MODIFIED HEMOGLOBINS AS A SOURCE OF ACTIVATED OXYGEN SPECIES

非囊化、非络合、化学修饰的血红蛋白可作为 “生物芬顿试剂”，有可能催化 活性氧种的产生。正在进行的研究的要点： 1)血红蛋白驱动的羟基自由基生成：到目前为止，结果是 表明修饰的和未修饰的血红蛋白在存在 过氧化氢产生系统(黄嘌呤/黄嘌呤氧化酶)可以 确实促进了羟基自由基的形成。 2)血红蛋白的Fenton型氧化还原反应： 公认的血红蛋白参与Fenton样反应的影响是 氧合血红蛋白与高铁血红蛋白的相互转化。 A.我们监测了三种改良的高铁血红蛋白的形成 在存在的情况下延长时间内的血红蛋白 酶促和非酶促产生的H202。 B.在其他实验中，这些血红蛋白的铁(MET)形式 被NAD(P)H有氧还原。修饰的血红蛋白显示 NAD(P)H的还原程度和还原速率均有显著差异。 C.当上述简单反应体系扩展到包括苯胺时， 对氨基苯酚是在类似单加氧酶的反应中产生的。已修改 当加入到这个系统中时，血红蛋白与它们的单加氧酶有明显的不同。 导致苯胺羟基化的活性。 计划进行一些体内和体内研究，以便继续 检测血红蛋白介导的氧自由基的产生并确定 这些自由基如何加重缺血动物的“再灌注损伤” 模特，

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,