-oxodG incisions were also upregulated after IP. The upregulation of BER activities after IP was likely because of increased expression of repair enzymes beta-polymerase, AP endonuclease, and OGG1. These results suggest that the activation of the BER pathway may contribute to IP-induced neuroprotection by enhancing the repair of endogenous oxidative DNA damage after ischemic injury.
J Cereb Blood Flow Metab 2006 Feb
PMID:Ischemic preconditioning in the rat brain enhances the repair of endogenous oxidative DNA damage by activating the base-excision repair pathway. 1600 Oct 17