The effect of cholesterol and monosialoganglioside (GM1) on the release and aggregation of amyloid beta-peptide from liposomes prepared from brain membrane-like lipids.
In order to investigate the influence of cholesterol (Ch) and monosialoganglioside (GM1) on the release and subsequent deposition/aggregation of amyloid beta peptide (Abeta)-(1-40) and Abeta-(1-42), we have examined Abeta peptide model membrane interactions by circular dichroism, turbidity measurements, and transmission electron microscopy (TEM). Model liposomes containing Abeta peptide and a lipid mixture composition similar to that found in the cerebral cortex membranes (CCM-lipid) have been prepared. In all, four Abeta-containing liposomes were investigated: CCM-lipid; liposomes with no GM1 (GM1-free lipid); those with no cholesterol (Ch-free lipid); liposomes with neither cholesterol nor GM1 (Ch-GM1-free lipid). In CCM liposomes, Abeta was rapidly released from membranes to form a well defined fibril structure. However, for the GM1-free lipid, Abeta was first released to yield a fibril structure about the membrane surface, then the membrane became disrupted resulting in the formation of small vesicles. In Ch-free lipid, a fibril structure with a phospholipid membrane-like shadow formed, but this differed from the well defined fibril structure seen for CCM-lipid. In Ch-GM1-free lipid, no fibril structure formed, possibly because of membrane solubilization by Abeta. The absence of fibril structure was noted at physiological extracellular pH (7.4) and also at liposomal/endosomal pH (5.5). Our results suggest a possible role for both Ch and GM1 in the membrane release of Abeta from brain lipid bilayers.
Tashima
Yoshihiko
Y
Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka 814-0180, Japan.
Oe
Ryoko
R
Lee
Sannamu
S
Sugihara
Gohsuke
G
Chambers
Eric J
EJ
Takahashi
Mitsuo
M
Yamada
Tatsuo
T
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D002645:Chickens; D002784:Cholesterol / Q000378:metabolism / Q000502:physiology*; D002942:Circular Dichroism; D005677:G(M1) Ganglioside / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism*; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013997:Time Factors
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010446:Peptide Fragments; D010455:Peptides; C078592:amyloid beta-protein (1-40); D005677:G(M1) Ganglioside; D002784:Cholesterol