U18666A Treatment Results in Cholesterol Accumulation, Reduced Na(+), K(+)-ATPase Activity, and Increased Oxidative Stress in Rat Cortical Astrocytes

Lipids
Daniela Copetti-SantosJanice Carneiro Coelho

Abstract

The objective of this study was to determine the effect of U18666A, an inhibitor of cholesterol synthesis and its intracellular transport, on oxidative stress parameters in cortical astrocytes cultured from Wistar rats (0-3 days old). The cultures were incubated with U18666A (0.25 µg/mL) for 48 h, conditions that are considered ideal to mimic Niemann-Pick type C disease. A variety of indicators of oxidative stress were measured. U18666A treatment increased cholesterol 2-fold in treated compared to control astrocytes. Oxidative stress was significantly elevated in treated cells as demonstrated by a 1.7-fold increase in thiobarbituric acid reactive substances, a 60% decrease is sulfhydral groups, and a 3.7-fold increase in carbonyl groups, indicative of increased lipid and protein oxidation following U18666A treatment. Consistent with these changes, both catalase and superoxide dismutase activities were significantly reduced nearly 50% in treated compared to control astrocytes. Collectively, these change resulted in a 50% reduction in Na(+), K(+)-ATPase specific activity following U18666A treatment, suggesting a significant alteration in its plasma membrane environment. Overall, these changes indicate that U18666A treatment resul...Continue Reading

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Aug 27, 2017·Orphanet Journal of Rare Diseases·Franziska PeterMoritz J Frech
Aug 18, 2018·Journal of Ophthalmology·Xinyue ShenHuaijin Guan
Apr 24, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Ana C CarreiraLiana C Silva

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