tailieunhanh - Báo cáo khoa học: Differing molecular mechanisms appear to underlie early toxicity of prefibrillar HypF-N aggregates to different cell types

Considerable attention has been paid to the high cytotoxic potential of small, prefibrillar aggregates of proteins⁄peptides, either associated or not associated with amyloid diseases. Recently, we reported that different cell types are variously affected by early aggregates of the N-terminal domain of the prokaryotic hydrogenase maturation factor HypF (HypF-N), a pro-tein not involved in any disease. | iFEBS Journal Differing molecular mechanisms appear to underlie early toxicity of prefibrillar HypF-N aggregates to different cell types f t ie ina í oc C h i1 Anns Ponealfini1 Qorona Ranlií-mi1 laiiHia Fii it illi i1 RoKor o f arii iralo2 Isiisuiiav ecciii Hl II la I cl Ioann II ucicna Day HUI II uiauuiarioiiiio nuuviiu Udpuidic Lucia Formigli3 Gianfranco Liguri1 4 and Massimo Stefani1 4 1 Department of BiochemicalSciences University of Florence Italy 2 . Hematology Azienda Ospedaliera Careggi Florence Italy 3 Department of Anatomy Histology and Forensic Medicine University of Florence Italy 4 Interuniversity Centre for the Study of the Molecular Basis of Neurodegenerative Diseases University of Florence Italy Keywords amyloid toxicity apoptosis mitochondrial permeability transition pore opening prefibrillar protein aggregates protein misfolding and cell death Correspondence C. Cecchi Department of Biochemical Sciences University of Florence viale Morgagni 50 50134 Florence Italy Fax 39 055 459 8905 Tel 39 055 459 8320 E-mail Received 10 February 2006 accepted 16 March 2006 doi Considerable attention has been paid to the high cytotoxic potential of small prefibrillar aggregates of proteins peptides either associated or not associated with amyloid diseases. Recently we reported that different cell types are variously affected by early aggregates of the N-terminal domain of the prokaryotic hydrogenase maturation factor HypF HypF-N a protein not involved in any disease. In this study we provide detailed information on a chain of events triggered in Hend murine endothelial cells and IMR90 fibroblasts which have previously been shown to be highly vulnerable or very resistant respectively to HypF-N aggregates. Initially both cell lines displayed impaired viability upon exposure to HypF-N toxic aggregates however at longer exposure times IMR90 cells recovered completely whereas Hend cells did not. In particular