We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Activation of AMPK attenuates lipopolysaccharide-impaired integrity and function of blood-brain barrier in human brain microvascular endothelial cells.
Experimental and Molecular Pathology 2014 December
The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. Lipopolysaccharide (LPS) is known to alter the integrity of the BBB in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying the disruption of the BBB in LPS-induced sepsis and to determine whether the activation of AMP-activated protein kinase (AMPK) prevents LPS-induced BBB dysfunction. The exposure of human brain microvascular endothelial cells (HBMECs) to LPS (1 μg/ml) for 4 to 24h a week dramatically increased the permeability of the BBB in parallel with the lowered expression levels of occludin and claudin-5, which are essential to maintain tight junctions in HBMECs. In addition, LPS significantly increased the reactive oxygen species (ROS) productions. All effects induced by LPS in HBVMCs were reversed by adenoviral overexpression of superoxide dismutase, inhibition of NAD(P)H oxidase by apocynin or gain-function of AMPK by adenoviral overexpression of constitutively active mutant (AMPK-CA) or by 5-amino-4-imidazole carboxamide riboside (AICAR). Finally, the upregulation of AMPK by either AMPK-CA or AICAR abolished the levels of LPS-enhanced NAD(P)H oxidase subunit protein expressions. We conclude that AMPK activation improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app