Korean J Physiol Pharmacol.  2016 Jul;20(4):325-332. 10.4196/kjpp.2016.20.4.325.

Resveratrol attenuates lipopolysaccharide-induced dysfunction of blood-brain barrier in endothelial cells via AMPK activation

Affiliations
  • 1Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China. hu15084737958@139.com
  • 2Deapartment of Orthopaedics, The Third Xiangya Hospital, Central South University, Changsha 410013, China. Liu1367251@163.com

Abstract

Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. 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. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS (1 µg/ml) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding 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 resveratrol. Finally, upregulation of AMPK by either AMPK-CA or resveratrol abolished the levels of LPS-enhanced NAD(P)H oxidase subunits protein expressions. We conclude that AMPK activation by resveratrol improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs.

Keyword

AMPK; Blood -brain barrier; LPS; NAD(P)H oxidase; Resveratrol

MeSH Terms

AMP-Activated Protein Kinases*
Blood-Brain Barrier*
Brain
Claudin-5
Endothelial Cells*
Homeostasis
Humans
NADPH Oxidase
Oxidoreductases
Permeability
Reactive Oxygen Species
Superoxide Dismutase
Tight Junctions
Up-Regulation
AMP-Activated Protein Kinases
Claudin-5
NADPH Oxidase
Oxidoreductases
Reactive Oxygen Species
Superoxide Dismutase
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