Neto Antenor J P, Cordeiro Rodrigo M
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, CEP 09210-580 Santo André, SP, Brazil.
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, CEP 09210-580 Santo André, SP, Brazil.
Biochim Biophys Acta. 2016 Sep;1858(9):2191-2198. doi: 10.1016/j.bbamem.2016.06.018. Epub 2016 Jun 24.
Non-enzymatic lipid peroxidation may change biomembrane structure and function. Here, we employed molecular dynamics simulations to study the effects of either phospholipid or cholesterol peroxidation individually, as well as the combined peroxidation of both components. When lipids were peroxidized, the generated OOH groups migrated to the membrane surface and engaged in H-bonds with each other and the phospholipid carbonyl ester groups. It caused the sn-2 acyl chains of phospholipid hydroperoxides to bend and the whole sterol backbone of cholesterol hydroperoxides to tilt. When phospholipids were kept intact, peroxidation of the sterol backbone led to a partial degradation of its condensing and ordering properties, independently of the position and isomerism of the OOH substitution. However, even in massively peroxidized membranes in which all phospholipids and cholesterol were peroxidized, the condensing and ordering properties of the sterol backbone were still significant. The possible implications for the formation of membrane lateral domains were discussed. Cholesterol peroxyl radicals were also investigated and we found that the OO groups did not migrate to the headgroups region.
非酶促脂质过氧化可能会改变生物膜的结构和功能。在此，我们采用分子动力学模拟分别研究磷脂或胆固醇过氧化的影响，以及这两种成分的联合过氧化作用。当脂质发生过氧化时，生成的OOH基团迁移至膜表面，并彼此之间以及与磷脂羰基酯基团形成氢键。这导致磷脂氢过氧化物的sn-2酰基链发生弯曲，胆固醇氢过氧化物的整个甾醇骨架发生倾斜。当磷脂保持完整时，甾醇骨架的过氧化会导致其凝聚和有序性质部分降解，这与OOH取代的位置和异构体无关。然而，即使在所有磷脂和胆固醇都发生过氧化的大量过氧化膜中，甾醇骨架的凝聚和有序性质仍然很显著。讨论了其对膜侧向结构域形成的可能影响。还对胆固醇过氧自由基进行了研究，我们发现OO基团不会迁移至头基团区域。
