Hypoxia-induced disruption of neural vascular barrier is mediated by the intracellular induction of Fe(II) ion

Dan Cui, Mitsuru Arima, Tasuku Hirayama, Eiji Ikeda

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)166-171
Number of pages6
JournalExperimental Cell Research
Volume379
Issue number2
DOIs
Publication statusPublished - Jun 15 2019

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Blood Vessels
Ions
Endothelial Cells
Reactive Oxygen Species
Hypoxia
Disease Progression
Central Nervous System
Fluorescence
Oxygen

All Science Journal Classification (ASJC) codes

  • Cell Biology

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Hypoxia-induced disruption of neural vascular barrier is mediated by the intracellular induction of Fe(II) ion. / Cui, Dan; Arima, Mitsuru; Hirayama, Tasuku; Ikeda, Eiji.

In: Experimental Cell Research, Vol. 379, No. 2, 15.06.2019, p. 166-171.

Research output: Contribution to journalArticle

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