Reactive oxygen species at phospholipid bilayers: Distribution, mobility and permeation
Reactive oxygen species at phospholipid bilayers: Distribution, mobility and permeation
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DOI：
10.1016/j.bbamem.2013.09.016
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发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Cordeiro, Rodrigo M.
中科院分区：
文献类型：
--
作者：
Cordeiro, Rodrigo M.
活性氧（reactive oxygen species，ROS）参与氧化还原信号传导、衰老、癌变和神经退行性变等生物化学过程。虽然生物膜是活性氧攻击的目标，但对其特定相互作用的作用知之甚少。在这里，分子动力学模拟，以确定在膜-水界面的各种活性氧物种的分布，流动性和停留时间。模拟结果表明，分子氧（O-2）积累在膜内部。讨论了这一结果对单线态氧（O-2（-））的适用性。相反，超氧化物（Cc）自由基和过氧化氢（H2 O2）留在水相。羟基（HO）和过氧化氢（HO 2）自由基都能够深入渗透到脂质头基区域。由于膜的流动性和无序性，这些自由基可以沿着脂烃链沿着进入潜在的过氧化位点，而不必克服渗透自由能屏障。引人注目的是，HO 2自由基是一个数量级更集中在头基区域比在水中，这意味着在HO 2和O之间的酸碱平衡的大位移。与O-2相比，HO和HO 2自由基在膜上的横向迁移率较低。模拟结果表明，在头基区域HO自由基周围的氢键网络中存在间歇性中断。预计这种效应对HO扩散中涉及的H-转移机制是不利的。脂质过氧化和膜抗氧化剂的有效性的影响进行了评价。(C)2013 Elsevier B. V.保留所有权利。
Reactive oxygen species (ROS) are involved in biochemical processes such as redox signaling, aging, carcinogenesis and neurodegeneration. Although biomembranes are targets for reactive oxygen species attack, little is known about the role of their specific interactions. Here, molecular dynamics simulations were employed to determine the distribution, mobility and residence times of various reactive oxygen species at the membrane-water interface. Simulations showed that molecular oxygen (O-2) accumulated at the membrane interior. The applicability of this result to singlet oxygen (O-2(-)) was discussed. Conversely, superoxide (Cc) radicals and hydrogen peroxide (H2O2) remained at the aqueous phase. Both hydroxyl (HO) and hydroperoxyl (HO2) radicals were able to penetrate deep into the lipid headgroups region. Due to membrane fluidity and disorder, these radicals had access to potential peroxidation sites along the lipid hydrocarbon chains, without having to overcome the permeation free energy barrier. Strikingly, HO2 radicals were an order of magnitude more concentrated in the headgroups region than in water, implying a large shift in the acid-base equilibrium between HO2 and O. In comparison with O-2, both HO and HO2 radicals had lower lateral mobility at the membrane. Simulations revealed that there were intermittent interruptions in the H-bond network around the HO radicals at the headgroups region. This effect is expected to be unfavorable for the H-transfer mechanism involved in HO diffusion. The implications for lipid peroxidation and for the effectiveness of membrane antioxidants were evaluated. (C) 2013 Elsevier B.V. All rights reserved.