Complex of amyloid beta peptides with 24-hydroxycholesterol and its effect on hemicholinium-3 sensitive carriers.
Brains of Alzheimer disease patients in early stages of dementia contain an increased 24(S)-hydroxycholesterol (cerebrosterol)/cholesterol ratio when compared to controls. In this study, effects of amyloid beta peptides and of racemic 24-hydroxycholesterol were evaluated in vitro on undepleted or cholesterol-depleted hippocampal synaptosomes of young and old rats via a high-affinity choline transport and membrane anisotropy measurements. Depletion of membrane cholesterol decreased the transport of [3H]choline, increased the specific binding of [3H]hemicholinium-3 and decreased membrane anisotropy. However, less alterations were found in old when compared to young brains. 500 nM nonaggregated peptides were ineffective but aggregated fragment 1-42 evoked marked drops in the transport and anisotropy values on depleted synaptosomes. 50 microM 24-hydroxycholesterol inhibited choline transport on depleted synaptosomes but it did not influence membrane anisotropy. Peptides eliminated the actions of oxysterol on choline carriers in young but not in old rats. On the other hand, oxysterol eliminated the effects of peptides on membrane anisotropy. Our study suggests a possible role of membrane cholesterol in the regulation of choline carriers and supports data reporting a protective role of membrane cholesterol against toxic effects of amyloid beta peptides. Moreover, via Raman spectroscopy we demonstrate for the first time that peptides form a complex with 24-hydroxycholesterol.
Kristofiková
Zdena
Z
Alzheimer Disease Centre, Prague Psychiatric Centre, Ustavní 91, Prague 8 - Bohnice 181 03, Czech Republic. kristofikova@pcp.lf3.cuni.cz
Kopecký
Vladimír
V
Hofbauerová
Katerina
K
Hovorková
Petra
P
Rípová
Daniela
D
D000375:Aging / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D016880:Anisotropy; D018678:Cholinergic Agents / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004161:Diphenylhexatriene; D005456:Fluorescent Dyes; D006426:Hemicholinium 3 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006888:Hydroxycholesterols / Q000737:chemistry* / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000378:metabolism; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D050479:Neurotransmitter Transport Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013059:Spectrum Analysis, Raman; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018678:Cholinergic Agents; D005456:Fluorescent Dyes; D006888:Hydroxycholesterols; D026901:Membrane Transport Proteins; D050479:Neurotransmitter Transport Proteins; C065637:choline transporter; D004161:Diphenylhexatriene; D006426:Hemicholinium 3; C044563:24-hydroxycholesterol
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