Oxidative DNA Damage and Repair in Rat Kidney

小行星9631166 许多化学反应发生在受氧损失和在恢复血流时发生的再氧合影响的细胞中。这些细胞反应的一个副产品是形成一种高活性形式的氧，称为氧自由基。氧自由基导致DNA（遗传物质）发生改变，这可能会影响细胞执行正常生物功能的能力。由于DNA结构的单一变化可能是有害的，因此在细胞水平上进化出多种修复DNA的机制也就不足为奇了。在这个提议中概述的实验被设计来检查一种酶，氧化还原内切酶，修复DNA的氧化损伤。将在缺氧（缺血）肾脏和再氧再灌注）大鼠肾脏中定量该酶的水平，并与未受损组织中该蛋白质的水平进行比较。具体而言，将检查组织的1）氧化DNA修复酶活性水平; 2）氧化DNA损伤的细胞修复;和3）在缺血或再氧事件期间形成的特异性氧化DNA碱基损伤水平。这些实验的结果将为修复氧化DNA损伤的细胞机制的调节和组织承受氧化应激条件的能力提供新的见解。

9631166 Gallagher A number of chemical reactions occur in cells affected by the loss of oxygen and by reoxygenation which occurs upon resumption of blood flow. One by-product of these cellular reactions is the formation of a highly reactive form of oxygen, known as an oxygen free radical. Oxygen free radicals produce alterations in DNA, the genetic material, which may affect the ability of cells to carry out their normal biological functions. Since a single change in DNA structure may be harmful, it is not surprising that a diverse array of mechanisms for repairing DNA evolved at the cellular level. The experiments outlined in this proposal are designed to examine an enzyme, redoxyendonuclease, that repairs oxidative damage to DNA. The levels of this enzyme will be quantified in the oxygen-deprived (ischemic) kidney and the reoxygenated reperfused) rat kidney and compared to the levels of this protein in the undamaged tissue. Specifically, the tissue will be examined for 1) the level of the oxidative DNA repair enzyme activity; 2) the cellular repair of oxidized DNA damage; and 3) the levels of specific oxidized DNA base damages formed during the ischemic or reoxygenanon event. Results from these experiments will provide new insights into the regulation of the cellular mechanisms that repair oxidative DNA damage and the ability of tissues to withstand conditions of oxidant stress.