Amyloid fibrillation and cytotoxicity of insulin are inhibited by the amphiphilic surfactants

Abstract

Amyloid fibrils have been associated with at least 25 different degenerative diseases. The 51-residue polypeptide hormone insulin, which is associated with type II diabetes, has been shown to self-assemble to form amyloid fibrils in vitro. With bovine insulin as a model, the research presented here explores the effects of two amphiphilic surfactants (1,2-dihexanoyl-sn-glycero-3-phosphocholine (di-C7-PC) and 1,2-diheptanoyl-sn-glycero-3-phosphocholine (di-C7-PC)) on the in vitro fibrillation process of bovine insulin at pH 2.0 and 55 degrees C. We demonstrated that insulin fibrillation may be inhibited by both surfactants in a dose-dependent fashion. The best inhibition of fibril formation is observed when insulin is incubated with 4mM di-C7-PC. Moreover, the addition of either surfactant at the concentrations studied attenuated insulin fibril-induced cytotoxicity in both PC12 and SH-SY5Y cell lines. The results from this work may contribute to the understanding of the molecular factors affecting amyloid fibrillation and the molecular mechanism(s) of the interactions between the membrane and amyloid proteins.

DHPC Strongly Affects the Structure and Oligomerization Propensity of Alzheimer's Aβ(1–40) Peptide

“…77 In addition, it was found that submicellar DHPC concentrations (below 8 mM) decelerate insulin aggregation, while at the same concentrations, no conformational transitions of the protein solution structure could be detected by CD. 78 Our current textbook view on lipids in living organisms is dominated by the concept of intact lipid bilayers, which enclose the cells as plasma membranes or define certain intracellular compartments, such as Golgi apparatus, endoplasmic reticulum and a plethora of different vesicular structures. However, it is important to note that lipids may naturally occur also outside these well-defined lipid compartments, although there is little information about the extent to which this happens.…”

In Silicoandin VitroStudy of Binding Affinity of Tripeptides to Amyloid β Fibrils: Implications for Alzheimer’s Disease

“…19 At present, no medication is available for AD, but there are evidences suggesting that reduction of amyloid assemblies can be favorable for animals and cells models of amyloidosis. 15,[20][21][22] Morgan et al have shown that laminin-1 can cause complete disassembly of fibrils into protofilaments and amorphous aggregates. 23 Fibril disaggregation induced by laminin-1 also contributed to the prevention of amyloid toxicity on hippocampal neuronal cells.…”

Modeling of chemical inhibition from amyloid protein aggregation kinetics

“…The kinetics of insulin inhibition induced by (−)-epigallocatechin-3-gallate (EGCG) were selected from Wang et al [31], methylglyoxal effects were collected from Oliveira et al [32] and those produced by 1,2-diheptanoyl-sn-glycero-3-phosphocholine (di-C7-PC) were described in Wang et al [33]. Two conditions of EGCG affecting to fibrillation kinetics were used: EGCG_1 (case 1) studied at pH = 2.0/T = 60°C and EGCG_2 (case 2) at pH = 7.4/T = 37°C.…”

“…The meanings of other symbolic notations as well as the corresponding units are summarized in Table 1. In the experimental data chosen, the dependent variable of response or time-dependent signals ( X ) to detect amyloid protein aggregation were absorbance at 600 nm (data obtained from Wang et al [31]), relative ThT fluorescence intensity (%) (data from Wang et al [33]) and ThT fluorescence intensity at 482 nm or 490 nm (data obtained from Thapa et al [16]; Kanapathipillaia et al [15]; Oliveira et al [32] and Vilasi et al [34]).…”