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) |