The Journal of the Korean Society for Microbiology (대한미생물학회지)

The Korea Society for Microbiology (대한미생물학회)
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The Protective Mechanism of Zinc in Fungal Metabolite Gliotoxin-induced Apoptosis

진균독소 Gliotoxin에 의한 세포고사에서 Zinc의 예방적 역할

  • Park, Ji-Sun (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • So, Hong-Seob (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Kim, Myung-Sunny (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Jung, Byung-Hak (Department of Hematology/Oncology, School of Medicine, Wonkwang University) ;
  • Choi, Ik-Jun (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Jin, Gyung-Ho (Department of Preventive Medicine, School of Medicine, Wonkwang University) ;
  • Jin, Sung-Ho (Department of Preventive Medicine, School of Medicine, Wonkwang University) ;
  • Kim, Nam-Song (Department of Preventive Medicine, School of Medicine, Wonkwang University) ;
  • Cho, Kwang-Ho (Department of Neurology School of Medicine, Wonkwang University) ;
  • Park, Rae-Kil (Department of Microbiology, School of Medicine, Wonkwang University)
  • 박지선 (원광대학교 의과대학 미생물학교실) ;
  • 소홍섭 (원광대학교 의과대학 미생물학교실) ;
  • 김명선 (원광대학교 의과대학 미생물학교실) ;
  • 정병학 (원광대학교 의과대학 혈액종양내과) ;
  • 최익준 (원광대학교 의과대학 미생물학교실) ;
  • 진경호 (원광대학교 의과대학 예방의학교실) ;
  • 진성호 (원광대학교 의과대학 예방의학교실) ;
  • 김남송 (원광대학교 의과대학 예방의학교실) ;
  • 조광호 (원광대학교 의과대학 신경과학교실) ;
  • 박래길 (원광대학교 의과대학 미생물학교실)
  • Published : 1999.12.31
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Abstract

Gliotoxin, a fungal metabolite, is one of the epipolythiodioxopiperazine classes and has a variety of effects including immunomodulatory and apoptotic agents. This study is designed to evaluate the effect of zinc on gliotoxin-induced death of HL-60 cells. Here, we demonstrated that treatment of gliotoxin decreased cell viability in a dose and time-dependent manner. Gliotoxin-induced cell death was confirmed as apoptosis characterized by chromatin margination, fragmentation and ladder-pattern digestion of genomic DNA. Gliotoxin increased the proteolytic activities of caspase 3, 6, 8, and 9. Caspase-3 activation was further confirmed by the degradation of procaspase-3 and PARP in gliotoxin-treated HL-60 cells. Zinc compounds including $ZnCl_2$ and $ZnSO_4$ markedly inhibited gliotoxin-induced apoptosis in HL-60 cells (from 30% to 90%). Consistent with anti-apoptotic effects, zinc also suppressed the enzymatic activities of caspase-3 and -9 proteases. In addition, cleavage of both PARP and procaspase 3 in gliotoxin-treated HL-60 cells was inhibited by the addition of zinc compounds. We further demonstrated that expression of Fas ligand by gliotoxin was suppressed by zinc compounds. These data suggest that zinc may prevent gliotoxin-induced apoptosis via inhibition of Fas ligand expression as well as suppression of caspase family cysteine proteases-3 and -9 in HL-60 cells.

Keywords

References

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