S-adenosylhomocysteine as a physiological modulator of Apo-1-mediated apoptosis

Frank Ratter, Matthias Germer, Thomas Fischbach, Klaus Schulze-Osthoff, Marcus E. Peter, Wulf Dröge, Peter H. Krammer, Volker Lehmann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


APO-1/Fas (CD95) is a member of the tumor necrosis factor/nerve growth factor receptor superfamily and mediates apoptosis in various cell types. Here we show that L929 cells, expressing human APO-1 treated with agonistic antibodies (anti-APO-1), elicit an early and transient increase of S-adenosylhomocysteine (AdoHcy), a potent inhibitor of S-adenosylmethionine (AdoMet)-dependent methylation reactions. In contrast, anti-APO-1 did not induce an AdoHcy increase in L929-APO-1 Δ4 cells expressing a C-terminally truncated APO-1 lacking part of the 'death domain' known to be required for the transduction of apoptotic signals. Addition of adenosine and D,L-homocysteine also led to an increase of cellular AdoHcy thus enhancing anti-APO-1-induced killing of L929-APO-1 cells. Treatment with anti-APO-1 also induced release of arachidonic acid from phospholipids: this effect was augmented by elevated levels of AdoHcy. In contrast, AdoHcy had only a minor effect on anti-APO-1-mediated DNA fragmentation. These findings suggest that AdoHcy functions as a physiological modulator of APO-1-mediated cell death in L929 cells and enhances anti-APO-1-induced cell killing at least partially by acting via the phospholipase A2 pathway.

Original languageEnglish (US)
Pages (from-to)1139-1147
Number of pages9
JournalInternational Immunology
Issue number7
StatePublished - 1996


  • Adenosine
  • Anti-APO-1 antibody
  • Arachidonic acid
  • Cell death
  • D,L-homocysteine
  • DNA
  • Fragmentation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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