Comparison of the effects of aging in vivo and of oxygen free radicals in vitro on high-affinity choline uptake and hemicholinium-3 binding in the rat brain

Krištofíková, Zdena; Benešová, O; Tejkalová, H.

doi:10.1016/0167-4943(93)90049-n

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…Undepleted and cholesterol-depleted synaptosomes resuspended in Krebs-Ringer-HEPES-glucose buffer (128 mM NaCl, 5 mM KCl, 2.7 mM CaCl 2 , 1.2 mM MgSO 4 , 5 mM glucose and 10 mM HEPES, pH = 7.4) were preincubated with Ab 1-40 fragments and/or with enantiomers of 24-hydroxycholesterol for 15-60 min and subsequently with [3H]choline ([methyl-3H]choline chloride, PerkinElmer, specific activity 2,775.0 GBq/mmol) for 4 min, both at 37°C, in accordance with our previous study [33].…”

Section: Measurements Of High-affinity Choline Uptake (Hacu) Activitymentioning

confidence: 86%

Interactions of Amyloid β Peptide 1–40 and Cerebrosterol

et al. 2011

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Amyloid β peptides appear to play a role in physiological processes; however, they are also involved in the pathogenesis of Alzheimer disease. Their actions under normal conditions are probably mediated by soluble monomeric L-isoforms at low concentrations, perhaps via highly specific interactions. On the contrary, toxic effects of aggregated natural L-isoforms/synthetic D-isoforms on membranes are very similar, but synthetic reverse/random L: -isoforms without pronounced aggregation properties are not toxic. Our previous work reported interactions of non-aggregated/aggregated L-isoforms of amyloid β peptides 1-40/1-42 with racemic 24-hydroxycholesterol. In this study, stereospecificity in the interactions of natural 24(S)hydroxycholesterol (cerebrosterol) or synthetic 24(R)hydroxycholesterol with soluble fragment 1-40 was evaluated by means of an in vitro test based on increased vulnerability of the hemicholinium-3 sensitive high-affinity choline uptake system in rat hippocampal cholesterol-depleted synaptosomes to the actions of amyloid β; computational simulations were also performed. Our results suggest that: (1) 24(S)hydroxycholesterol interacts with L-peptide 1-40 but not with the reverse L-peptide 40-1, (2) 24(R)hydroxycholesterol does not interact with L-peptide 1-40 or reverse 40-1, and (3) both enantiomers can probably interact with D-peptide 1-40. Therefore, the binding of 24(S)hydroxycholesterol is not fully stereospecific and the interaction could not reflect a physiological mechanism. Data from the computational simulation indicate that the hydrophobic core of the amyloid β molecule interacts with the hydrophobic part of 24(S)hydroxycholesterol, but no hydrogen bonds with high stability were found. Using this procedure, globular amyloid β could retain 24(S)hydroxycholesterol and thus contribute to its pathological accumulation in the brains of patients with Alzheimer disease.

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Section: Measurements Of High-affinity Choline Uptake (Hacu) Activitymentioning

confidence: 86%

Interactions of Amyloid β Peptide 1–40 and Cerebrosterol

et al. 2011

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“…The result suggests the protective role of membrane cholesterol against toxic effects of 24-OH mediated probably through increased generation of reactive oxygen species [14]. It appears that depletionmediated changes in conformation of choline carriers could facilitate the direct interaction of oxysterol with membrane protein that is extremely sensitive to oxidative impairment [43].…”

Section: -Oh and Its Complex With Absmentioning

confidence: 98%

Complex of Amyloid β Peptides with 24-Hydroxycholesterol and Its Effect on Hemicholinium-3 Sensitive Carriers

et al. 2007

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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.

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“…on the lipid peroxide levels in animal models (Kristofiková et al 1995a, b), free radicals (Kristofiková et al 1993;Skoumalová et al 2003;Rofina et al 2004) and other possible mechanisms of ageing and dementia (Kristofiková et al 1998). Lately, they have focused on steroid metabolism of the brain (Kristofiková et al 2009;Rusina et al 2009), different metabolis markers and genetic aspects.…”

Section: Biogerontology In the Czech Republicmentioning

confidence: 96%

Biogerontology in the Czech Republic

Holmerová¹,

Vaňková²,

Jurašková

2010

Biogerontology

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Authors provide results of their review of research in the field of biogerontology. Despite the fact that the term "biogerontology" is not commonly used in Czech scientific practice, there have been many research efforts in this field. Up to present, the Czech research teams have focused on the theoretical and biological models of ageing, its immunological aspects, the risk factors of unsuccessfull human ageing, and also metabolic and nutritional factors. Many research teams are dealing with the mechanisms of the neurodegeneration. The authors conclude that better coordination and systematic funding of research in gerontology is needed because of the actual demographic challenges.

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Comparison of the effects of aging in vivo and of oxygen free radicals in vitro on high-affinity choline uptake and hemicholinium-3 binding in the rat brain

Cited by 10 publications

References 23 publications

Interactions of Amyloid β Peptide 1–40 and Cerebrosterol

Interactions of Amyloid β Peptide 1–40 and Cerebrosterol

Complex of Amyloid β Peptides with 24-Hydroxycholesterol and Its Effect on Hemicholinium-3 Sensitive Carriers

Biogerontology in the Czech Republic

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