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| Nitric oxide suppression of apoptosis occurs in association with an inhibition of Bcl-2 cleavage and cytochrome c release |
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| Author(s): Kim YM, Kim TH, Seol DW, Talanian RV, Billiar TR |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 273 Issue: 47 Pages: 31437-31441 Published: NOV 20 1998 |
| Times Cited: 161 References: 36 |
| Abstract: It is now known that caspase-3-like protease activation can promote BcI-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 alpha- 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Billiar, TR (reprint author), Presbyterian Univ Hosp, A1010,200 Lothrop St, Pittsburgh, PA 15213 USA |
Addresses:
1. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA
2. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA
3. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA
4. Kangwon Natl Univ, Coll Med, Dept Mol & Cellular Biochem, Chunchon 200701, South Korea
5. BASF Biores Corp, Worcester, MA 01605 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 141HG |
| ISSN: 0021-9258 |
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