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Nitric oxide inhibits APO-1/Fas-mediated cell death
S Dimmeler1, J Haendeler, A Sause
1Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.
Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|June 2, 1998
Summary
Nitric oxide (NO) suppresses APO-1/Fas-induced apoptosis by inhibiting caspase activation. This NO-mediated resistance to cell death impacts immune responses and autoimmune diseases.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Caspase activation is essential for APO-1/Fas-induced apoptosis.
- Nitric oxide (NO) is a signaling molecule with diverse biological functions.
Purpose of the Study:
- To investigate the effect of nitric oxide (NO) on APO-1/Fas-mediated apoptosis.
- To elucidate the mechanism by which NO modulates caspase activation.
Main Methods:
- Jurkat cells were treated with exogenous NO donors or transfected with inducible NO synthase.
- APO-1/Fas-induced apoptosis, caspase activation, and caspase-3 cleavage were assessed.
- The effect of NO on caspase-8 and caspase-1 was examined through S-nitrosylation.
Main Results:
- Nitric oxide (NO) significantly suppressed APO-1/Fas-triggered cell death in Jurkat cells.
- NO inhibited the activation and proteolytic cleavage of caspase-3 (CPP32).
- NO interfered with apoptosis induction by FADD and caspase-8, and directly S-nitrosylated caspase-8 and caspase-1.
Conclusions:
- Nitric oxide (NO) modulates the caspase proteolytic cascade upstream of caspase-3.
- NO-induced resistance to apoptosis may be significant in immune responses and autoimmune pathogenesis.