title: Prefibrillar aggregates of yeast prion Sup35NM and its variant are toxic to mammalian cells.
abstract: The deposition of proteins as insoluble amyloid aggregates is a characteristic feature of more than 20 degenerative conditions. A growing body of evidence indicates that the oligomeric species formed by proteins, but not the mature fibrils, are inherently toxic and are associated with clinical diseases. The N-terminal and middle region of Sup35 (Sup35NM), a yeast prion, can assemble into oligomers and fibrils. Here we analyze the cytotoxicity of different aggregates of Sup35NM and its variant, the proteins that is not associated with clinical disease. Our results showed that prefibrillar aggregates generated from Sup35NM and its variant Sup35NM-1 were toxic to cultured mammalian cells. In addition, the activation of caspase-3, 8, and 9 were detected, suggesting that apoptosis was involved in the observed cytotoxicity. Our findings provide evidence for the underlying mechanism of amyloid aggregate-induced cytotoxicity and suggest that it may arise from common structural features of the aggregates rather than from primary amino acid sequences.
authors: State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, #9, Dong Dan San Tiao, Dong Cheng District, Beijing 100730, People's Republic of China.
authors: Yingxia
authors: Y
authors: Liu
authors: Haiyan
authors: H
authors: Wei
authors: Jianguo
authors: J
authors: Qu
authors: Jianwei
authors: J
authors: Wang
authors: Tao
authors: T
authors: Hung
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D052160:Benzothiazoles; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D046529:Microscopy, Electron, Transmission; D010454:Peptide Termination Factors / Q000378:metabolism / Q000633:toxicity*; D011419:Propidium; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity* / Q000648:ultrastructure; D013844:Thiazoles / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism
chemical_list: D017304:Annexin A5; D052160:Benzothiazoles; D010454:Peptide Termination Factors; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013844:Thiazoles; C009462:thioflavin T; D011419:Propidium; D020169:Caspases