Raess B U, Keenan C E, McConnell E J
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Evansville 47712, USA.
Biochem Biophys Res Commun. 1997 Jun 27;235(3):451-4. doi: 10.1006/bbrc.1997.6819.
Structural and functional alterations of cell membranes caused by free radicals leading to lipid peroxidation and increases in intracellular Ca2+ concentrations have been implicated in atherogenesis. The objective of this study was to directly measure the effects of a major aldehydic lipid peroxidation product, 4-OH-nonenal (HNE), on plasma membrane Ca2+ regulatory mechanisms. This was attained by measuring passive Ca2+ permeability, primary active Ca2+-transport, and (Ca2+ + Mg2+)-ATPase activity in a human red cell model system. Using this three-pronged approach it could be shown that HNE increases passive Ca2+ permeability significantly beyond the typically low basal flux, while at the same time inhibiting the active Ca2+ extrusion pump and associated (Ca2+ + Mg2+)-ATPase activity. We conclude that this deleterious combination of effects by HNE in this plasma membrane model system may be indicative of plasma membrane changes in cells directly involved in atheroma formation and thus may represent causative factors in the early stages of atherogenesis.
自由基导致的细胞膜结构和功能改变，进而引发脂质过氧化以及细胞内钙离子浓度升高，这与动脉粥样硬化的发生有关。本研究的目的是直接测定主要醛类脂质过氧化产物4-羟基壬烯醛（HNE）对质膜钙离子调节机制的影响。这是通过在人红细胞模型系统中测量被动钙离子通透性、原发性主动钙离子转运以及（钙离子 + 镁离子）-ATP酶活性来实现的。采用这种三管齐下的方法可以表明，HNE显著增加了被动钙离子通透性，使其远超通常较低的基础通量，同时抑制了主动钙离子外排泵以及相关的（钙离子 + 镁离子）-ATP酶活性。我们得出结论，在这个质膜模型系统中，HNE的这种有害效应组合可能表明直接参与动脉粥样硬化斑块形成的细胞中的质膜发生了变化，因此可能代表动脉粥样硬化发生早期的致病因素。
