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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: There is evidence that dietary lipids and age both influence neuronal membrane composition and receptor G protein-linked signal transduction, but very little information is available on the interaction between these two factors. To investigate this, we obtained striata from 2, 12, and 22-month-old male F344 rats who were fed either a high-cholesterol, high-saturated fat or low-fat diet for 1 month. The striata were assayed for muscarinic agonist-stimulated low-Km GTPase activity using 10−3M carbachol and 10−5M oxotremorine and for KCl-evoked dopamine release enhancement by 10−5M oxotremorine. Membrane cholesterol and phospholipid content and phospholipid class composition were also determined. Mature animals showed significant but divergent changes in GTPase activity and dopamine release for high-cholesterol and low-fat diets: GTPase activity decreased, whereas dopamine release increased in these groups. Alterations in GTPase activity but not in dopamine release were inversely correlated with the cholesterol/phospholipid molar ratio. Old control animals showed reductions in both GTPase activity and oxotremorine-enhanced dopamine release compared with young animals. Whereas none of the experimental diets affected GTPase activity in old animals, the low-fat diet produced a marked decrease in dopamine release. In contrast to mature and old groups, young rats showed no significant change in either GTPase or dopamine release, suggesting a relative “resistance” to such dietary lipid modulation. The observed dissociation in GTPase and dopamine release responses to diet may reflect differing effects of these diets on discrete membrane lipid domains that preferentially influence different signal transduction components. The substantial age-related differences in striatal membrane response to dietary lipid modulation may represent the effects of underlying age differences in membrane lipid metabolism, structure, and/or dynamics. Our findings support the work of other groups that have shown that brain membranes are susceptible to modification by exogenous lipids. They also suggest the need for a more systematic examination of the influence of age on the response to other types of dietary lipid changes.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 69 (1997), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In a model recently developed to study the parameters altering vulnerability to oxidative stress, it was shown via image analysis that H2O2-exposed PC12 cells exhibited increased levels of intracellular Ca2+ (baseline), decreases in K+-stimulated Ca2+ levels (peak), and decreased poststimulation Ca2+ clearance (recovery). The present experiments were performed to determine if the response patterns in these parameters to oxidative stress would be altered after modification of membrane lipid composition induced by incubating the PC12 cells with 660 µM cholesterol (CHL) in the presence or absence of 500 µM sphingomyelin (SPH) before low (5 µM) or high (300 µM) H2O2 exposure. Neither CHL nor SPH had synergistic effects with high concentrations of H2O2 on baseline. However, CHL in the presence or absence of SPH reversed the effect of low concentrations of H2O2 on baseline. SPH decreased significantly the cell's ability to clear excess Ca2+ in the presence or absence of H2O2 and increased significantly the level of conjugated dienes (CDs). It is surprising that in the cells pretreated with CHL, the CD levels were not significantly different from controls. However, in the presence of SPH, the effects of CHL on CDs were altered. These results suggest that the ratios of membrane lipids could be of critical importance in determining the vulnerability to oxidative stress and Ca2+ translocation in membranes. This may be of critical importance in aging where there is increased membrane SPH and significant loss of calcium homeostasis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-4919
    Keywords: aging ; parotid cells ; alpha1-adrenergic ; s-adenosylmethionine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The age related decrease in alpha1-adrenergic stimulated inositol 1,4,5 trisphosphate (IP3) production in parotid cells of aged rats can be partially restored by treatment with S-adenosylmethionine (SAM). This effect is completely blocked by S-adenosyl homocysteine (SAH) and occurs in association with an increase in the conversion of phosphatidylethanolamine to phosphatidylcholine and a decrease in membrane viscosity. In contrast, SAM treatment actually inhibits stimulated IP3 production in cells of young rats. The membrane viscosity of these cells is lower than that of those from aged rats. Although conversion of phosphatidylethanolamine to phosphatidylcholine is enhanced, no further decrease in membrane viscosity is elicited in young cell preparations. These findings suggest that age changes in the membrane environment may result in impaired alpha1-adrenergic signal transduction and that such alterations may be at least partially reversible by SAM treatment.
    Type of Medium: Electronic Resource
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