Chelation of intracellular iron enhances endothelial barrier function: a role for vitamin C?
Ascorbic acid improves endothelial barrier function by decreasing the permeability of endothelial cells cultured on semi-porous membrane filters. This decrease was not due to enhanced collagen synthesis and was mimicked by the collagen synthesis inhibitor ethyl-3,4-dihydroxybenzoic acid (EDHB). Since EDHB is known to chelate intracellular free iron, the effects of two membrane-permeant iron chelators were tested on endothelial permeability. Both 2,2'-dipyridyl and desferrioxamine decreased trans-endothelial permeability in a concentration-dependent manner. Increasing intracellular iron with a chelate of 8-hydroxyquinoline and ferric iron prevented effects of both EDHB and intracellular ascorbate. That EDHB and ascorbate did in fact chelate intracellular iron was supported by finding that they both decreased the cellular fluorescence quenching of the iron-sensitive dye Phen green SK. These results show that chelation of intracellular iron decreases endothelial barrier permeability and implicate this mechanism in the ability of EDHB and possibly intracellular ascorbate to tighten the endothelial barrier.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, United States. james.may@vanderbilt.edu
James M
JM
May
Zhi-chao
ZC
Qu
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D005456:Fluorescent Dyes; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D007444:Inulin / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D009930:Organic Chemicals; D015125:Oxyquinoline / Q000494:pharmacology
D005456:Fluorescent Dyes; D062385:Hydroxybenzoates; D007502:Iron Chelating Agents; D009930:Organic Chemicals; C431805:Phen Green SK; D003571:Cytochalasin B; C018063:ethyl protocatechuate; D015082:2,2'-Dipyridyl; D015125:Oxyquinoline; D007444:Inulin; D003094:Collagen; D007501:Iron; D005978:Glutathione; D003676:Deferoxamine; D001205:Ascorbic Acid; D003078:Colchicine