Molecular mechanism of satratoxin-induced apoptosis in HL-60 cells: activation of caspase-8 and caspase-9 is involved in activation of caspase-3.

Abstract

Satratoxins have been recognized as potential immunomodulatory agents in outbreaks of building-related illness. Here we report that satratoxin G-treated human leukemia HL-60 cells underwent apoptosis through the action of caspase-3 which was activated by both caspase-8 and caspase-9. Western blot analysis of caspase-3 in the satratoxin G-treated cells apparently indicated the appearance of a catalytically active fragment of 17 kDa. Increased caspase-3 activity was also detected by using a fluorogenic substrate, DEVD-AMC. Next, exposure to satratoxin G led to cleavage of PARP from its native 116 kDa form to a 85 kDa product. Moreover, DFF-45/ICAD were cleaved into a 12.5 kDa fragment via satratoxin G treatment. Enzymic assay on IETD-AMC revealed that caspase-8 is strongly activated by exposure to satratoxin G while T-2 toxin (T-2) could not activate caspase-8 at an early stage of apoptosis. Furthermore, satratoxin G caused a release of cytochrome c from mitochondria into the cytosol and increased the activity of caspase-9 against LEHD-AMC. These findings indicate that satratoxin G-induced apoptosis involves activation of caspase-3 and DFF-40/CAD through both activation of caspase-8 and cytosolic accumulation of cytochrome c along with activation of caspase-9.

• Authors: Masahiro Nagase, Tetsuya Shiota, Akiko Tsushima, Mohammad Murshedul Alam, Satoshi Fukuoka, Takumi Yoshizawa, Nobuo Sakato
• Journal: Immunology letters (Immunol Lett) Vol. 84 Issue 1 Pg. 23-7 (Oct 21 2002) ISSN: 0165-2478 [Print] Netherlands
• PMID: 12161280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coumarins
• Cytochrome c Group
• Fluorescent Dyes
• Immunosuppressive Agents
• Oligopeptides
• Poly-ADP-Ribose Binding Proteins
• Trichothecenes
• acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin
• satratoxin G
• Poly(ADP-ribose) Polymerases
• DFFB protein, human
• Deoxyribonucleases
• CASP3 protein, human
• CASP8 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases

Topics

• Apoptosis (drug effects)
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases (metabolism)
• Coumarins
• Cytochrome c Group (metabolism)
• Deoxyribonucleases (metabolism)
• Enzyme Activation (drug effects)
• Fluorescent Dyes
• HL-60 Cells
• Humans
• Immunosuppressive Agents (toxicity)
• Oligopeptides
• Poly(ADP-ribose) Polymerases (metabolism)
• Poly-ADP-Ribose Binding Proteins
• Sick Building Syndrome (etiology)
• Stachybotrys (pathogenicity)
• Trichothecenes (toxicity)