Lamba O P, Borchman D, Garner W H
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Research Institute 40292.
Free Radic Biol Med. 1994 May;16(5):591-601. doi: 10.1016/0891-5849(94)90059-0.
The role of free-radical-induced lipid peroxidation (LPO) in relation to lens opacity is investigated using Fourier transform infrared spectroscopy. Phospholipids extracted from nuclear and cortical regions of the rabbit lens membranes are subjected to oxidative-damage induced by hydrogen peroxide and Fe2+/Fe3+ cations. Vibrational data suggest a homolytic decomposition of the unsaturated membrane hydrocarbon chains at cis-double bonds, as well as structural modifications at the carbonyl and phosphate-oxygen sites of the fiber cell membranes upon metal oxidation. This is also evident from a substantial induction of the carbonyl groups and a significant dephosphorylation of the phosphate groups in lens phospholipids. These covalent modifications and/or alterations of the carbonyl and phosphate groups, and specificity of certain vibrational modes only to iron oxidation, may serve as a diagnostic probe of the metal-catalyzed LPO in lens membranes. Despite covalent modifications of the hydrophilic part of the lens membranes, hydrocarbon chain region remains largely intact at physiological concentrations of hydrogen peroxide. However, at elevated concentrations of hydrogen peroxide, a substantial breakdown of the acyl chains occurs. Striking similarities observed between the spectral features of the oxidized rabbit lens phospholipids and those of the cataractous human lenses suggest that the mechanism and pathways of lipid oxidation in model animal membranes and in human lenses are similar. Differences in the nuclear or cortical regions are also evident upon metal oxidation. Nuclear lipids experience increased effects of the metal oxidation compared to cortical lipids. Both the nuclear or the cortical lipids indicate effective penetration of the bilayer water creating segregated membrane domains, possibly through breakdown of headgroup-specific lipid-water interactions. This could effectively alter the lens membrane permeability and fluidity, rendering it susceptible to a host of toxic oxidants present in the eye. These findings also demonstrate that LPO can lead to acyl chain degradation that may effectively derange the lens membrane function, which could be a contributing factor in cataractogenesis.
利用傅里叶变换红外光谱研究自由基诱导的脂质过氧化（LPO）与晶状体混浊的关系。从兔晶状体膜的核区和皮质区提取的磷脂受到过氧化氢和Fe2+/Fe3+阳离子诱导的氧化损伤。振动数据表明，不饱和膜烃链在顺式双键处发生均裂分解，以及在金属氧化时纤维细胞膜的羰基和磷酸氧位点发生结构修饰。这也明显体现在晶状体磷脂中羰基的大量诱导和磷酸基团的显著去磷酸化。这些羰基和磷酸基团的共价修饰和/或改变，以及某些振动模式仅对铁氧化的特异性，可作为晶状体膜中金属催化LPO的诊断探针。尽管晶状体膜的亲水部分发生了共价修饰，但在生理浓度的过氧化氢下，烃链区域基本保持完整。然而，在过氧化氢浓度升高时，酰基链会大量分解。氧化兔晶状体磷脂的光谱特征与白内障患者晶状体的光谱特征之间存在惊人的相似性，这表明模型动物膜和人晶状体中脂质氧化的机制和途径相似。金属氧化后，核区或皮质区的差异也很明显。与皮质脂质相比，核脂质受到金属氧化的影响更大。核脂质或皮质脂质都表明双层水有效渗透，形成分离的膜结构域，可能是通过破坏头基特异性脂质-水相互作用。这可能有效地改变晶状体膜的通透性和流动性，使其易受眼中存在的多种有毒氧化剂的影响。这些发现还表明，LPO可导致酰基链降解，从而有效地扰乱晶状体膜功能，这可能是白内障发生的一个促成因素。
