The tight junction proteins ZO-1, occludin and actin participate in the permeability increasing of blood-brain barrier induced by hypoxia-ischemia.
- Author:
Li-Wen WU
1
;
Fei YIN
;
Jing PENG
;
Wei-Dong WANG
;
Na GAN
Author Information
- Publication Type:Journal Article
- MeSH: Actins; analysis; physiology; Animals; Blood-Brain Barrier; Female; Hypoxia; metabolism; Ischemia; metabolism; Male; Membrane Proteins; analysis; physiology; Occludin; Permeability; Phosphoproteins; analysis; physiology; Rats; Rats, Sprague-Dawley; Tight Junctions; ultrastructure; Zonula Occludens-1 Protein
- From: Chinese Journal of Contemporary Pediatrics 2008;10(4):513-516
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the changes of blood-brain barrier-tight junction (BBB-TJ) proteins ZO-1, occludin and actin following hypoxia-ischemia (HI) in order to explore the possible mechanism of permeability increasing of blood-brain barrier (BBB) induced by HI.
METHODSBBB models were established by co-culture of cell ECV304 and astrocytes (AS) in vitro, then randomly assigned to control and HI groups. Transmission electron microscope was used to observe the changes of BBB-TJ. The distribution of actin was determined by direct-immunofluorescence microscope. Definite permeability of BBB models by 125I-BSA was detected by gamma events-per-unit-time meter. Expression of actin, ZO-1 and occludin was detected by Western blot.
RESULTSAfter 10-day culture, endothelial cells connected tightly, with plenty of TJ which was smooth, continuous and of high density, in the BBB models. After 5 hrs of HI, the TJ was opened with intercellular gaps formation. The direct immunofluorescence showed that the peripheral filament bands became blurred, the cell-cell junction loosened and fissure appeared in the HI group. The permeability of 125I-BSA in the HI group increased significantly compared with the control group (P<0.01). Expression of ZO-1 decreased markedly, while expression of actin and occludin was not different in the HI group compared with the control group.
CONCLUSIONSThe changes in occludin distribution and decreased expression of ZO-1 lead the reorganization of BBB-actin protein, which may be one of the mechanisms of permeability increasing of BBB following HI.