title: Fructose-1,6-bisphosphate ameliorates lipopolysaccharide-induced dysfunction of blood-brain barrier.
abstract: Fructose-1,6-bisphosphate (FBP), a glycolytic intermediate, has neuroprotective effects in various brain injury models. However, its effects on blood-brain barrier (BBB) are largely unknown. In this study, we investigated the effects of FBP on lipopolysaccharide (LPS)-induced BBB dysfunction in in vitro BBB model comprising co-culture of mouse brain endothelial cell line, bEnd.3 and mouse primary astrocyte and explored its action mechanism therein involved. LPS induced the impairment of endothelial permeability and transendothelial electrical resistance (TEER). The functional changes were confirmed by alterations in immunostaining for junctional proteins occludin, ZO-1 and VE-cadherin, such as the loss of cortical staining pattern and appearance of intercellular gaps in endothelial cells. Co-administration of FBP alleviated the deleterious effects of LPS on BBB permeability and TEER in a dose dependent manner. And also FBP inhibited the LPS-induced changes in the distribution of endothelial junctional proteins, resulting in the better preservation of monolayer integrity. FBP suppressed the production of reactive oxygen species (ROS) but did not affect cyclooxygenase-2 expression and prostaglandin E₂ production in endothelial cells stimulated with LPS. Taken together, these data suggest that FBP could ameliorate LPS-induced BBB dysfunction through the maintenance of junctional integrity, which might be mediated by downregulation of ROS production.
authors.affiliation: Department of Physiology, Ajou University School of Medicine, #5, Wonchon-dong, Suwon, 443-749, Republic of Korea.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Seok
authors.forename: Jae Mi
authors.initials: JM
authors.lastname: Kim
authors.forename: Tae Yeop
authors.initials: TY
authors.lastname: Park
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Baik
authors.forename: Soo Hwan
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005635:Fructosediphosphates / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D005635:Fructosediphosphates; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D062725:Tight Junction Proteins; C082161:lipopolysaccharide A; C029063:fructose-1,6-diphosphate