Patterns of cell death triggered in two different cell lines by HypF-N prefibrillar aggregates.
The finding that aggregates of disease-unrelated proteins can induce cell death indicates that proteins may act as potential toxins. Cells experiencing toxic protein aggregates often display modifications of the redox status and ion balance, eventually leading to apoptosis; however, in some cases, tissue and cultured cell types die with features of necrosis. To elucidate the pathways leading to such different outcomes, we studied the biochemical features of death in H-END and NIH/3T3 cells exposed to prefibrillar aggregates of a disease-unrelated protein. The two types of cells died by apoptosis and necrosis, respectively. The pattern of caspase and proapoptotic factor activation was investigated together with the extent of mitochondria impairment and the energy load in either cell line. Our data depict a scenario where the events related to the extrinsic pathway of apoptosis are the same in the two cell lines, the difference in the final outcome being related to the extent of mitochondria derangement, possibly due to the different ability of the cells to counteract ion homeostasis impairment.
Bucciantini
Monica
M
Department of Biochemical Sciences, University of Florence, Florence, Italy.
Rigacci
Stefania
S
Berti
Andrea
A
Pieri
Laura
L
Cecchi
Cristina
C
Nosi
Daniele
D
Formigli
Lucia
L
Chiti
Fabrizio
F
Stefani
Massimo
M
D000255:Adenosine Triphosphate / Q000032:analysis; D000682:Amyloid / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D001426:Bacterial Proteins; D019878:Carboxyl and Carbamoyl Transferases; D002352:Carrier Proteins / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D029968:Escherichia coli Proteins; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D041681:NIH 3T3 Cells; D009336:Necrosis; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D000682:Amyloid; D051023:BH3 Interacting Domain Death Agonist Protein; D001426:Bacterial Proteins; C494815:Bid protein, mouse; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C108878:HypF protein, Bacteria; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D000255:Adenosine Triphosphate; D019878:Carboxyl and Carbamoyl Transferases; C504838:hypF protein, E coli; D020169:Caspases