Transglutaminase activity is involved in polyamine-induced programmed celldeath

Natural polyamines, i.e., putrescine, spermidine, and spermine, are ubiquit ous molecules essential for cell proliferation and differentiation. In the present study, the effect of polyamines on primary cultures of bovine aorti c endothelial cells (BAECs), rat aortic smooth muscle cells (RASMCs), and a human melanoma cell line was examined. While in the absence of fetal calf serum (FCS) polyamines had no effect on viability, in the presence of FCS s permidine and spermine, at concentrations close to physiologic levels, indu ced a dose-dependent cell death, whereas putrescine was ineffective. RASMCs were significantly more sensitive than other cells. FACS analysis, oligonu cleosome ELISA, Hoechst nuclear staining, and Annexin V-FITC quantification showed that cell death was likely due to apoptosis. Cells exposed to sperm idine showed a marked increase of intracellular transglutaminase (TGase) ac tivity (similar to 30-fold over control). Inhibitors of polyamine oxidation or inhibitors of TGase activity prevented polyamine-induced apoptosis. Mor eover, tissue TGase overexpression significantly increased cell sensitivity to polyamine, suggesting that this effect is likely related to enhanced in tracellular TGase activity. These data indicate that polyamines may modulat e cell viability through a novel TGase-dependent process. (C) 2001 Academic Press.