title: Novel insights in the dysfunction of human blood-brain barrier after glycation.
abstract: The blood-brain barrier (BBB) provides a dynamic and complex interface consisting of endothelial cells, pericytes and astrocytes, which are embedded in a collagen and fibronectin-rich basement membrane. This complex structure restricts the diffusion of small hydrophilic solutes and macromolecules as well as the transmigration of leukocytes into the brain. It has been shown that carbonyl stress followed by the formation of advanced glycation endproducts (AGE=glycation) interfere with the BBB integrity and function. Here, we present data that carbonyl stress induced by methylglyoxal leads to glycation of endothelial cells and the basement membrane, which interferes with the barrier-function and with the expression of RAGE, occludin and ZO-1. Furthermore, methylglyoxal induced carbonyl stress promotes the expression of the pro-inflammatory interleukins IL-6 and IL-8. In summary, this study provides new insights into the relationship between AGE formation by carbonyl stress and brain microvascular endothelial barrier dysfunction.
authors.affiliation: Institute of Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Institute of Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bork
authors.affiliation: Institute of Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany.
authors.forename: Vinayaga S
authors.initials: VS
authors.lastname: Gnanapragassam
authors.affiliation: Institute of Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Bennmann
authors.affiliation: Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jacobs
authors.affiliation: Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Navarette-Santos
authors.affiliation: Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Britt
authors.initials: B
authors.lastname: Hofmann
authors.affiliation: Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.affiliation: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Danker
authors.affiliation: Institute of Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Salle), Germany. Electronic address: ruediger.horstkorte@medizin.uni-halle.de.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C508606:CXCL8 protein, human; D017127:Glycation End Products, Advanced; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C568985:OCLN protein, human; D062793:Occludin; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C498978:MOK protein, human; D020928:Mitogen-Activated Protein Kinases
keywords: Advanced glycation endproducts (AGEs); Blood-brain barrier; Extracellular matrix; Glycation; Interleukin