Mechanism of rutin mediated inhibition of insulin amyloid formation and protection of Neuro‑2a cells from fbril‑induced apoptosis.

Mahendra, V. P. and Yogendra Prasad, K. and Ganesan, P. and Ravi, Kumar (2020) Mechanism of rutin mediated inhibition of insulin amyloid formation and protection of Neuro‑2a cells from fbril‑induced apoptosis. Molecular Biology Reports, 47. pp. 2811-2820. ISSN 0301-4851

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Abstract

Many metabolic and neurodegenerative diseases are associated with protein misfolding and aggregation. Insulin a key hormone, under certain conditions aggregates and forms pathological amyloid fbrils. Several polyphenols have been studied extensively to elucidate their inhibitory efect on amyloid formation. In the present study, we used insulin as an amyloid model to test the mechanism and efcacy of rutin as an anti-amyloidogenic molecule. By using electron microscopy, dynamic light scattering and circular dichroism spectroscopy, we show that rutin inhibits the insulin aggregate and fbril formation. Further, rutin interacts with insulin directly and inhibits fbril formation in a dose-dependent manner as demonstrated by micro scale thermophoresis experiments. The molecular docking study predicted the potential binding pocket of rutin at the interface of chain A and chain B of insulin thereby preventing it from forming the aggregates. Since, rutin is a natural anti-oxidant, we studied its role in diminishing amyloid fbril induced cytotoxicity and apoptosis. Rutin, decreases the insulin amyloid fbrils-induced Neuro-2a cytotoxicity by reducing reactive oxygen species (ROS) levels which in turn downregulates Bax and upregulates Bcl-2 and pBad proteins. These fndings suggest the potential action of rutin in preventing protein misfolding, cell death, and serves as a lead structure to design novel anti-amyloidosis compounds.

Item Type:	Article
Uncontrolled Keywords:	Rutin · Fibrils · Cytotoxicity
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 13 Molecular Biochemistry 600 Technology > 01 Medical sciences > 04 Diabetes Mellitus
Divisions:	Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	03 Dec 2020 04:28
Last Modified:	03 Dec 2020 04:28
URI:	http://ir.cftri.res.in/id/eprint/14678

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