Examining the levels of ganglioside and cholesterol in cell membrane on attenuation the cytotoxicity of beta-amyloid peptide.
The deposition of beta-amyloid (Abeta) on cell membranes is considered as one of the primary factors in having Alzheimer's disease (AD). Recent studies have suggested that certain components of plasma membrane, ganglioside and cholesterol could accelerate the accumulation of Abeta on the plasma membranes. However, the effect of cholesterol and ganglioside (GM1) on Abeta cytotoxicity is still a controversial issue. The aim of this study is to understand the roles of GM1 and cholesterol in AD by using PC12, a neuron-like cell. The effects of the sequence, conformation, and concentration of Abeta on cytotoxicity were also investigated. Monomeric Abeta could attack the plasma membrane resulting in cytotoxicity, however, fibrillar Abeta was found to be less toxic. Our results showed that Abeta (1-40) was more toxic than Abeta (25-35) and the cytotoxicity of Abeta was proportional to its concentration. Besides, the depletion of GM1 from plasma membrane, it would block the Abeta-induced cytotoxicity. Decreasing the cholesterol level by around 30% could attenuate the cytotoxicity of Abeta. These findings validate our idea that the cholesterol could stabilize the lateral pressure derived from the formation of GM1-Abeta complex on the membrane surface. Furthermore, both GM1 and cholesterol are essential in mechanism of Abeta accumulation and could modulate the cytotoxicity of monomeric Abeta.
Lin
Ming-Shen
MS
Department of Chemical and Materials Engineering, National Central University, Jhong-Li 320, Taiwan.
Chen
Liang-Yu
LY
Wang
Steven S S
SS
Chang
Yung
Y
Chen
Wen-Yih
WY
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002942:Circular Dichroism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D005677:G(M1) Ganglioside; D002784:Cholesterol