Beta-amyloid peptide (AbP1-40) forms a pathway for ion flux across neuronal membranes. When incorporated into a bilayer, AbP forms cation selective channels (Arispe N. et al., 1992, Proc.Natl. Acad. Sci., 90:567-571.). Recent studies have suggested the importance of cholesterol in AbP aggregation and binding to membranes (Wang S. et al., 2001, J.Biol.Chem., 276:42027-42034). In this study, we used a voltage-clamp technique (Stipani V. et al., 2001, Biophys. J., 81:3332-3338) and obtained the same results of Arispe N. et al. in phosphatidylserine:phosphatidylethanolamine (50:50, w:w) membranes; then we extended the investigation to the interaction of AbP with artificial lipid membranes made of oxidized cholesterol. In these membranes, AbP (AbP concentration of 5*10-8 M; 50 mM KCl; ph=7; T=22 +/-2 °C) was able to form channels with different conductance levels, life times and occurrence frequenties. It is worth recalling that oxidized cholesterol membranes contain cholesterol and other products characteristic of aged cholestherol such as 7-dihydrocholesterol wich could enable them to simulate physiologically-aged membranes. These results indicate the importance of cholesterol domains in the incorporation and assemly of AbP in the membrane.
Channel formation by b-amyloid peptide AbP(1-40) in black lipid membranes made of oxidized cholesterol
MELELEO D.;
2003-01-01
Abstract
Beta-amyloid peptide (AbP1-40) forms a pathway for ion flux across neuronal membranes. When incorporated into a bilayer, AbP forms cation selective channels (Arispe N. et al., 1992, Proc.Natl. Acad. Sci., 90:567-571.). Recent studies have suggested the importance of cholesterol in AbP aggregation and binding to membranes (Wang S. et al., 2001, J.Biol.Chem., 276:42027-42034). In this study, we used a voltage-clamp technique (Stipani V. et al., 2001, Biophys. J., 81:3332-3338) and obtained the same results of Arispe N. et al. in phosphatidylserine:phosphatidylethanolamine (50:50, w:w) membranes; then we extended the investigation to the interaction of AbP with artificial lipid membranes made of oxidized cholesterol. In these membranes, AbP (AbP concentration of 5*10-8 M; 50 mM KCl; ph=7; T=22 +/-2 °C) was able to form channels with different conductance levels, life times and occurrence frequenties. It is worth recalling that oxidized cholesterol membranes contain cholesterol and other products characteristic of aged cholestherol such as 7-dihydrocholesterol wich could enable them to simulate physiologically-aged membranes. These results indicate the importance of cholesterol domains in the incorporation and assemly of AbP in the membrane.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
