Propofol improved hypoxia‐impaired integrity of blood‐brain barrier via modulating the expression and phosphorylation of zonula occludens‐1

Autor: Wei Chen, Xing‐Zhu Ju, Jiawei Chen, Yan Lu, Changhong Miao, Xiaowei Ding
Rok vydání: 2019
Předmět:
blood‐brain barrier
Vascular Endothelial Growth Factor A
0301 basic medicine
Pharmacology
Blood–brain barrier
Neuroprotection
Calcium in biology
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Physiology (medical)
Ca2+/calmodulin-dependent protein kinase
medicine
Animals
Pharmacology (medical)
Phosphorylation
Cells
Cultured
propofol
hypoxia
Endothelial Cells
Cardiovascular Agents
Original Articles
zonula occludens‐1
Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit
Cell Hypoxia
Coculture Techniques
Vascular endothelial growth factor
Psychiatry and Mental health
mouse brain microvascular endothelial cells
030104 developmental biology
medicine.anatomical_structure
nervous system
chemistry
Blood-Brain Barrier
Astrocytes
Microvessels
Zonula Occludens-1 Protein
cardiovascular system
Original Article
Calcium
medicine.symptom
Propofol
030217 neurology & neurosurgery
medicine.drug
Zdroj: CNS Neuroscience & Therapeutics
ISSN: 1755-5949
1755-5930
DOI: 10.1111/cns.13101
Popis: Summary Aims Hypoxia may damage blood‐brain barrier (BBB). The neuroprotective effect of propofol has been reported. We aimed to identify whether and how propofol improved hypoxia‐induced impairment of BBB integrity. Methods Mouse brain microvascular endothelial cells (MBMECs) and astrocytes were cocultured to establish in vitro BBB model. The effects of hypoxia and propofol on BBB integrity were examined. Further, zonula occludens‐1 (ZO‐1) expression and phosphorylation, hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF) expression, intracellular calcium concentration and Ca2+/calmodulin‐dependent protein kinase II (CAMKII) activation were measured. Results Hypoxia‐impaired BBB integrity, which was protected by propofol. Hypoxia‐reduced ZO‐1 expression, while induced ZO‐1 phosphorylation. These effects were attenuated by propofol. The expression of HIF‐1α and VEGF was increased by hypoxia and was alleviated by propofol. The hypoxia‐mediated suppression of ZO‐1 and impaired BBB integrity was reversed by HIF‐α inhibitor and VEGF inhibitor. In addition, hypoxia increased the intracellular calcium concentration and induced the phosphorylation of CAMKII, which were mitigated by propofol. The hypoxia‐induced phosphorylation of ZO‐1 and impaired BBB integrity was ameliorated by calcium chelator and CAMKII inhibitor. Conclusion Propofol could protect against hypoxia‐mediated impairment of BBB integrity. The underlying mechanisms may involve the expression and phosphorylation of ZO‐1.
Databáze: OpenAIRE
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