Cytochemical study of the effect of aluminium on cultured brain microvascular endothelial cells.
The cytotoxic effect of aluminium was studied on cultured goat brain microvascular endothelial cells used as an in vitro model of the blood-brain barrier. Confluent monolayers of these cells were exposed for 4 days to aluminium maltol and, for control purposes, to maltol alone, and also to cadmium chloride as a known cytotoxic substance. The localization of plasmalemma-bound enzymatic activities of 5'-nucleotidase and Ca(2+)-ATPase and the distribution of sialic acid residues were studied at the ultrastructural level. It was observed that the reaction for 5'-nucleotidase activity was only insignificantly affected, indicating its resistance to the cytotoxic action of both substances used. On the contrary, the activity of Ca(2+)-ATPase was evidently suppressed, especially in the interendothelial clefts where junctional complexes are presumably to be formed. Aluminium also affects the density of sialic acid residues, as shown by their redistribution, leading to the appearance of relatively long segments of unlabelled apical cell surface. The data obtained suggest that observed changes in the localization of Ca(2+)-ATPase and sialic acid residues can lead ultimately to impairment of the formation and maintenance of intercellular junctions and to disturbances in the negatively charged domains of the endothelial cell surface. Whether these alterations, induced in vitro, contribute to in vivo disturbances of blood-brain barrier function requires further experimental study.
Vorbrodt
A W
AW
New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Trowbridge
R S
RS
Dobrogowska
D H
DH
D015720:5'-Nucleotidase / Q000032:analysis; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D002104:Cadmium / Q000633:toxicity; D019256:Cadmium Chloride; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D006041:Goats; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D019158:N-Acetylneuraminic Acid; D009942:Organometallic Compounds / Q000633:toxicity; D011753:Pyrones / Q000633:toxicity; D012794:Sialic Acids / Q000032:analysis
D002712:Chlorides; D009942:Organometallic Compounds; D011753:Pyrones; D012794:Sialic Acids; D002104:Cadmium; C067527:aluminum maltolate; C008316:maltol; D000535:Aluminum; D015720:5'-Nucleotidase; D000252:Calcium-Transporting ATPases; D019158:N-Acetylneuraminic Acid; D019256:Cadmium Chloride