Aggregation and Cellular Toxicity of Pathogenic or Non-pathogenic Proteins

Sungmun Lee, Myung Chul Choi, Kenana Al Adem, Suryani Lukman, Tae Yeon Kim

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

More than 20 unique diseases such as diabetes, Alzheimer’s disease, Parkinson’s disease are caused by the abnormal aggregations of pathogenic proteins such as amylin, β-amyloid (Aβ), and α-synuclein. All pathogenic proteins differ from each other in biological function, primary sequences, and morphologies; however, the proteins are toxic when aggregated. Here, we investigated the cellular toxicity of pathogenic or non-pathogenic protein aggregates. In this study, six proteins were selected and they were incubated at acid pH and high temperature. The aggregation kinetic and cellular toxicity of protein species with time were characterized. Three non-pathogenic proteins, bovine serum albumin (BSA), catalase, and pepsin at pH 2 and 65 °C were stable in protein structure and non-toxic at a lower concentration of 1 mg/mL. They formed aggregates at a higher concentration of 20 mg/mL with time and they induced the toxicity in short incubation time points, 10 min and 20 min only and they became non-toxic after 30 min. Other three pathogenic proteins, lysozyme, superoxide dismutase (SOD), and insulin, also produced the aggregates with time and they caused cytotoxicity at both 1 mg/mL and 20 mg/mL after 10 min. TEM images and DSC analysis demonstrated that fibrils or aggregates at 1 mg/mL induced cellular toxicity due to low thermal stability. In DSC data, fibrils or aggregates of pathogenic proteins had low thermal transition compared to fresh samples. The results provide useful information to understand the aggregation and cellular toxicity of pathogenic and non-pathogenic proteins.

Original languageBritish English
Article number5120
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020

Fingerprint

Dive into the research topics of 'Aggregation and Cellular Toxicity of Pathogenic or Non-pathogenic Proteins'. Together they form a unique fingerprint.

Cite this