[Frontiers in Bioscience 12, 1852-1862, January 1, 2007] 1852 Impaired DNA repair via the base-excision repair pathway after focal ischemic brain injury: a protein phosphorylation- dependent mechanism reversed by hypothermic neuroprotection
نویسندگان
چکیده
1. Abstract 2. Introduction 3. Materials and methods 3.1. Rat model of focal cerebral ischemia 3.2. Measurement of overall BER activity 3.3. Measurement of AP endonuclease activity 3.4. Measurement of DNA polymerase-beta activity 3.5. Western blot analysis 3.6. Quantitative measurement of AP sites in nuclear DNA 3.7. Detection of DNA single-strand breaks 3.8. Statistical analysis 4. Results 4.1. Reduction in BER activities during post-ischemic reperfusion 4.2. Reduction in BER activities independent of altered expression of repair enzymes 4.3. Phosphorylation-mediated inactivation of BER enzymes after ischemia 4.4. Post-ischemic hypothermia restores BER activity 4.5. Post-ischemic hypothermia attenuates oxidative DNA damage 5. Discussion 6. Acknowledgments 7. References
منابع مشابه
Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia.
Inducible DNA repair via the base-excision repair pathway is an important prosurvival mechanism activated in response to oxidative DNA damage. Elevated levels of the essential base-excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 correlate closely with neuronal survival against ischemic insults, depending on the CNS region, protective treatments, and de...
متن کاملCellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair.
BACKGROUND AND PURPOSE NAD(+) is an essential cofactor for cellular energy production and participates in various signaling pathways that have an impact on cell survival. After cerebral ischemia, oxidative DNA lesions accumulate in neurons because of increased attacks by ROS and diminished DNA repair activity, leading to PARP-1 activation, NAD(+) depletion, and cell death. The objective of this...
متن کاملMild hypothermia diminishes oxidative DNA damage and pro-death signaling events after cerebral ischemia: a mechanism for neuroprotection.
Mild hypothermia, applied either during or soon after cerebral ischemia, has been shown to confer robust neuroprotection against brain injury in experimental stroke and in patients recovering from cardiac arrest. However, the mechanism underlying hypothermic neuroprotection is not completely understood. In this study, the effect of mild hypothermia on the induction of oxidative DNA damage, an e...
متن کاملInducible repair of oxidative DNA lesions in the rat brain after transient focal ischemia and reperfusion.
To determine the role of oxidative DNA damage and repair in brain injury after focal ischemia and reperfusion, the authors investigated DNA base damage and DNA base excision repair (BER) capacity, the predominant repair mechanism for oxidative DNA lesions, in the rat model of temporary middle cerebral artery occlusion. Contents of 8-hydroxyl-2'-deoxyguanosine (8-oxodG) and apurinic/apyrimidinic...
متن کاملEarly decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice.
BACKGROUND AND PURPOSE DNA damage and the DNA repair mechanism are known to be involved in ischemia/reperfusion injury in the brain. The x-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation b...
متن کامل