Unsaturation in the Fatty Acids of Phospholipids Drastically Alters the Structure and Toxicity of Insulin Aggregates Grown in Their Presence
JOURNAL OF PHYSICAL CHEMISTRY LETTERS(2022)
Abstract
Lipid bilayers play an important role in the pathological assembly of amyloidogenic proteins and peptides. This assembly yields oligomers andfibrils, which are highly toxic protein aggregates. In this study, we investigated therole of saturation in fatty acids of two phospholipids that are present in cellmembranes. We found that unsaturated cardiolipin (CL) drastically shortened thelag phase of insulin aggregation. Furthermore, structurally and morphologicallydifferent aggregates were formed in the presence of unsaturated CL vs saturatedCL. These aggregates exerted drastically different cell toxicity. Both saturated andunsaturated phosphatidylcholine (PC) were able to inhibit insulin aggregationequally efficiently. Similar to CL, structurally different aggregates were formed inthe presence of saturated and unsaturated PC. These aggregates exerted differentcell toxicities. These results show that unsaturated phospholipids catalyze theformation of more toxic amyloid aggregates comparing to those formed in the presence of saturated lipids
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Key words
phospholipids drastically,insulin aggregates,fatty acids
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