Unsaturation in the Fatty Acids of Phospholipids Drastically Alters the Structure and Toxicity of Insulin Aggregates Grown in Their Presence

Overview

Journal J Phys Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2022 May 17

PMID 35580189

Authors

Mikhail Matveyenka

Stanislav Rizevsky

Dmitry Kurouski

Affiliations

Soon will be listed here.

Abstract

Lipid bilayers play an important role in the pathological assembly of amyloidogenic proteins and peptides. This assembly yields oligomers and fibrils, which are highly toxic protein aggregates. In this study, we investigated the role of saturation in fatty acids of two phospholipids that are present in cell membranes. We found that unsaturated cardiolipin (CL) drastically shortened the lag phase of insulin aggregation. Furthermore, structurally and morphologically different aggregates were formed in the presence of unsaturated CL vs saturated CL. These aggregates exerted drastically different cell toxicity. Both saturated and unsaturated phosphatidylcholine (PC) were able to inhibit insulin aggregation equally efficiently. Similar to CL, structurally different aggregates were formed in the presence of saturated and unsaturated PC. These aggregates exerted different cell toxicities. These results show that unsaturated phospholipids catalyze the formation of more toxic amyloid aggregates comparing to those formed in the presence of saturated lipids.

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