Curcumin Protects β-Lactoglobulin Fibril Formation and Fibril-Induced Neurotoxicity in PC12 Cells.

Mansooreh Mazaheri,Ali Akbar Moosavi-Movahedi,Fatemeh Shaerzadeh,Ali Akbar Saboury,Nader Sheibani,Fariba Khodagholi,Jamshidkhan Chamani

doi:10.1371/journal.pone.0133206

Mansooreh Mazaheri, Ali Akbar Moosavi-Movahedi + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0133206

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Abstract

In this study the β-lactoglobulin fibrillation, in the presence or absence of lead ions, aflatoxin M1 and curcumin, was evaluated using ThT fluorescence, Circular dichroism spectroscopy and atomic force microscopy. To investigate the toxicity of the different form of β-Lg fibrils, in the presence or absence of above toxins and curcumin, we monitored changes in the level of reactive oxygen species and morphology of the differentiated neuron-like PC12 cells. The cell viability, cell body area, average neurite length, neurite width, number of primary neurites, percent of bipolar cells and node/primary neurite ratios were used to assess the growth and complexity of PC12 cells exposed to different form of β-Lg fibrils. Incubation of β-Lg with curcumin resulted in a significant decrease in ROS levels even in the presence of lead ions and aflatoxin M1. The β-Lg fibrils formed in the presence of lead ions and aflatoxin M1 attenuated the growth and complexity of PC12 cells compared with other form of β-Lg fibrils. However, the adverse effects of these toxins and protein fibrils were negated in the presence of curcumin. Furthermore, the antioxidant and inhibitory effects of curcumin protected PC12 cells against fibril neurotoxicity and enhanced their survival. Thus, curcumin may provide a protective effect toward β-Lg, and perhaps other protein, fibrils mediated neurotoxicity.

Highlights

Amyloid fibrils are fibrillary protein aggregates that are implicated in a variety of human diseases [1,2,3,4]
We proposed that Aflatoxin M1 (AFM1) enters into the whey protein and interacts with the β-Lg affecting its fibrillation
It was shown that peptides, and not the intact monomers, are the building blocks of the fibrils derived from β-lg heated at 80°C and pH 2 [15]

Summary

Introduction

Amyloid fibrils are fibrillary protein aggregates that are implicated in a variety of human diseases [1,2,3,4]. Some researchers have shown that the amyloid fibril-forming propensity is a generic property of all polypeptides [5]. Certain metal ions contribute to pathogenesis of these degenerative diseases [6]. The generally accepted argument on the role of divalent metals in protein aggregation is based on their ability to act as bridges, as well as to provide an PLOS ONE | DOI:10.1371/journal.pone.0133206. Curcumin Protects β-Lactoglobulin Fibril Formation electrostatic screening between the negatively charged groups of the neighboring protein molecules [7]. Protein aggregation is generally promoted by the electrostatic screening due to the action of monovalent and/or divalent ions [8, 9]

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