Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse.
Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse.
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DOI：
10.1155/2016/1089364
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发表时间：
2016
影响因子：
--
通讯作者：
Ali SS
中科院分区：
文献类型：
--
作者：
Abdel-Rahman EA;Mahmoud AM;Aaliya A;Radwan Y;Yasseen B;Al-Okda A;Atwa A;Elhanafy E;Habashy M;Ali SS
细胞氧化还原稳态的破坏与多种病理状况和衰老有关。决定这种平衡的一个基本因素是线粒体介导的完全氧还原成水与线粒体不完全还原成超氧自由基和 NADPH 氧化酶 (NOX) 酶活性之间的比率。在这里，我们使用高分辨率呼吸测量法结合荧光或电化学感觉，确定了线粒体以及 NOX 依赖性的耗氧率，并与新鲜分离的突触体中 H2O2 的产生并行。我们的结果表明，虽然突触线粒体表现出明显更高的呼吸活动（根据线粒体呼吸状态，比 NOX 耗氧量高 8-82 倍），但 NADPH 依赖性耗氧量与更多的 H2O2 产生相关（NOX-H2O2 高 6-7 倍）。我们还表明，就消耗的氧气而言，虽然突触线粒体在 NAD+ 相关的静息期间“泄漏”0.71% ± 0.12 H2O2，在 NAD+ 相关的主动呼吸期间“泄漏”0.21% ± 0.04，在 FAD+ 相关的主动呼吸期间“泄漏”0.07% ± 0.02，但 NOX 将 38% ± 13 的 O2 转化为 H2O2。我们的结果表明，NOX 而不是线粒体是突触 H2O2 的主要来源。本方法可能有助于识别神经元中各种生理和病理过程背后的氧化还原调节突触因子。
Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2 generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory. Our results indicate that although synaptic mitochondria exhibit substantially higher respiratory activities (8–82-fold greater than NOX oxygen consumption depending on mitochondrial respiratory state), NADPH-dependent oxygen consumption is associated with greater H2O2 production (6-7-fold higher NOX-H2O2). We also show that, in terms of the consumed oxygen, while synaptic mitochondria “leaked” 0.71% ± 0.12 H2O2 during NAD+-linked resting, 0.21% ± 0.04 during NAD+-linked active respiration, and 0.07% ± 0.02 during FAD+-linked active respiration, NOX converted 38% ± 13 of O2 into H2O2. Our results indicate that NOX rather than mitochondria is the major source of synaptic H2O2. The present approach may assist in the identification of redox-modulating synaptic factors that underlie a variety of physiological and pathological processes in neurons.
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影响因子：
3.7
作者：
Zhang QG;Laird MD;Han D;Nguyen K;Scott E;Dong Y;Dhandapani KM;Brann DW
通讯作者：
Brann DW
影响因子：
7.4
作者：
Mishin, Vladimir;Gray, Joshua P.;Heck, Diane E.;Laskin, Debra L.;Laskin, Jeffrey D.
通讯作者：
Laskin, Jeffrey D.
DOI：
10.1016/j.jamcollsurg.2015.08.003
发表时间：
2015-11-01
影响因子：
5.2
作者：
Li, Yuntong;Xia, Yong;Shen, Feng
通讯作者：
Shen, Feng
影响因子：
5.2
作者：
Starkov AA
通讯作者：
Starkov AA
影响因子：
4.6
作者：
Breckwoldt MO;Armoundas AA;Aon MA;Bendszus M;O'Rourke B;Schwarzländer M;Dick TP;Kurz FT
通讯作者：
Kurz FT