Cultured cells of the blood-brain barrier from apolipoprotein B-100 transgenic mice: effects of oxidized low-density lipoprotein treatment.

Abstract

BACKGROUND:

The apolipoprotein B-100 (ApoB-100) transgenic mouse line is a model of human atherosclerosis. Latest findings suggest the importance of ApoB-100 in the development of neurodegenerative diseases and microvascular/perivascular localization of ApoB-100 protein was demonstrated in the cerebral cortex of ApoB-100 transgenic mice. The aim of the study was to characterize cultured brain endothelial cells, pericytes and glial cells from wild-type and ApoB-100 transgenic mice and to study the effect of oxidized low-density lipoprotein (oxLDL) on these cells.

METHODS:

Morphology of cells isolated from brains of wild type and ApoB-100 transgenic mice was characterized by immunohistochemistry and the intensity of immunolabeling was quantified by image analysis. Toxicity of oxLDL treatment was monitored by real-time impedance measurement and lactate dehydrogenase release. Reactive oxygen species and nitric oxide production, barrier permeability in triple co-culture blood-brain barrier model and membrane fluidity were also determined after low-density lipoprotein (LDL) or oxLDL treatment.

RESULTS:

The presence of ApoB-100 was confirmed in brain endothelial cells, while no morphological change was observed between wild type and transgenic cells. Oxidized but not native LDL exerted dose-dependent toxicity in all three cell types, induced barrier dysfunction and increased reactive oxygen species (ROS) production in both genotypes. A partial protection from oxLDL toxicity was seen in brain endothelial and glial cells from ApoB-100 transgenic mice. Increased membrane rigidity was measured in brain endothelial cells from ApoB-100 transgenic mice and in LDL or oxLDL treated wild type cells.

CONCLUSION:

The morphological and functional properties of cultured brain endothelial cells, pericytes and glial cells from ApoB-100 transgenic mice were characterized and compared to wild type cells for the first time. The membrane fluidity changes in ApoB-100 transgenic cells related to brain microvasculature indicate alterations in lipid composition which may be linked to the partial protection against oxLDL toxicity.

• Authors: Nikolett Lénárt, Fruzsina R Walter, Alexandra Bocsik, Petra Sántha, Melinda E Tóth, András Harazin, Andrea E Tóth, Csaba Vizler, Zsolt Török, Ana-Maria Pilbat, László Vígh, László G Puskás, Miklós Sántha, Mária A Deli
• Journal: Fluids and barriers of the CNS (Fluids Barriers CNS) Vol. 12 Pg. 17 (Jul 17 2015) ISSN: 2045-8118 [Print] England
• PMID: 26184769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein B-100
• Lipoproteins, LDL
• Reactive Oxygen Species
• oxidized low density lipoprotein
• Nitric Oxide

Topics

• Animals
• Apolipoprotein B-100 (genetics, metabolism)
• Atherosclerosis (metabolism)
• Blood-Brain Barrier (cytology, drug effects, physiology)
• Cell Survival (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Lipoproteins, LDL (toxicity)
• Membrane Fluidity (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuroglia (drug effects, metabolism)
• Nitric Oxide (metabolism)
• Pericytes (drug effects, metabolism)
• Reactive Oxygen Species (metabolism)