Nitric oxide protects blood‐brain barrier in vitro from hypoxia/reoxygenation‐mediated injury

FEBS Letters

Paul, Martin²  Tenz, Kareen¹  Utepbergenov, Darkhan I³  Sporbert, Anje¹  Haseloff, Reiner F¹  Blasig, Ingolf E¹  Mertsch, Katharina¹ 

[1] Forschungsinstitut für Molekulare Pharmakologie, Alfred-Kowalke-Str. 4, D-10315 Berlin, Germany;Institut für Klinische Pharmakologie, Freie Universität, 12200 Berlin, Germany;Institute of Chemical Kinetics and Combustion, Novosibirsk 630090, Russia

关键词: Nitric oxide;    Blood-brain barrier;    Hypoxia;    Endothelial cell;    Lipid peroxidation;    Oxygen radical;   

DOI  :  10.1016/S0014-5793(98)00173-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A cell culture model of blood-brain barrier (BBB, coculture of rat brain endothelial cells with rat astrocytes) was used to investigate the effect of nitric oxide (^⋅NO) on the damage of the BBB induced by hypoxia/reoxygenation (H/R). Permeability coefficient of fluorescein across the endothelium was used as a marker of BBB tightness. The permeability coefficient increased 5.2 times after H/R indicating strong disruption of the BBB. The presence of the ^⋅NO donor S-nitroso-N-acetylpenicillamine (SNAP, 30 μM), authentic ^⋅NO (6 μM) or superoxide dismutase (50 units/ml) during H/R attenuated H/R-induced increase in permeability. 30 μM SNAP or 6 μM ^⋅NO did not influence the function of BBB during normoxia, however, severe disruption was observed using 150 μM of SNAP and more than 24 μM of ^⋅NO. After H/R of endothelial cells, the content of malondialdehyde (MDA) increased 2.3 times indicating radical-induced peroxidation of membrane lipids. 30 μM SNAP or 6 μM authentic ^⋅NO completely prevented MDA formation. The results show that ^⋅NO may effectively scavenge reactive oxygen species formed during H/R of brain capillary endothelial cells, affording protection of BBB at the molecular and functional level.

【 授权许可】

Unknown