Oxidized polyamines and the growth of human vascular endothelial cells. Prevention of cytotoxic effects by selective acetylation.
The responses of human umbilical-vein vascular endothelial cells in culture to the naturally occurring polyamines spermine, spermidine and putrescine, their acetyl derivatives and oxidation products were examined. In the absence of human polyamine oxidase, exposure of cells to polyamines (up to 160 microM) had no adverse effects. In the presence of polyamine oxidase, spermine and spermidine were cytotoxic, but putrescine was not. Acetylation of the aminopropyl group of spermidine or both aminopropyl groups of spermine prevented this cytotoxicity. The amino acids corresponding to the polyamines, representing a further stage of oxidation, were also without effect. The cytotoxic effects were irreversible. Use of bovine serum amine oxidase in place of the human enzyme gave qualitatively similar results.
D000107:Acetylation; D006631:Amine Oxidase (Copper-Containing); D000596:Amino Acids / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D046911:Macromolecular Substances; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism; D000097667:Polyamine Oxidase
D006631:Amine Oxidase (Copper-Containing); D000596:Amino Acids; D007930:Leucine; D046911:Macromolecular Substances; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D013095:Spermidine; D013096:Spermine; D000097667:Polyamine Oxidase