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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
Phospholipid transfer protein (PLTP) deficiency impaired blood-brain barrier integrity by increasing cerebrovascular
Ting Zhou1, Qihua He2, Yawei Tong1
1Neuroscience 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.
Insights
Phospholipid transfer protein (PLTP) deficiency increases blood-brain barrier (BBB) permeability and oxidative stress. PLTP may maintain BBB integrity by transferring vitamin E and reducing oxidative stress.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Phospholipid transfer protein (PLTP) is involved in lipid metabolism and oxidative stress.
- PLTP is highly expressed in the blood-brain barrier (BBB), but its role in BBB integrity is unknown.
Purpose of the Study:
- To investigate the role of PLTP in maintaining blood-brain barrier integrity.
- To explore the mechanisms underlying PLTP's function in the BBB.
Main Methods:
- In vivo multiphoton imaging and Evans blue assay were used to assess BBB permeability.
- Expression of tight junction proteins (occludin, ZO-1, claudin-5) was analyzed.
- Cerebrovascular oxidative stress markers (ROS, HNE, SOD activity) were measured.
Main Results:
- PLTP-deficient mice showed increased BBB permeability and reduced expression of tight junction proteins.
- PLTP deficiency led to increased cerebrovascular oxidative stress (ROS, HNE) and decreased antioxidant activity (SOD).
- Vitamin E supplementation improved BBB integrity and tight junction protein expression in PLTP-deficient mice.
Conclusions:
- PLTP plays a crucial role in maintaining blood-brain barrier integrity.
- PLTP may exert its protective effects by facilitating vitamin E transfer and mitigating 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.
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