Fructose-1,6-bisphosphate ameliorates lipopolysaccharide-induced dysfunction of blood-brain barrier

Sun Mi Seok, Jae Mi Kim, Tae Yeop Park, Eun Joo Baik, Soo Hwan Lee

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1149-1159
Number of pages11
JournalArchives of Pharmacal Research
Volume36
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Blood-brain barrier
  • Fructose-1,6-bisphosphate
  • Lipopolysaccharide
  • Murine brain cerebrovascular endothelial cells
  • Permeability
  • Tight junction protein

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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