Gliotoxin induces the Apoptosis in HL-60 Cells.
- Author:
Hun Taeg CHUNG
;
Rae Kil PARK
;
Yong Keel CHOI
;
Sang Rock LEE
;
Young Hee KIM
;
Kwang Ho CHO
;
Young Woo JANG
- Publication Type:Original Article
- Keywords:
Gliotoxin;
JNK1;
Caspase-3;
Transcription factors
- MeSH:
Apoptosis*;
Aspergillus;
Caspase 3;
Cysteine Proteases;
DNA;
Fungi;
Gliocladium;
Gliotoxin*;
HL-60 Cells*;
Humans;
Mitogen-Activated Protein Kinases;
NF-kappa B;
Penicillium;
Thermoascus;
Transcription Factor AP-1;
Transcription Factors
- From:Korean Journal of Immunology
1998;20(4):397-403
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Many fungi including Penicillium, Aspergillus, Gliocladium, and Thermoascus produce an epipolythiodioxopiperazine class of fungal metabolite, gliotoxin, which contirbutes the pathogenesis of fungal infection as an immunomodulator and cytotoxic agent. This study is designed to define the mechanism by which gliotoxin exerts the cytotoxic effect of gliotoxin on human promyelocytic leukemic cells, HL-60. Gliotoxin induces the apoptosis of HL-60 cells which is characterized by the ladder pattern fragmentation of DNA. Gliotoxin induces the activation of DEVD-specific cysteine protease in a time- and dose-dependent rnanner. It also increases the phosphotransferase activities of c-Jun N-terminal kinase1 (JNK1) and p38 in gliotoxin-treated HL-60 cells. Furthermore, gliotoxin decreases the activation of transcriptional activator, actiating protein (AP-1) and NF-kB. These results suggest that gliotoxin induces the apoptotic death of HL-60 cells via activation of DEVD- specific caspase as well as mitogen activated protein kinases (MAP kinases) including JNK1 and p38, and inhibition of transcriptional activators, AP-1 and NF-kB.
