Formation of Amyloid Fibers Triggered by Phosphatidylserine-Containing Membranes
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- 作者：Hongxia Zhao ; Esa K. J. Tuominen ; and Paavo K. J. Kinnunen
- 刊名：Biochemistry
- 出版年：2004
- 出版时间：August 17, 2004
- 年：2004
- 卷：43
- 期：32
- 页码：10302 - 10307
- 全文大小：350K
- 年卷期：v.43,no.32(August 17, 2004)
- ISSN：1520-4995
文摘
Protein misfolding has been shown to be the direct cause of a number of highly devastatingdiseases such as Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob syndrome, affecting theaging population globally. The deposition in tissues of amyloid fibrils is a characteristic of all these diseases,and the mechanisms by which these protein aggregates form continue to be intensively investigated. Inonly a fraction of cases is an underlying mutation responsible, and accordingly, what initiates amyloidformation in vivo is the major question that is addressed. In this study, we show that membranes containingphosphatidylserine (PS), a negatively charged phospholipid, induce a rapid formation of fibers by a varietyof proteins, viz., lysozyme, insulin, glyceraldehyde-3-phosphate dehydrogenase, myoglobin, transthyretin,cytochrome c, histone H1, and 
-lactalbumin. Congo red staining of these fibers yields the characteristiclight green birefringence of amyloid, and fluorescent lipid tracers further reveal them to includephospholipids. Our results suggest that PS as well as other acidic phospholipids could provide thephysiological low-pH environment on cellular membranes, enhancing protein fibril formation in vivo.Interestingly, all the proteins mentioned above either are cytotoxic or induce apoptosis. PS-proteininteraction could be involved in the mechanism of cytotoxicity of the aggregated protein fibrils, perturbingmembrane functions. Importantly, our results suggest that this process induced by acidic phospholipidsmay provide an unprecedented and generic connection between three current major areas of research: (i)mechanism(s) triggering amyloid formation, (ii) cytotoxicity of amyloidal protein aggregates, and (iii)mechanism(s) of action of cytotoxic proteins.
-lactalbumin. Congo red staining of these fibers yields the characteristiclight green birefringence of amyloid, and fluorescent lipid tracers further reveal them to includephospholipids. Our results suggest that PS as well as other acidic phospholipids could provide thephysiological low-pH environment on cellular membranes, enhancing protein fibril formation in vivo.Interestingly, all the proteins mentioned above either are cytotoxic or induce apoptosis. PS-proteininteraction could be involved in the mechanism of cytotoxicity of the aggregated protein fibrils, perturbingmembrane functions. Importantly, our results suggest that this process induced by acidic phospholipidsmay provide an unprecedented and generic connection between three current major areas of research: (i)mechanism(s) triggering amyloid formation, (ii) cytotoxicity of amyloidal protein aggregates, and (iii)mechanism(s) of action of cytotoxic proteins.