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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Chirackal Manavalan, AP; Kober, A; Metso, J; Lang, I; Becker, T; Hasslitzer, K; Zandl, M; Fanaee-Danesh, E; Pippal, JB; Sachdev, V; Kratky, D; Stefulj, J; Jauhiainen, M; Panzenboeck, U.
Phospholipid transfer protein is expressed in cerebrovascular endothelial cells and involved in high density lipoprotein biogenesis and remodeling at the blood-brain barrier.
J Biol Chem. 2014; 289(8):4683-4698 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Becker Tatjana
Chirackal Manavalan Anil Paul
Fanaee-Danesh Elham
Kober Alexandra
Kratky Dagmar
Lang-Olip Ingrid
Panzenboeck Ute
Pippal Jyotsna Brijesh
Sachdev Vinay
Stefulj Jasminka
Zandl-Lang Martina

Dimensions Citations:

Plum Analytics:
Number of Figures: 9
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Phospholipid transfer protein (PLTP) is a key protein involved in biogenesis and remodeling of plasma HDL. Several neuroprotective properties have been ascribed to HDL. We reported earlier that liver X receptor (LXR) activation promotes cellular cholesterol efflux and formation of HDL-like particles in an established in vitro model of the blood-brain barrier (BBB) consisting of primary porcine brain capillary endothelial cells (pBCEC). Here, we report PLTP synthesis, regulation, and its key role in HDL metabolism at the BBB. We demonstrate that PLTP is highly expressed and secreted by pBCEC. In a polarized in vitro model mimicking the BBB, pBCEC secreted phospholipid-transfer active PLTP preferentially to the basolateral ("brain parenchymal") compartment. PLTP expression levels and phospholipid transfer activity were enhanced (up to 2.5-fold) by LXR activation using 24(S)-hydroxycholesterol (a cerebral cholesterol metabolite) or TO901317 (a synthetic LXR agonist). TO901317 administration elevated PLTP activity in BCEC from C57/BL6 mice. Preincubation of HDL3 with human plasma-derived active PLTP resulted in the formation of smaller and larger HDL particles and enhanced the capacity of the generated HDL particles to remove cholesterol from pBCEC by up to 3-fold. Pre-β-HDL, detected by two-dimensional crossed immunoelectrophoresis, was generated from HDL3 in pBCEC-derived supernatants, and their generation was markedly enhanced (1.9-fold) upon LXR activation. Furthermore, RNA interference-mediated PLTP silencing (up to 75%) reduced both apoA-I-dependent (67%) and HDL3-dependent (30%) cholesterol efflux from pBCEC. Based on these findings, we propose that PLTP is actively involved in lipid transfer, cholesterol efflux, HDL genesis, and remodeling at the BBB.
Find related publications in this database (using NLM MeSH Indexing)
Amyloid beta-Peptides - chemistry
Animals -
Apolipoprotein A-I - metabolism
Biological Transport -
Blood-Brain Barrier - cytology
Capillaries - cytology
Cell Polarity -
Cholesterol - metabolism
Endothelial Cells - metabolism
Gene Silencing -
Humans -
Lipoproteins, HDL - biosynthesis
Male -
Mice -
Mice, Inbred C57BL -
Models, Biological -
Orphan Nuclear Receptors - agonists
Phospholipid Transfer Proteins - metabolism
Protein Structure, Quaternary -
Sus scrofa -
Up-Regulation -

Find related publications in this database (Keywords)
Nuclear Receptors
Blood-Brain Barrier
Cholesterol Efflux
Pre- HDL
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