Fas‐induced programmed cell death is mediated by a Ras‐regulated O2 synthesis

E Gulbins, B Brenner, K Schlottmann, J Welsch… - …, 1996 - Wiley Online Library
E Gulbins, B Brenner, K Schlottmann, J Welsch, H Heinle, U Koppenhoefer, O Linderkamp…
Immunology, 1996Wiley Online Library
Fas induces apoptosis in lymphocytes via a poorly defined intracellular signalling cascade.
Previously, we have demonstrated the involvement and significance of a signalling cascade
from the Fas receptor via sphingomyelinases and ceramide to Ras in Fas‐induced
apoptosis. Here we demonstrate rapid and transient synthesis of reactive oxygen
intermediates (ROI) via activation of Ras after Fas. Genetic inhibition of Ras by transfection
of transdominant inhibitory N17Ras blocked Fas‐mediated ROI synthesis and programmed …
Fas induces apoptosis in lymphocytes via a poorly defined intracellular signalling cascade. Previously, we have demonstrated the involvement and significance of a signalling cascade from the Fas receptor via sphingomyelinases and ceramide to Ras in Fas‐induced apoptosis. Here we demonstrate rapid and transient synthesis of reactive oxygen intermediates (ROI) via activation of Ras after Fas. Genetic inhibition of Ras by transfection of transdominant inhibitory N17Ras blocked Fas‐mediated ROI synthesis and programmed cell death. Likewise, the antioxidants N‐acetyl‐cysteine and N‐t‐butyl‐phenylnitrone abolished Fas‐induced cell death, pointing to an important role for Ras‐triggered ROI synthesis in Fas‐mediated programmed cell death.
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