MODIFIED HEMOGLOBINS AS A SOURCE OF ACTIVATED OXYGEN SPECIES

非胶囊化的、非复合的、化学修饰的血红蛋白可以作为 “生物芬顿试剂”，具有催化 产生活性氧物质。正在进行的研究的重点： 1)血红蛋白驱动的羟基自由基生成：迄今为止的结果 表明修饰的和未修饰的血红蛋白在 过氧化氢生成系统（黄嘌呤/黄嘌呤氧化酶）可以 确实促进羟基自由基形成。 2)血红蛋白的芬顿型氧化还原反应：一种新的研究方法 血红蛋白参与芬顿样反应的公认效应是 氧合血红蛋白转化为高铁血红蛋白，反之亦然。 a.我们已经监测了高铁血红蛋白的形成，从三个修改 血红蛋白在一个较长的时间内，在存在 酶促和非酶促产生H2 O2。 B.在另一组实验中，这些血红蛋白的铁（met）形式 NAD（P）H可使需氧性降低。修饰的血红蛋白显示出 NAD（P）H降低的程度和速率均有明显差异。 C.当上述简单反应体系扩展到包括苯胺时， 在单加氧酶样反应中产生帕拉氨基苯酚。改性 血红蛋白当加入到该系统中时，它们的单加氧酶 活性导致苯胺的羟基化。 计划进行一些体内和体内研究，以继续 检查血红蛋白介导的氧自由基产生，并确定 这些自由基如何加重缺血动物的“再灌注损伤” 模型，

Non-capsulated, non-complexed, chemically modified hemoglobin may act as a "Biological Fenton Reagent", having the potential to catalyze the production of activated oxygen species. Highlights of ongoing studies: 1) Hemoglobin driven hydroxyl radical generation: Results so far have indicated that both modified and unmodified hemoglobins in the presence of a hydrogen peroxide-generating system (Xanthine/Xanthine oxidase) can indeed promote hydroxyl radical formation. 2)Fenton Type Oxidation-Reduction reactions of hemoglobin:One of the recognized effects of hemoglobin involvement in a fenton-like reaction is the transformation of oxyhemoglobin to methemoglobin and vice versa. a. We have monitored methemoglobin formation from three modified hemoglobins over an extended period of time in the presence of enzymatically and nonenzymatically generated H202. b. In other sets of experiments, the ferric (met) form of these hemoglobins were aerobically reduced by NAD(P)H. The modified hemoglobins exhibited appreciable difference in both the degree and rate of reduction by NAD(P)H. c. When the above simple reaction system is expanded to include aniline, para aminophenol is generated in a monoxygenase-like reaction. Modified hemoglobins when added to this system differ appreciably their monoxygenase activity which brought about the hydroxylation of aniline. A number of in and in vivo studies are planned in order to continue to examine the hemoglobin-mediated oxygen radical generation and to determine how these radicals may aggravate "reprefusion injury" in an ischemic animal model,