Primary Aminophospholipids in the External Layer of Liposomes Protect Their Component Polyunsaturated Fatty Acids from 2,2‘-Azobis(2-amidinopropane)- dihydrochloride-Mediated Lipid Peroxidation

We showed in our previous study that docosahexaenoic acid-rich phosphatidylethanolamine in the external layer of small-size liposomes, as a model for biomembranes, protected its docosahexaenoic acid from 2,2'-azobis(2-amidinopropane)dihydrochloride- (AAPH-) mediated lipid peroxidation in vitro. Besides phosphatidylethanolamine, both phosphatidylserine and an alkenyl-acyl analogue of phosphatidylethanolamine, phosphatidylethanolamine plasmalogen, are reported to possess characteristic antioxidant activities. However, there are few reports about the relationship between the protective activity of phosphatidylethanolamine plasmalogen and/or phosphatidylserine against lipid peroxidation and their distribution in a phospholipid bilayer. Furthermore, it is unclear whether phosphatidylethanolamine plasmalogen and/or phosphatidylserine protect their component polyunsaturated fatty acids (PUFAs) from lipid peroxidation. In the present study, we examined the relationship between the transbilayer distribution of aminophospholipids, such as phosphatidylethanolamine rich in arachidonic acid, phosphatidylethanolamine plasmalogen, and phosphatidylserine, and the oxidative stability of their component PUFAs. The transbilayer distribution of these aminophospholipids in liposomes was modulated by coexisting phosphatidylcholine bearing two types of acyl chain: dipalmitoyl or dioleoyl. The amounts of these primary aminophospholipids in the external layer became significantly higher in liposomes containing dioleoylphosphatidylcholine than in those containing dipalmitoylphosphatidylcholine. Phosphatidylethanolamine rich in arachidonic acid, phosphatidylethanolamine plasmalogen or phosphatidylserine in the external layer of liposomes, as well as external docosahexaenoic acid-rich phosphatidylethanolamine, were able to protect their component PUFAs from AAPH-mediated lipid peroxidation.