Abstract
We have discovered that nitric oxide (NO), generated either by NO donors or produced intracellularly by the expression of the inducible nitric oxide synthase, suppresses hepatocyte apoptosis induced by TNFα, FasL or growth factor withdrawal. Caspase-3-like activity was found to be inhibited under these conditions. To investigate the interaction between NO and caspases, we utilized purified human recombinant caspases and examined the effect of NO on enzymatic activities of several caspase enzymes. Of the seven caspases studied (caspase-1, -2, -3, -4, -6, -7 and -8), all were reversibly inhibited by donors which release NO, OONO- or NO+. Dithiothreitol reversed the NO inhibition, supporting direct S-nitrosylation of the caspase catalytic cysteine residue by NO as the mechanism. Our results provide further support for the concept that NO is an endogenous regulator of caspase activity.
Original language | English |
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Pages (from-to) | A795 |
Journal | FASEB Journal |
Volume | 12 |
Issue number | 5 |
State | Published - 20 Mar 1998 |