钒化合物通过不同方式刺激线粒体活性氧生成

doi:10.5246/jcps.2011.05.063

钒化合物通过不同方式刺激线粒体活性氧生成

施喆, 刘会雪^*, 杨晓达^*

北京大学医学部天然药物及仿生药物国家重点实验室; 药学院化学生物学系, 北京 100191

收稿日期:2011-05-11 修回日期:2011-07-10 出版日期:2011-09-20 发布日期:2011-09-20
通讯作者: 刘会雪*, 杨晓达*

Vanadium stimulates mitochondrial ROS production in different ways

Zhe Shi, Hui-Xue Liu^*, Xiao-Da Yang^*

State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-05-11 Revised:2011-07-10 Online:2011-09-20 Published:2011-09-20
Contact: Hui-Xue Liu*, Xiao-Da Yang*

摘要/Abstract

摘要： 钒化合物在癌症及糖尿病治疗中显示出其潜在的可能而受到人们的关注, 但是其毒性限制了其作为药物的进一步发展。已有研究表明钒通过影响线粒体功能诱导的氧化应激是钒化合物毒性的主要原因。本工作主要考察了两种钒化合物-偏钒酸钠和乙酰丙酮氧钒对线粒体活性氧产生和呼吸链复合体活性的影响。结果表明, 钒化合物依其化学物种的不同而对活性氧和复合体活性以不同的方式产生影响。偏钒酸钠抑制线粒体复合体I和II的活性, 同时在低浓度范围内促进活性氧的产生。而氧钒化合物则促进复合体II活性, 同时促进复合体I相关途径的电子漏。本工作为研究钒化合物作为抗糖尿病药物毒性提供了新的结果。

关键词: 钒物种, 活性氧生成, 复合体活性, 线粒体

Abstract:

Vanadium compounds show potential in diabetes and cancer treatment, although the toxicity remains a great concern. Previous studies have shown that vanadium-induced oxidative stress affecting mitochondrial function is intensively responsible for the toxicity. In this work, we investigated the effects of the vanadium compounds sodium metavanadate (NaVO3) and vanadyl acetylacetonate (VO(acac)2) on mitochondrial ROS generation and respiratory complex activities. The experimental results showed that vanadium compounds affected the ROS generation and complex activities in different patterns depending on the chemical species. NaVO3 inhibited mitochondrial complexes I and II activities and stimulated ROS generation at low concentration range; while VO(acac)2 promoted complex II activity but resulted in electron leakage from the complex I-involved pathway. The present results provide new evidence for understanding the toxicity of antidiabetic vanadium compounds.

Key words: Vanadium species, ROS generation, Respiratory complex activity, Mitochondria

中图分类号:

R962.1

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 20671008/20971008).
^*Corresponding author. Tel.: 86-10-82805611; Fax: 86-10-62015584

施喆, 刘会雪^*, 杨晓达^*. 钒化合物通过不同方式刺激线粒体活性氧生成[J]. , DOI: 10.5246/jcps.2011.05.063.

Zhe Shi, Hui-Xue Liu^*, Xiao-Da Yang^*. Vanadium stimulates mitochondrial ROS production in different ways[J]. , DOI: 10.5246/jcps.2011.05.063.

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