caa a22 4500 445355824 CHVBK 20180317142859.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10072-011-0811-1 doi (NATIONALLICENCE)springer-10.1007/s10072-011-0811-1 Prefibrillar aggregates of yeast prion Sup35NM and its variant are toxic to mammalian cells [Elektronische Daten] [Yingxia Liu, Haiyan Wei, Jianguo Qu, Jianwei Wang, Tao Hung] 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. Springer-Verlag, 2011 Sup35NM nationallicence Yeast prion nationallicence Aggregation nationallicence Cytotoxicity nationallicence Apoptosis nationallicence PrD : Prion domain nationallicence TSE : Transmission spongiform encephalopathy nationallicence TEM : Transmission electron microscopy nationallicence PBS : 10mM sodium phosphate, 1.8mM potassium phosphate, 140mM NaCl, and 2.7mM potassium chloride, pH 7.4 nationallicence ThT : Thioflavin T nationallicence PI : Propidium iodide nationallicence Liu Yingxia 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, 100730, Beijing, People's Republic of China aut Wei Haiyan 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, 100730, Beijing, People's Republic of China aut Qu Jianguo National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 100052, Beijing, People's Republic of China aut Wang Jianwei 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, 100730, Beijing, People's Republic of China aut Hung Tao National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 100052, Beijing, People's Republic of China aut Neurological Sciences Springer Milan 32/6(2011-12-01), 1147-1152 1590-1874 32:6<1147 2011 32 10072 https://doi.org/10.1007/s10072-011-0811-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10072-011-0811-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Yingxia 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, 100730, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wei Haiyan 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, 100730, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Qu Jianguo National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 100052, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wang Jianwei 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, 100730, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Hung Tao National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 100052, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- Neurological Sciences Springer Milan 32/6(2011-12-01), 1147-1152 1590-1874 32:6<1147 2011 32 10072 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer