Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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.
Doi: 10.1016/j.biocel.2006.01.013
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Panzenboeck Ute
- Co-authors Med Uni Graz
- Bernhart Eva Maria
- Hammer Astrid
- Kratzer Ingrid
- Malle Ernst
- 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