1. Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK/HO-1 pathway.
- Author
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Wu J, Zhao Y, Fan Z, Chen Q, Chen J, Sun Y, Jiang X, and Xiao Q
- Subjects
- 8,11,14-Eicosatrienoic Acid analogs & derivatives, 8,11,14-Eicosatrienoic Acid metabolism, AMP-Activated Protein Kinases metabolism, Animals, Blood-Brain Barrier metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Disease Models, Animal, Enzyme Inhibitors therapeutic use, Epoxide Hydrolases metabolism, Heme Oxygenase-1 metabolism, Male, Membrane Proteins metabolism, Mice, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Blood-Brain Barrier drug effects, Blood-Brain Barrier pathology, Diabetes Mellitus, Type 2 complications, Epoxide Hydrolases antagonists & inhibitors, Protective Agents therapeutic use
- Abstract
Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation., Competing Interests: Declaration of competing interest There is no conflict of interest among all authors. We also confirm that all the listed authors have participated actively in the study and approved the submitted manuscript. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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