Generation of reactive oxygen species by hydroxypyridone compound/iron complexes.

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Keiko Murakami, Masataka Yoshino
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引用次数: 5

Abstract

Objectives: Prooxidant properties of iron-binding hydroxypyridone compounds including deferiprone and mimosine were analyzed. Methods: Hydroxypyridone/iron-dependent production of reactive oxygen species was evidenced by the inactivation of aconitase, the most sensitive enzyme to oxidative stress in permeabilized yeast cells. Results and Discussion: Deferiprone and mimosine produced reactive oxygen species in the presence of ferrous sulfate. The inactivation required sodium azide the inhibitor of catalase, and addition of TEMPOL, a scavenger of superoxide radical, protected aconitase from the inactivation, suggesting that the superoxide radical produced from the hydroxypyridone/iron complex is responsible for the inactivation of aconitase. A principal role of superoxide radical was further supported by the finding that the hydroxypyridone/iron complex can inactivate aconitase in the presence of cyanide the inhibitor of superoxide dismutase. Deferiprone and mimosine stimulated the Fe2+ oxidation, resulting in the one-electron reduction of oxygen to form superoxide anion, which can inactivate aconitase by oxidizing the prosthetic iron-sulfur cluster. Mimosine further stimulated the ascorbate/iron-dependent formation of 8-hydroxy-2'-deoxyguanosine in DNA. Conclusion: Biological toxicity of mimosine and deferiprone reported previously can be accounted for by the prooxidant properties of hydroxypyridone compounds: coordination complex with iron generates reactive oxygen species resulting in the disturbance of mitochondrial energy metabolism and DNA damage.

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羟基吡啶酮/铁配合物生成活性氧的研究。
目的:分析铁结合羟基吡啶酮类化合物的抗氧化性能。方法:通过对氧化应激最敏感的乌头酶失活,证实了羟基吡啶酮/铁依赖性活性氧的产生。结果与讨论:在硫酸亚铁存在的情况下,去铁蛋白和氨基葡萄糖产生活性氧。乌头酶的失活需要叠氮化钠(过氧化氢酶的抑制剂)和TEMPOL(超氧化物自由基的清除剂)的加入,这表明羟基吡啶酮/铁络合物产生的超氧化物自由基是乌头酶失活的原因。羟基吡啶酮/铁络合物可以在超氧化物歧化酶抑制剂氰化物存在的情况下灭活乌头酶,这一发现进一步支持了超氧化物自由基的主要作用。去铁素和氨基氨刺激Fe2+氧化,导致氧单电子还原形成超氧阴离子,通过氧化假体铁硫簇使乌头酶失活。蜜胺进一步刺激DNA中8-羟基-2'-脱氧鸟苷的抗坏血酸/铁依赖性形成。结论:羟基吡啶酮类化合物的促氧化特性可以解释先前报道的氨莫辛和去铁酮的生物毒性:与铁配合物产生活性氧,导致线粒体能量代谢紊乱和DNA损伤。
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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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