RRC ID 41643
Author Nagase M, Shiota T, Tsushima A, Murshedul Alam M, Fukuoka S, Yoshizawa T, Sakato N.
Title Molecular mechanism of satratoxin-induced apoptosis in HL-60 cells: activation of caspase-8 and caspase-9 is involved in activation of caspase-3.
Journal Immunol Lett
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.
Volume 84(1)
Pages 23-7
Published 2002-10-21
DOI 10.1016/s0165-2478(02)00127-x
PII S016524780200127X
PMID 12161280
MeSH 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*
IF 3.276
Times Cited 25
WOS Category IMMUNOLOGY
Resource
Human and Animal Cells HL60(RCB001)