4-Hydroxynonenal impairs the permeability of an in vitro rat blood-brain barrier.
The function of the blood-brain barrier (BBB) can be impaired by free radicals. Since free radicals have only a limited diffusion capacity, we tested the possibility whether one of the major secondary lipid peroxidation product - 4-hydroxynonenal, is able to influence the permeability of the BBB. Therefore, we established an in vitro BBB model and tested its capacity to degrade 4-hydroxynonenal. Although, endothelial cells and astrocytes, possess the ability to degrade 4-hydroxynonenal the aldehyde is able to increase the permeability of the BBB. Since aldehydic lipid peroxidation products are metabolized via conjugation with glutathione we proofed that a decrease in glutathione is also able to increase the permeability of the BBB. We concluded that 4-hydroxynonenal is able to impair the BBB function via the decrease of reduced glutathione.
Mertsch
K
K
Max Delbrück Center of Molecular Medicine, Robert Rossle Str. 10, 13092 Berlin, Germany.
Blasig
I
I
Grune
T
T
D000447:Aldehydes / Q000493:pharmacokinetics*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D005609:Free Radicals; D005978:Glutathione; C027576:4-hydroxy-2-nonenal