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Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells

Cardoso, Filipa L ; Kittel, Agnes ; Veszelka, Szilvia ; Palmela, Inês ; Tóth, Andrea ; Brites, Dora ; Deli, Mária A ; Brito, Maria A Csermely, Peter

PloS one, 2012-05, Vol.7 (5), p.e35919 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells
Autor: Cardoso, Filipa L ; Kittel, Agnes ; Veszelka, Szilvia ; Palmela, Inês ; Tóth, Andrea ; Brites, Dora ; Deli, Mária A ; Brito, Maria A
Csermely, Peter
Assuntos: Albumin ; Analysis ; Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Aqueous solutions ; Astrocytes ; Astrocytes - drug effects ; Astrocytes - ultrastructure ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; beta Catenin - metabolism ; Bilirubin ; Bilirubin - pharmacology ; Biochemistry ; Biology ; Biophysics ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - ultrastructure ; Brain - blood supply ; Brain - metabolism ; Brain damage ; Brain injury ; Brain research ; Carbon monoxide ; Caveolae ; Cell adhesion & migration ; Cell death ; Cell Membrane Permeability - drug effects ; Cells, Cultured ; Claudin-5 ; Claudins - metabolism ; Coculture Techniques ; Cytokines ; Electric contacts ; Electrical junctions ; Electron microscopy ; Endoplasmic reticulum ; Endoplasmic Reticulum, Rough - drug effects ; Endothelial cells ; Endothelial Cells - drug effects ; Endothelial Cells - ultrastructure ; Endothelium ; Enlargement ; Exposure ; Glycoproteins ; Health risks ; Human serum albumin ; Impairment ; Integrity ; Invaginations ; Jaundice ; Laboratories ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Matrix metalloproteinases ; Medicine ; Membrane Proteins - metabolism ; Microscopy, Electron, Transmission ; Microvasculature ; Microvessels - drug effects ; Microvessels - ultrastructure ; Mitochondria ; Mitochondria - drug effects ; Mitogens ; Neonates ; Neurobiology ; Neurosciences ; Neurotoxicity ; Neurotoxins ; Nitric oxide ; P-Glycoprotein ; Permeability ; Pharmaceutical sciences ; Pharmacy ; Phosphoproteins - metabolism ; Proteins ; Rats ; Risk management ; Rodents ; Sepsis ; Serum albumin ; Toxicity ; Toxins ; Transmission electron microscopy ; Tumor necrosis factor-TNF ; Vascular endothelial growth factor ; Zonula Occludens-1 Protein ; β-Catenin
É parte de: PloS one, 2012-05, Vol.7 (5), p.e35919
Notas: Conceived and designed the experiments: MAB DB MAD. Performed the experiments: FLC ÁK SV IP AT. Analyzed the data: FLC MAB MAD. Contributed reagents/materials/analysis tools: MAB ÁK MAD. Wrote the paper: FLC MAB DB MAD. Implemented protocols: FLC ÁK SV IP AT. Contributed financial support/reagents/materials/analysis tools: MAB ÁK MAD. Drafted and edited the manuscript: FLC MAB DB ÁK SV MAD.
Descrição: Sepsis and jaundice are common conditions in newborns that can lead to brain damage. Though lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB), little is known on the effects of unconjugated bilirubin (UCB) and even less on the joint effects of UCB and LPS on brain microvascular endothelial cells (BMEC). Monolayers of primary rat BMEC were treated with 1 µg/ml LPS and/or 50 µM UCB, in the presence of 100 µM human serum albumin, for 4 or 24 h. Co-cultures of BMEC with astroglial cells, a more complex BBB model, were used in selected experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic-like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation of matrix metalloproteinases-2 and -9 in mono-cultures. Transmission electron microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and increased caveolae-like invaginations were noticeable in LPS-treated cells and loss of intercellular junctions was observed upon treatment with UCB. Both compounds triggered impairment of endothelial permeability and transendothelial electrical resistance both in mono- and co-cultures. The functional changes were confirmed by alterations in immunostaining for junctional proteins β-catenin, ZO-1 and claudin-5. Enlargement of intercellular spaces, and redistribution of junctional proteins were found in BMEC after exposure to LPS and UCB. LPS and/or UCB exert direct toxic effects on BMEC, with distinct temporal profiles and mechanisms of action. Therefore, the impairment of brain endothelial integrity upon exposure to these neurotoxins may favor their access to the brain, thus increasing the risk of injury and requiring adequate clinical management of sepsis and jaundice in the neonatal period.
Editor: United States: Public Library of Science
Idioma: Inglês

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Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells

Cardoso, Filipa L ; Kittel, Agnes ; Veszelka, Szilvia ; Palmela, Inês ; Tóth, Andrea ; Brites, Dora ; Deli, Mária A ; Brito, Maria A Csermely, Peter

United States: Public Library of Science

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