Role of benzylamine oxidase in the cytotoxicity of allylamine toward aortic smooth muscle cells.
In this study we demonstrate that by inhibiting benzylamine oxidase (BzAO) with either semicarbazide or phenelzine, aortic smooth muscle cells (ASMCs) are protected from cytolethal injury by the cardiovascular toxin allylamine. We find that although both semicarbazide and phenelzine inhibit BzAO or ASMCs grown in vitro, phenelzine is the more effective inhibitor. We further demonstrate that although semicarbazide--at concentrations inhibiting BzAO--protects ASMCs from cytolethal concentrations of allylamine, it does not fully protect ASMCs from sublethal injury as assessed by [3H]uridine uptake. In contrast, phenelzine appears to afford complete protection of ASMCs from allylamine injury. Although semicarbazide and phenelzine pretreatment does not interfere with [14C]allylamine uptake by ASMCs, retention time of the 14C-moiety from radiolabeled allylamine is less in pretreated ASMCs. Subcellular distribution studies of ASMCs exposed to [14C]allylamine demonstrate that inhibiting BzAO activity in ASMCs results in marked derangement of the distribution pattern of 14C-moiety in subcellular fractions of ASMCs, with 14C-moiety not localized to mitochondrial/endoplasmic reticulum enriched fractions.
D000499:Allylamine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D000588:Amines / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects; D001595:Benzylamine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010624:Phenelzine / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D012663:Semicarbazides / Q000494:pharmacology; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D013552:Swine; D014529:Uridine / Q000378:metabolism
D000588:Amines; D012663:Semicarbazides; D012642:Selegiline; C010059:carbamylhydrazine; D000499:Allylamine; D001595:Benzylamine Oxidase; D008995:Monoamine Oxidase; D010624:Phenelzine; D014529:Uridine