Effect of EGCG On Fe(III)‐induced conformational transition of silk fibroin, a model of protein related to neurodegenerative diseases

Abstract

The abnormal aggregation of amyloid proteins is reported to play a critical role in the etiology of neurodegenerative disorders. Studies have shown that excessive ferric irons are associated with the misfolding of amyloid proteins, and that (-)-epigallocatechin gallate (EGCG) is a good metallic ion chelator with inhibitory effect on the aggregation of amyloid proteins. EGCG has been thus considered as a potential drug candidate for the treatment of neurodegenerative diseases. However, the mechanism of action for EGCG in inhibition of aggregation of amyloid proteins is still remaining unclear. Silk fibroin (SF) shares similarities with amyloid proteins in some amino acid sequences and fibrillation kinetics. In this work, therefore, we used SF as a model of protein to investigate the effects of Fe(III) and EGCG on conformational transition by using turbidity assay, thioflavin T (ThT) fluorescence spectroscopy, Raman spectroscopy, and atomic force microscope (AFM). We demonstrated that low concentration of Fe(III) ions promoted the formation of β-sheet conformers, while high concentration of Fe(III) ions inhibited further aggregation of SF. EGCG could significantly inhibit the conformational transition of SF when induced by Fe(III), and decrease the amount of β-sheet conformers dose-dependently. The findings provide important information regarding to EGCG as a potential agent for the prevention and treatment of neurodegenerative diseases. Fe(III) can accelerate the conformation transition of silk fibrion (SF) from random coil into β-sheet, while (-)-epigallocatechin gallate (EGCG) inhibits Fe(III)-induced β-sheet aggregation of SF., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 100-107, 2016.

Disruption of the Metal Ion Environment by EDTA for Silk Formation Affects the Mechanical Properties of Silkworm Silk

“…However, K + and Na + can break down the silk fibroin network in vitro [15,38]. On the other hand, copper, iron, zinc, and magnesium ions can increase the β-sheet structure of silk fibroin in vitro [14,15,39,40]. Furthermore, injection of FeCl 3 can increase their strength and toughness [16,36,39].…”

“…On the other hand, copper, iron, zinc, and magnesium ions can increase the β-sheet structure of silk fibroin in vitro [14,15,39,40]. Furthermore, injection of FeCl 3 can increase their strength and toughness [16,36,39]. Injection of CuCl 2 can increase the strength of silk fiber [17].…”

Complex of EGCG with Cu(II) Suppresses Amyloid Aggregation and Cu(II)-Induced Cytotoxicity of α-Synuclein

“…There is extensive epidemiological evidence for green tea health benefits. EGCG extracted from green tea can chelate metal ions to form the complex which can be used for the treatment of neurodegenerative disorders [36,37]. EGCG interacts with α-Syn competitively when Cu(II) is present, resulting in the inhibition of α-Syn fibrillation induced by Cu(II).…”

Silk Fibroin Hydrogels Could Be Therapeutic Biomaterials for Neurological Diseases

“…The highly repetitive GAGAGS in SF can be analogous in structure to VGGVV in amyloidosis β 42 peptide and VGGAVVAGV in alpha-synuclein [ 89 ]. Simultaneously, the silk I structure (random coil and helix-like forms) turns into silk II (beta-sheet and beta-sheet-like forms), a nucleation-dependent conformation transition principle, that bears extreme resemblance to that of neurodegenerative-related proteins [ 90 ]. The antioxidant, neuroprotective, and acetylcholinesterase inhibitory mechanisms of silk proteins could prove promising in the treatment of neurodegenerative diseases [ 91 ].…”