Zinc deficiency alters barrier function of cultured porcine endothelial cells.
Zinc is necessary for normal membrane function and stability. We postulated that Zn deficiency may disrupt the integrity of the vascular endothelium by decreasing its barrier function. To test this hypothesis, endothelial cells were cultured on polycarbonate filters and exposed to media enriched with either 1% fetal bovine serum (FBS) (low FBS; total Zn, 1.07 mumols/L medium) or 5% FBS (control; total Zn, 2.29 mumols/L) or low FBS plus two supplemental levels of Zn, 3.36 and 5.66 mumols total zinc/L. Endothelial cell barrier function, expressed as albumin transfer across cultured endothelial monolayers, was significantly lower in cultures exposed to low FBS compared with control medium. Supplementation with 5.66 mumols total Zn/L completely restored endothelial barrier function. A divalent cation chelator, 1,10-orthophenanthroline, was used to induce Zn deficiency in vitro. Compared with control cultures, the presence of 1,10-orthophenanthroline in the culture medium resulted in markedly lower endothelial barrier function that was increased by the addition of Zn but not calcium or magnesium. Activity of the membrane-bound zinc-dependent angiotensin-converting enzyme (ACE) was depressed by low zinc medium, whereas membrane-bound Ca(2+)-ATPase and total ATPase were not depressed. Furthermore, cells cultivated in low zinc medium did not have greater cytosolic release of adenine, indicating no increase in cell injury or death. These data suggest that Zn is vital to endothelial cell integrity and that Zn may play an important role in vascular endothelial barrier function.
Hennig
B
B
Department of Nutrition and Food Science, University of Kentucky, Lexington.
Wang
Y
Y
Ramasamy
S
S
McClain
C J
CJ
D000225:Adenine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005312:Fetal Blood; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D013552:Swine; D015032:Zinc / Q000172:deficiency* / Q000502:physiology
D000418:Albumins; D007703:Peptidyl-Dipeptidase A; D000251:Adenosine Triphosphatases; D015032:Zinc; D000225:Adenine