Examining the levels of ganglioside and cholesterol in cell membrane on attenuation the cytotoxicity of beta-amyloid peptide
Resource
Colloids and Surfaces B: Biointerfaces 65 (2): 172-177
Journal
Colloids and Surfaces B: Biointerfaces
Journal Volume
65
Journal Issue
2
Pages
172-177
Date Issued
2008
Date
2008
Author(s)
Abstract
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.
SDGs
Other Subjects
Amines; Cholesterol; Cytotoxicity; Evaporative cooling systems; Glycoproteins; Membranes; Microfluidics; Photoacoustic effect; Plasma (human); Plasmas; Toxic materials; Alzheimer's disease (AD); amyloid peptides; Cholesterol levels; Concentration (composition); Elsevier (CO); In-cell; Lateral pressures; membrane surfaces; Plasma membrane (PM); Primary factors; Cell membranes; amyloid beta protein; amyloid beta protein[1-40]; amyloid beta protein[25-35]; cholesterol; ganglioside; ganglioside GM1; monomer; sialic acid; Alzheimer disease; amino acid sequence; animal cell; article; cell culture; cell membrane; cell strain; complex formation; concentration response; controlled study; cytotoxicity; inhibition kinetics; lipogenesis; molecular interaction; nonhuman; priority journal; protein conformation; protein protein interaction; Amyloid beta-Protein; Animals; Cell Membrane; Cholesterol; Circular Dichroism; G(M1) Ganglioside; PC12 Cells; Peptide Fragments; Rats
Type
journal article
File(s)![Thumbnail Image]()
Loading...
Name
20.pdf
Size
809.2 KB
Format
Adobe PDF
Checksum
(MD5):f0b52da52ebca88b441ff6f9be7542bf