Phosphatidylethanolamine plasmalogen enhances the inhibiting effect of phosphatidylethanolamine on γ-secretase activity
Phosphatidylethanolamine plasmalogen enhances the inhibiting effect of phosphatidylethanolamine on γ-secretase activity
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DOI：
10.1093/jb/mvu074
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发表时间：
2015-05-01
影响因子：
2.7
通讯作者：
Kaneko, Jun
中科院分区：
文献类型：
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作者：
Onodera, Tomoko;Futai, Eugene;Kaneko, Jun
缩醛磷脂广泛存在于动物和某些厌氧菌的生物膜中，但其在细胞膜中的功能尚不清楚。阿尔茨海默病患者脑组织中磷脂酰乙醇胺血浆酶原（PEPls）的减少促使我们研究膜磷脂质组成对产生淀粉样β蛋白（A β）的γ-分泌酶活性的影响。为了阐明磷脂（包括PEP I）对A β产生的影响，在体外测定中使用酵母微粒体和重构脂质体测量γ-分泌酶活性。蛋白脂质体中乙醇胺磷脂的存在减弱了γ-分泌酶的活性。此外，总乙醇胺磷脂中增加的PEP 1 s含量进一步降低了酶活性，表明γ-分泌酶活性受膜磷脂PEP 1 s/PE比率的影响。此外，来自厌氧细菌细胞膜的PEPls诱导γ-分泌酶活性的相同效果。
Plasmalogens (Pls) are widely distributed in the biological membrane of animals and certain anaerobic bacteria, but their functions in the cell membrane are still poorly understood. Decrease of phosphatidylethanolamine plasmalogen (PEPls) in the brain tissue of patients with Alzheimer's disease prompted us to investigate the effect of the membrane phosphorus lipid composition on the activity of gamma-secretase that produces amyloid-beta protein (A beta). To clarify the effect of phospholipids, including PEPls, on A beta production, gamma-secretase activity was measured in an in vitro assay using yeast microsomes and reconstituted liposomes. The presence of ethanolamine phospholipids in the proteoliposome weakened gamma-secretase activity. In addition, increased PEPls content in total ethanolamine phospholipids further decreased the enzyme activity, indicating that gamma-secretase activity is affected by the membrane phospholipid PEPls/PE ratio. Furthermore, PEPls from anaerobic bacterial cell membrane induced the same effect on gamma-secretase activity.