Peroxisome proliferator-activated receptor agonists prevent 25-OH-cholesterol induced c-jun activation and cell deathReportar como inadecuado

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BMC Pharmacology

, 1:10

First Online: 27 November 2001Received: 27 October 2001Accepted: 27 November 2001


BackgroundCholesterol oxides, the oxygenated derivatives of cholesterol, have been shown to cause programmed cell death in a variety of cell types. Using N9 microglia, this study was designed to investigate the molecular events induced by cholesterol oxides prior to the execution of programmed cell death.

ResultsMicroglia were very sensitive to 25-OH-cholesterol, such that a 2-day treatment of the cells with 5 μM 25-OH-cholesterol reduced cell viability to 5–10% of controls. There was a dose- and time-dependent increase in c-jun and phospho-c-jun levels in microglia prior to this 25-OH-cholesterol induced cell death. In contrast, 7-β-OH-cholesterol, which was relatively non-toxic to microglia, did not increase phospho-c-jun levels. Peroxisome proliferator-activated receptors PPARs are a group of nuclear receptors that have important roles in atherogenesis. Results from this study indicate that PPAR agonists such as 15d-PGJ2, indomethacin and WY14643 can attenuate cholesterol oxide induced c-jun activation and cell death in microglia.

ConclusionsPeroxisome proliferator-activated receptor agonists may be useful in future development of pharmacological agents against cholesterol oxide induced cytotoxicity.

List of abbreviations15d-PGJ215-deoxy-delta 12, 14-PGJ2

AP-1activator protein-1

ERKp42-44, Extracellular signal-Regulated Kinase

LDLlow density lipoprotein

MAP kinasesMitogen-Activated Protein kinases

MTT 3-45-dimethylthiazole-2yl-2,5-diphenyltetrazolium bromide

PCDprogrammed cell death

PPARsperoxisome proliferator-activated receptors

SAPK-JNKStress-Activated Protein Kinase- c-Jun NH2-terminal Kinase.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-1-10 contains supplementary material, which is available to authorized users.

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Autor: Jason Y Chang - Ling-Zhi Liu


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