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

Nikolett Lénárt, Fruzsina R. Walter, Alexandra Bocsik, Petra Sántha, Melinda E. Tóth, András Harazin, Andrea E. Tóth, C. Vízler, Z. Török, Ana Maria Pilbat, L. Vígh, L. Puskás, M. Sántha, M. Deli

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article number17
JournalFluids and Barriers of the CNS
Volume12
Issue number1
DOIs
Publication statusPublished - Jul 17 2015

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Apolipoprotein B-100
Blood-Brain Barrier
Transgenic Mice
Cultured Cells
Endothelial Cells
Brain
LDL Lipoproteins
Therapeutics
Neuroglia
Pericytes
Membrane Fluidity
Reactive Oxygen Species
oxidized low density lipoprotein
Coculture Techniques
Microvessels
Electric Impedance
L-Lactate Dehydrogenase
Neurodegenerative Diseases
Cerebral Cortex
Permeability

Keywords

  • Apolipoprotein B-100
  • Blood-brain barrier
  • Brain endothelial cell
  • Glial cell
  • Membrane fluidity
  • Oxidized low density lipoprotein
  • Pericyte
  • Permeability
  • Reactive oxygen species
  • Transgenic mouse

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Developmental Neuroscience

Cite this

Cultured cells of the blood-brain barrier from apolipoprotein B-100 transgenic mice : Effects of oxidized low-density lipoprotein treatment. / Lénárt, Nikolett; Walter, Fruzsina R.; Bocsik, Alexandra; Sántha, Petra; Tóth, Melinda E.; Harazin, András; Tóth, Andrea E.; Vízler, C.; Török, Z.; Pilbat, Ana Maria; Vígh, L.; Puskás, L.; Sántha, M.; Deli, M.

In: Fluids and Barriers of the CNS, Vol. 12, No. 1, 17, 17.07.2015.

Research output: Contribution to journalArticle

Lénárt, Nikolett ; Walter, Fruzsina R. ; Bocsik, Alexandra ; Sántha, Petra ; Tóth, Melinda E. ; Harazin, András ; Tóth, Andrea E. ; Vízler, C. ; Török, Z. ; Pilbat, Ana Maria ; Vígh, L. ; Puskás, L. ; Sántha, M. ; Deli, M. / Cultured cells of the blood-brain barrier from apolipoprotein B-100 transgenic mice : Effects of oxidized low-density lipoprotein treatment. In: Fluids and Barriers of the CNS. 2015 ; Vol. 12, No. 1.
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AU - Bocsik, Alexandra

AU - Sántha, Petra

AU - Tóth, Melinda E.

AU - Harazin, András

AU - Tóth, Andrea E.

AU - Vízler, C.

AU - Török, Z.

AU - Pilbat, Ana Maria

AU - Vígh, L.

AU - Puskás, L.

AU - Sántha, M.

AU - Deli, M.

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N2 - 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.

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KW - Reactive oxygen species

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