title: Phospholipid transfer protein (PLTP) deficiency impaired blood-brain barrier integrity by increasing cerebrovascular oxidative stress.
abstract: Phospholipid transfer protein (PLTP) regulates lipid metabolism and plays an important role in oxidative stress. PLTP is highly expressed in blood-brain barrier (BBB), but the role of PLTP in BBB integrity is not clear. In this study, BBB permeability was detected with in vivo multiphoton imaging and Evans blue assay. We found that PLTP deficient mice exhibited increased BBB permeability, as well as decreased expression of tight junction proteins occludin, zona occludens-1 (ZO-1) and claudin-5 in brain vessels. Cerebrovascular oxidative stress increased in PLTP deficient mice, including increased levels of reactive oxygen species (ROS) and lipid peroxidation marker 4-hydroxy-2-nonenal (HNE) and reduced superoxide dismutase (SOD) activity. Dietary supplementation of antioxidant vitamin E increased BBB integrity and tight junction proteins expression via reducing cerebrovascular oxidative stress. These findings indicated an essential role of PLTP in maintaining BBB integrity, possibly through its ability to transfer vitamin E, and modulate cerebrovascular oxidative stress.
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Ting
authors: T
authors: Zhou
authors: Center of Medical and Health Analysis, Peking University, Beijing, China.
authors: Qihua
authors: Q
authors: He
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Yawei
authors: Y
authors: Tong
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors: Rui
authors: R
authors: Zhan
authors: Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors: Feng
authors: F
authors: Xu
authors: Peking University Third Hospital, Beijing, China.
authors: Dongsheng
authors: D
authors: Fan
authors: Peking University Third Hospital, Beijing, China.
authors: Xiangyang
authors: X
authors: Guo
authors: Peking University Third Hospital, Beijing, China.
authors: Hongbin
authors: H
authors: Han
authors: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Shucun
authors: S
authors: Qin
authors: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China; Peking University Third Hospital, Beijing, China. Electronic address: dchui@bjmu.edu.cn.
authors: Dehua
authors: D
authors: Chui
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000098:blood supply; D062507:Claudin-5 / Q000032:analysis; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014810:Vitamin E / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000032:analysis
chemical_list: D062507:Claudin-5; D062793:Occludin; D049294:Phospholipid Transfer Proteins; D062826:Zonula Occludens-1 Protein; C510091:phospholipid transfer protein, mouse; D014810:Vitamin E
keywords: Blood–brain barrier; Oxidative stress; Phospholipid transfer protein; Tight junction