Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature.
Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular enrichment with glutathione. In the second series of experiments, rats were infused with nano-alumina at the dose of 29 mg/kg and the brains were stained for expression of tight junction proteins. Treatment with nano-alumina resulted in a marked fragmentation and disruption of integrity of claudin-5 and occludin. These results indicate that cerebral vasculature can be affected by nano-alumina. In addition, our data indicate that alterations of mitochondrial functions may be the underlying mechanism of nano-alumina toxicity.
Chen
Lei
L
Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky Medical Center, 593 Wethington Bldg., 900 S Limestone, Lexington, KY 40536, USA.
Yokel
Robert A
RA
Hennig
Bernhard
B
Toborek
Michal
M
D000537:Aluminum Oxide / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D062507:Claudin-5; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D055806:Microvessels / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D062793:Occludin; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D019108:Tight Junctions / Q000187:drug effects*
D000975:Antioxidants; D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D005978:Glutathione; D000537:Aluminum Oxide