Back to Search
Start Over
Hypoxia-induced disruption of neural vascular barrier is mediated by the intracellular induction of Fe(II) ion
- Source :
- Experimental cell research. 379(2)
- Publication Year :
- 2018
-
Abstract
- Neural vascular barrier maintains the optimal tissue microenvironment of central nervous system in which neural cells can function normally. In various neural diseases, the decrease in oxygen concentration, hypoxia, of affected tissues is known to accelerate the disease progression through disruption of neural vascular barrier. Therefore, the clarification of mechanisms underlying hypoxia-induced disruption of neural vascular barrier would definitely lead to the establishment of new effective therapies for intractable neural diseases. In the present study, we first found that hypoxia disrupts neural vascular barrier through pathways independent of HIF-1α and HIF-2α. Then, with a specific fluorescence probe for ferrous, Fe(II) ion, we have obtained the interesting data showing that hypoxia increased the intracellular level of Fe(II) ion in endothelial cells of our in vitro model for neural vascular barrier, and that hypoxia-induced disruption of neural vascular barrier could be inhibited by chelating Fe(II) ion in endothelial cells. Furthermore, in the presence of a reducing reagent for reactive oxygen species (ROS), hypoxia could not disrupt the neural vascular barrier despite that the hypoxic increase in intracellular level of Fe(II) ion was confirmed in endothelial cells. These results indicate that hypoxia-triggered increase in the level of intracellular Fe(II) ion and subsequent production of ROS, probably through Fenton reaction, are the essential pathway mediating the disruption of neural vascular barrier under hypoxia.
- Subjects :
- 0301 basic medicine
Cytoplasm
Iron
Central nervous system
Biology
Ion
Cell Line
03 medical and health sciences
0302 clinical medicine
medicine
Humans
NADH, NADPH Oxidoreductases
Hypoxia
chemistry.chemical_classification
Reactive oxygen species
Fenton reaction
Disease progression
Endothelial Cells
Cell Biology
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Cell Hypoxia
Cell biology
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Limiting oxygen concentration
medicine.symptom
Reactive Oxygen Species
Intracellular
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 379
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....f7fb6a5501a9eeba7191ddf40e1e3d9b