Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach.
Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach.
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DOI：
10.1016/j.freeradbiomed.2011.06.020
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发表时间：
2011-10-15
影响因子：
7.4
通讯作者：
Persidsky, Yuri
中科院分区：
文献类型：
--
作者：
Haorah, James;Floreani, Nicholas A.;Knipe, Bryan;Persidsky, Yuri
关键词：
内皮细胞的氧化损伤会破坏血脑屏障（BBB）的完整性。我们之前已经证明，酒精暴露通过激活 NADPH 氧化酶和诱导型一氧化氮合酶，增加脑内皮细胞中活性氧（ROS、超氧化物和羟自由基）和一氧化氮 (NO) 的水平。我们推测，乙醇暴露中抗氧化系统的损害，例如过氧化氢酶和超氧化物歧化酶 (SOD) 活性的降低，可能会升高内皮细胞中 ROS/NO 的水平，从而导致 BBB 损伤。本研究探讨抗氧化酶活性的稳定是否会导致抗炎剂抑制 ROS 水平。为了解决这个问题，我们确定了乙醇对原代人脑内皮细胞 (hBEC) 中 SOD 和过氧化氢酶活性以及 ROS/NO 生成的动力学特征的影响。我们观察到由于 hBEC 中乙醇的代谢，ROS 和 NO 水平的产生增加。 hBEC 暴露于乙醛（乙醇的主要代谢物）后也发现了类似的增加。乙醇同时增强了 ROS 的产生和抗氧化酶的活性。与过氧化氢酶活性相比，SOD 活性增加的时间要长得多。 SOD 活性和蛋白质水平下降先于氧化剂水平升高。线粒体保护剂乙酰左旋肉碱 (ALC) 和抗炎剂罗格列酮对 SOD 的稳定作用抑制了 ROS 水平，同时 NO 水平略有增加。乙醇暴露后线粒体膜蛋白损伤和膜电位降低表明线粒体损伤。 ALC 阻止了这些更改。我们的研究结果表明，在酒精诱导的血脑屏障氧化应激过程中，氧化剂和抗氧化剂的抵消机制。酶稳定剂的存在有利于 ROS 中和 BBB 的抗氧化氧化还原，表明 NO 对脑血管张力和血管舒张具有潜在的保护机制。
Oxidative damage of the endothelium disrupts the integrity of blood brain barrier (BBB). We have shown before that alcohol exposure increases the levels of reactive oxygen species (ROS, superoxide and hydroxyl radical) and nitric oxide (NO) in brain endothelial cells by activating NADPH oxidase and inducible nitric oxide synthase. We hypothesize that impairment of anti-oxidant systems like reduction of catalase and superoxide dismutase (SOD) activity in ethanol exposure may elevate the levels of ROS/NO in endothelium resulting in BBB damage. The present study examines whether stabilization of antioxidant enzyme activity results in suppression of ROS levels by anti-inflammatory agents. To address this idea, we determined the effects of ethanol on the kinetic profile of SOD and catalase activity and ROS/NO generation in primary human brain endothelial cells (hBECs). We observed an enhanced production of ROS and NO levels due to the metabolism of ethanol in hBECs. Similar increases were found after exposure of hBECs to acetaldehyde, the major metabolite of ethanol. Ethanol simultaneously augmented ROS generation and activity of anti-oxidative enzymes. SOD activity was increased for a much longer period of time as compared to catalase activity. Decline in SOD activity and protein levels preceded elevation of oxidant levels. SOD stabilization by the mitochondria protecting agent, acetyl-L-carnitine (ALC), and anti-inflammatory agent, rosiglitazone, suppressed ROS levels with marginal increase in NO levels. Mitochondrial membrane protein damage and decreased membrane potential after ethanol exposure indicated mitochondrial injury. These changes were prevented by ALC. Our findings suggest the counteracting mechanisms of oxidants and anti-oxidants during alcohol-induced oxidative stress at the BBB. The presence of enzymatic stabilizers favors the ROS neutralizing anti-oxidant redox of the BBB, suggesting an underlying protective mechanism of NO for brain vascular tone and vasodilation.
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影响因子：
3.4
作者：
Griffin, William C., III;Lopez, Marcelo F.;Yanke, Amy B.;Middaugh, Lawrence D.;Becker, Howard C.
通讯作者：
Becker, Howard C.
影响因子：
2.8
作者：
TSUKAMOTO, S;MUTO, T;TAINAKA, H
通讯作者：
TAINAKA, H
影响因子：
5.5
作者：
Hwang, JN;Kleinhenz, DJ;Hart, CM
通讯作者：
Hart, CM
影响因子：
4.7
作者：
Haorah, James;Knipe, Bryan;Persidsky, Yuri
通讯作者：
Persidsky, Yuri
影响因子：
2.3
作者：
Zuba, D;Piekoszewski, W;Parczewski, A
通讯作者：
Parczewski, A