Nitric oxide suppression of apoptosis occurs in association with an inhibition of Bcl-2 cleavage and cytochrome c release

Young Myeong Kim, Tae Hyoung Kim, Dai Wu Seol, Robert V. Talanian, Timothy R. Billiar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

217 Scopus citations

Abstract

It is now known that caspase-3-like protease activation can promote Bcl- 2 cleavage and mitochondrial cytochrome c release and that these events can lead to further downstream caspase activation. NO has been proposed as a potent, endogenous inhibitor of caspase-3-like protease activity. Experiments were carried out to determine whether NO could interrupt Bcl-2 cleavage or cytochrome c release by the inhibition of caspase activity linking these events. NO inhibited the capacity of purified caspase-3 to cleave recombinant Bcl-2. Both Bcl-2 cleavage and cytochrome c release were inhibited in tumor necrosis factor α- and actinomycin D-treated MCF-7 cells exposed to NO donors. The NO-mediated inhibition of Bcl-2 cleavage and cytochrome c release occurred in association with an inhibition of apoptosis and caspase-3-like activation. Thus, NO suppresses a key step in the positive feedback amplification of apoptotic signaling by preventing Bcl-2 cleavage and cytochrome c release.

Original languageEnglish
Pages (from-to)31437-31441
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number47
DOIs
StatePublished - 20 Nov 1998
Externally publishedYes

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