Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Gliotoxin-Induced Oxidative Stress Mediates the Apoptotic Death in Human Leukemic HL-60 cells

진균독소 Gliotoxin-유도성 산화적 손상에 의한 Apoptosis

  • 장해란 (원광대학교 의과대학 미생물학교실) ;
  • 김영희 (원광대학교 의과대학 미생물학교실) ;
  • 김남송 (원광대학교 의과대학 미생물학교실 및 예방의학교실) ;
  • 원진숙 (전북대학교 의과대학 생화학교실) ;
  • 조정환 (원광대학교 의과대학 미생물학교실) ;
  • 윤재도 (원광대학교 의과대학 미생물학교실) ;
  • 임창인 (원광대학교 의과대학 미생물학교실) ;
  • 김호찬 (원광대학교 의과대학 미생물학교실) ;
  • 최익준 (원광대학교 의과대학 미생물학교실)
  • Published : 2002.09.01
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Abstract

Fungal metabolite, gliotoxin is an epipolythiodioxopiperazin (ETP) class and has various roles including immunomodulatory and apoptotic effects. This study was designed to evaluate the mechanism by which gliotoxin exerts the apoptosis on human promyelocytic leukemic HL-60 cells. Herein, we demonstrated that the gliotoxin decreased the cell viability in a time-dependent manner Gliotoxin-induced cell death was confirmed us apoptosis characterized by chromatin condensation and ladder-pattern fragmentation of genomic DNA. Gliotoxin increased the catalytic activities of caspase-3 and caspase-9. Activation of caspase-3 was further confirmed by degradation of procaspase-3 and poly(ADP-ribose) polymerase (PARP) by gliotoxin in HL-60 cells. Furthermore, gliotoxin induced the changes of mitochondrial transmembrane potential (MTP). Antioxidants, including GSH and NAC, markedly inhibited apoptosis with conistent suppression of enzymatic activity of caspase-3, caspase-9, and MTP loss in gliotoxin-treated cells. Taken together, we suggest that gliotoxin function as an oxidant and ploys proapoptotic roles in HL-60 cells via activation of intrinsic caspase cascades as well as mitochondrial dysfunction.

Keywords

References

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