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SHR Neuro Krebs Kardio Lipid

Panzenboeck, U; Kratzer, I; Sovic, A; Wintersperger, A; Bernhart, E; Hammer, A; Malle, E; Sattler, W.
Regulatory effects of synthetic liver X receptor- and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells.
Int J Biochem Cell Biol. 2006; 38(8): 1314-1329.
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Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Hammer Astrid
Kratzer Ingrid
Malle Ernst
Panzenboeck Ute
Sattler Wolfgang
Wintersperger Andrea
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Abstract:
The blood-brain barrier contributes to maintain brain cholesterol metabolism and protects this uniquely balanced system from exchange with plasma lipoprotein cholesterol. Brain capillary endothelial cells, representing a physiological barrier to the central nervous system, express apolipoprotein A-I (apoA-I, the major high-density lipoprotein (HDL)-associated apolipoprotein), ATP-binding cassette transporter A1 (ABCA1), and scavenger receptor, class B, type I (SR-BI), proteins that promote cellular cholesterol mobilization. Liver X receptors (LXRs) and peroxisome-proliferator activated receptors (PPARs) are regulators of cholesterol transport, and activation of LXRs and PPARs has potential therapeutic implications for lipid-related neurodegenerative diseases. To clarify the functional impact of LXR/PPAR activation, sterol transport along the: (i) ABCA1/apoA-I and (ii) SR-BI/HDL pathway was investigated in primary, polarized brain capillary endothelial cells, an in vitro model of the blood-brain barrier. Activation of LXR (24(S)OH-cholesterol, TO901317), PPARalpha (bezafibrate, fenofibrate), and PPARgamma (troglitazone, pioglitazone) modulated expression of apoA-I, ABCA1, and SR-BI on mRNA and/or protein levels without compromising transendothelial electrical resistance or tight junction protein expression. LXR-agonists and troglitazone enhanced basolateral-to-apical cholesterol mobilization in the absence of exogenous sterol acceptors. Along with the induction of cell surface-located ABCA1, several agonists enhanced cholesterol mobilization in the presence of exogenous apoA-I, while efflux of 24(S)OH-cholesterol (the major brain cholesterol metabolite) in the presence of exogenous HDL remained unaffected. Summarizing, in cerebrovascular endothelial cells apoA-I, ABCA1, and SR-BI represent drug targets for LXR and PPAR-agonists to interfere with cholesterol homeostasis at the periphery of the central nervous system.
Find related publications in this database (using NLM MeSH Indexing)
ATP-Binding Cassette Transporters - genetics
Animals - genetics
Apolipoprotein A-I - genetics
Biological Transport - drug effects
Cell Polarity - physiology
Cells, Cultured - physiology
Clofibric Acid - chemical synthesis
DNA-Binding Proteins - agonists
Endothelium, Vascular - cytology
Immunoblotting - cytology
Lipoproteins, HDL - metabolism
Lipoproteins, HDL3 - metabolism
Microscopy, Fluorescence - metabolism
Models, Biological - metabolism
Peroxisome Proliferator-Activated Receptors - agonists
RNA, Messenger - genetics
Receptors, Cytoplasmic and Nuclear - agonists
Scavenger Receptors, Class B - genetics
Signal Transduction - drug effects
Sterols - chemistry
Swine - chemistry
Thiazolidinediones - chemical synthesis
Transcription, Genetic - drug effects

Find related publications in this database (Keywords)
blood-brain barrier
nuclear receptors
ABCA1
ApoA-I
SR-BI
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