Transglutaminase activity is involved in polyamine-induced programmed cell death

Francesco Facchiano, Daniela D'Arcangelo, Antonella Riccomi, Alessandro Lentini, Simone Beninati, Maurizio C. Capogrossi

Research output: Contribution to journalArticlepeer-review


Natural polyamines, i.e., putrescine, spermidine, and spermine, are ubiquitous molecules essential for cell proliferation and differentiation. In the present study, the effect of polyamines on primary cultures of bovine aortic 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 spermidine and spermine, at concentrations close to physiologic levels, induced a dose-dependent cell death, whereas putrescine was ineffective. RASMCs were significantly more sensitive than other cells. FACS analysis, oligonucleosome ELISA, Hoechst nuclear staining, and Annexin V-FITC quantification showed that cell death was likely due to apoptosis. Cells exposed to spermidine showed a marked increase of intracellular transglutaminase (TGase) activity (∼30-fold over control). Inhibitors of polyamine oxidation or inhibitors of TGase activity prevented polyamine-induced apoptosis. Moreover, tissue TGase overexpression significantly increased cell sensitivity to polyamine, suggesting that this effect is likely related to enhanced intracellular TGase activity. These data indicate that polyamines may modulate cell viability through a novel TGase-dependent process.

Original languageEnglish
Pages (from-to)118-129
Number of pages12
JournalExperimental Cell Research
Issue number1
Publication statusPublished - Nov 15 2001


  • Angiogenesis
  • Apoptosis
  • Melanoma cell
  • Polyamine
  • Programmed cell death
  • Transglutaminase
  • Vascular cells

ASJC Scopus subject areas

  • Cell Biology


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