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镉对贻贝线粒体氧化应激和 NADH 震荡的影响。

Influence of cadmium on oxidative stress and NADH oscillations in mussel mitochondria.

机构信息

Aquatic Contaminants Research Division, Environment and Climate Change Canada, 105 McGill, Montreal, Québec H2Y 2E7, Canada.

Aquatic Contaminants Research Division, Environment and Climate Change Canada, 105 McGill, Montreal, Québec H2Y 2E7, Canada.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2019 Feb;216:60-66. doi: 10.1016/j.cbpc.2018.11.005. Epub 2018 Nov 7.

DOI:10.1016/j.cbpc.2018.11.005
PMID:30414481
Abstract

Biological organisms evolved to take advantage of recurring environmental factors which enabled them to assimilate and process metabolic energy for survival. Mitochondria display non-linear oscillations in NADH levels (i.e. wave behavior) that result from the balance between NADH production (aerobic glycolysis) and oxidation for ATP synthesis. The purpose of this study was to examine the effects of cadmium (Cd) on mitochondrial NADH oscillations in quagga mussels Dreissena bugensis exposed to 50 and 100 μg/L CdCl2 for 7 days at 15 °C. Metallothionein (MT) levels, thioredoxin reductase (TrxR) activity and NADH oxidation rate were also determined, as were oscillations in NADH and the formation of dissipative structures (turbidity), in isolated mitochondria suspensions. The results show that exposure to Cd readily induced MT levels at both concentrations tested and that TrxR and NADH oxidase activity was induced at 100 μg/L Cd only. In control mussels, NADH levels oscillated in mitochondria suspensions with a natural period of 2 to 2.5 min for up to 40 min. Exposure to Cd increased the complexity of the frequency profile of NADH oscillations and reduced the amplitudes of the natural signal with a period of 2 to 2.5 min. The formation of dissipative structures decreased in response to a Cd concentration of 100 μg/L but increased at a level of 50 μg/L. The amplitudes at the natural frequency were significantly correlated with NADH oxidase activity (r = -0.91) and with the formation of dissipative structures (r = -0.59). We conclude that Cd could alter the natural frequency in oscillations of NADH in mitochondria, thereby contributing to an increase in NADH oxidation rate and disruption of the spatial organization of mitochondria in suspension. In conclusion, changes in the wave behavior of NADH in mitochondria are proposed as a novel biomarker of toxicity in aquatic organisms.

摘要

生物有机体进化为了利用可重复出现的环境因素,这些因素使它们能够同化和处理代谢能以维持生存。线粒体显示出 NADH 水平的非线性振荡(即波行为),这是由于 NADH 产生(有氧糖酵解)和氧化以合成 ATP 之间的平衡所致。本研究的目的是检查镉(Cd)对暴露于 50 和 100μg/L CdCl2 下的斑马贻贝 Dreissena bugensis 线粒体 NADH 振荡的影响,温度为 15°C,持续 7 天。还测定了金属硫蛋白(MT)水平、硫氧还蛋白还原酶(TrxR)活性和 NADH 氧化速率,以及 NADH 振荡和耗散结构(浊度)的形成,在分离的线粒体悬浮液中。结果表明,在两种测试浓度下,镉容易诱导 MT 水平升高,而仅在 100μg/L Cd 下诱导 TrxR 和 NADH 氧化酶活性。在对照贻贝中,NADH 水平在 2 到 2.5 分钟的自然周期内在线粒体悬浮液中振荡,长达 40 分钟。暴露于 Cd 增加了 NADH 振荡的频率谱的复杂性,并降低了具有 2 到 2.5 分钟自然周期的天然信号的幅度。随着 Cd 浓度为 100μg/L,耗散结构的形成减少,但在 50μg/L 时增加。在自然频率下的幅度与 NADH 氧化酶活性(r=-0.91)和耗散结构的形成(r=-0.59)显著相关。我们得出结论,Cd 可以改变线粒体中 NADH 振荡的自然频率,从而导致 NADH 氧化速率增加和线粒体在悬浮液中的空间组织受到破坏。总之,提出了线粒体中 NADH 波行为的变化作为水生生物毒性的新型生物标志物。

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