JOURNAL ARTICLE

Isoflurane inhibits occludin expression via up-regulation of hypoxia-inducible factor 1α

Jingyu Zhao, Jianhua Hao, Xiang Fei, Xiaoyan Wang, Yinan Hou, Chengqi Deng
Brain Research 2014 May 8, 1562: 1-10
24661914

UNLABELLED: The blood-brain barrier (BBB) is a functional structure which regulates and restricts the transfer of circulating molecules and immune cells into the central nervous system. The barrier is formed by the presence of tight junctions (TJ) between the specialized brain endothelial cells. The volatile anesthetic isoflurane may affect the permeability of the BBB. Previous studies have proven that isoflurane alters hypoxia-inducible factor-1α (HIF-1α) expression, which may affect the TJ proteins; however, the mechanism of how TJ proteins are affected by isoflurane is still unclear. Primary human brain vascular endothelial cells (HBVEC) were exposed to isoflurane at various concentrations (0-2.5%) and different time periods (0-6 h). The cell viability, occludin expression, paracellular permeability, VEGF expression, TGF-β3 expression and occludin protein endocytosis were quantified. Isoflurane treatment induced a time- and concentration-dependent decrease in occludin mRNA and protein levels in HBVEC. This effect was partially abrogated by silencing the HIF-1α expression. Isoflurane could activate HIF-1α, and the overexpression HIF-1α up-regulated the level of VEGF and TGF-β3, VEGF decreased the expression of occludin and TGF-β3 accelerated the endocytosis of occludin. RNA interference targeting HIF-1α reduced both VEGF and TGF-β3 expression after isoflurane treatment.

CONCLUSION: This study provides direct evidence in vitro that exposing isoflurane to HBVECs can trigger HIF-1α activation, leading to lower protein levels of occludin, and increased permeability of the BBB.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
24661914
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"