TNF but not linoleic acid stimulates multiple polyamine regulatory processes in cultured endothelial cells

Polyamines may be the intracellular signaling mechanisms which mediate specific responses induced by tumor necrosis factor-a (TNF) or linoleic acid (18:2) in endothelial cells. To explore this hypothesis, cellular polyamine metabolism and cellular oxidative stress were measured in cultured endothelial cells exposed to TNF or 18:2 and/or dimethylthiourea (DMTU) and/or vitamin E for up to 24 hours. Although both TNF and 18:2 increased cellular oxidation, only TNF but not 18:2 increased cellular levels and uptake of putrescine and spermidine in cultured endothelial cells. Treatment with TNF also increased endothelial cell activity and mRNA steady state levels of ornithine decarboxylase. DMTU attenuated both TNF-mediated oxidative stress and TNF-induced disturbances in polyamine metabolism. However, vitamin E, despite its antioxidant activity, increased TNF-mediated alterations in polyamine metabolism. These data indicate that polyamines may mediate TNFinduced cellular responses and that both upregulation of polyamine biosynthesis and transport are involved in this process. In addition, it appears that TNF-induced changes in polyamine metabolism are not solely dependent on increased oxidative stress. (Supported in part by NIH HL36552. AHA, and KY Ag. Exp. Station Funds).