FREE-RADICAL DAMAGE TO PROTEIN AND DNA - MECHANISMS INVOLVED AND RELEVANT OBSERVATIONS ON BRAIN UNDERGOING OXIDATIVE STRESS
FREE-RADICAL DAMAGE TO PROTEIN AND DNA - MECHANISMS INVOLVED AND RELEVANT OBSERVATIONS ON BRAIN UNDERGOING OXIDATIVE STRESS
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DOI：
10.1002/ana.410320706
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发表时间：
1992-01-01
影响因子：
11.2
通讯作者：
CARNEY, JM
中科院分区：
文献类型：
--
作者：
FLOYD, RA;CARNEY, JM
铁介导蛋白质和DNA的损伤。损伤机制不仅涉及铁，而且还涉及氧自由基中间体。对DNA的氧化损伤不仅导致链断裂，还导致特异性碱基加合物的形成，例如8-羟基-2 '-脱氧鸟苷。氧化损伤也使某些酶失活，如谷氨酰胺合成酶。评估组织氧化损伤的新方法，包括水杨酸羟基化作为羟基自由基通量的指标以及对蛋白质和DNA的特异性损伤的定量，已经产生的结果清楚地表明，蒙古沙鼠脑缺血/再灌注损伤涉及氧化损伤事件。沙鼠和人脑的衰老也与氧化损伤增加有关。最近的新观察表明，自旋捕获剂苯基α-叔丁基硝酮（PBN）在沙土鼠脑缺血/再灌注损伤过程中提供保护。我们还表明，在衰老过程中，脑的氧化损伤是减少慢性管理PBN。PBN的作用机制可能与其捕获特定的自由基有关，自由基引发一系列氧化事件，最终导致组织损伤。
Iron mediates damage to proteins and DNA. The mechanisms of damage not only involve iron but also oxygen free radical intermediates. Oxidative damage to DNA causes not only strand breaks, but also formation of specific base adducts, such as 8-hydroxy-2'-deoxyguanosine. Oxidative damage also inactivates certain enzymes such as glutamine synthetase. Novel methods of assessing oxidative damage to tissue, including quantitation of salicylate hydroxylation as an index of hydroxyl free radical flux as well as specific lesions to proteins and DNA, have yielded results that clearly show that ischemia/reperfusion injury to mongolian gerbil brain involves oxidatively damaging events. Aging in gerbil as well as human brain is also associated with increased oxidative damage. Recent novel observations have shown that the spin-trapping agent phenyl alpha-tert-butylnitrone (PBN) offers protection in gerbil brain during ischemia/reperfusion injury. We also show that oxidative damage to brain during aging is decreased by chronic administration of PBN. The mechanism of action of PBN may be related to its trapping of specific free radicals, which triggers a cascade of oxidative events that eventually lead to tissue injury.