title: Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro.
abstract: The study was performed to investigate the role of sonic hedgehog (SHH) in the oxidized low-density lipoprotein (oxLDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to oxLDL. The results indicated that treatment of MBMECs with oxLDL decreased the cell viability, and oxidative stress was involved in oxLDL-induce MBMECs dysfunction with increasing intracellular ROS and MDA formation as well as decreasing NO release and eNOS mRNA expression. In addition, SHH signaling components, such as SHH, Smo and Gli1, mRNA and protein levels were significantly decreased after incubation with increasing concentrations of oxLDL. Treatment with oxLDL alone or SHH loss-of-function significantly increased the permeability of MBMECs, and overexpression of SHH attenuated oxLDL-induced elevation of permeability in MBMECs. Furthermore, SHH gain-of-function could reverse oxLDL-induced apoptosis through inhibition caspase3 and caspase8 levels in MBMECs. Taken together, these results demonstrated that the suppression of SHH in MBMECs might contribute to the oxLDL-induced disruption of endothelial barrier. However, the overexpression of SHH could reverse oxLDL-induced endothelial cells dysfunction in vitro.
authors.affiliation: Department of Neurology, Provincial Clinic College of Fujian Medical University, Fujian Provincial Hospital Fuzhou 350001, China.
authors.forename: Xiu-Long
authors.initials: XL
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Provincial Clinic College of Fujian Medical University, Fujian Provincial Hospital Fuzhou 350001, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Neurology, Provincial Clinic College of Fujian Medical University, Fujian Provincial Hospital Fuzhou 350001, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein
keywords: Sonic hedgehog; blood-brain barrier; brain microvascular endothelial cells; oxidized low-density lipoprotein