Lipopolysaccharide-induced necroptosis of brain microvascular endothelial cells can be prevented by inhibition of endothelin receptors

Title:

Lipopolysaccharide-induced necroptosis of brain microvascular endothelial cells can be prevented by inhibition of endothelin receptors

Creator:

Abdul, Y., Ward, R., Ergul, A., and Dong, G.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:218a016e-1efc-4231-827a-23a284ed5958
uuid:218a016e-1efc-4231-827a-23a284ed5958
issn:0862-8408

Subject:

fyziologie člověka, human physiology, LPS, Necroptosis, Apoptosis, Ferroptosis, Endothelin, 14, and 612

Type:

model:article and TEXT

Format:

print, bez média, and svazek

Description:

Over activation of the endothelin-1 (ET-1) system in disease states contributes to endothelial dysfunction. On the other hand, ET-1 promotes proliferation and survival of endothelial cells. Regulation of programmed cell death (PCD) pathways is critical for cell survival. Recently discovered necroptosis (regulated necrosis) is a pathological PCD mechanism mediated by the activation of toll like receptor 4 (TLR4), which also happens to stimulate ET-1 production in dendritic cells. To establish the effect of ET-1 on PCD and survival of human brain microvascular endothelial cells (BMVECs) under control and inflammatory conditions, BMVECs were treated with ET-1 (10 nM, 100 nM and 1 μM) or lipopolysaccharide (LPS, 100 ng/ml). ET receptors were blocked with bosentan (10 μM). Under normal growth conditions, exogenous ET-1 reduced BMVEC viability and migration at a relatively high concentration (1 μM). This was accompanied with activation of necroptosis and apoptosis marker genes. LPS decreased endogenous ET-1 secretion, increased ETB receptor expression and activated necroptosis. Even though ET-1 levels were low (less than 10 nM levels used under normal growth conditions), blocking of ET receptors with bosentan inhibited the necroptosis pathway and improved the cell migration ability of BMVECs, suggesting that under inflammatory conditions, ET-1 activates PCD pathways in BMVECs even at physiological levels., Y. Abdul, R. Ward, G. Dong, A. Ergul., and Seznam literatury

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:Suppl 1

Harvested from:

CDK

Metadata only:

false