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Anti-apoptotic Activity of Heme Oxygenase-1 Up-regulated by Etoposide in Human Retinal Pigment Epithelial Cells

Etoposide에 의한 인간 망막색소상피세포인 ARPE-19 세포의 아폽토시스 과정에서 Heme oxygenase-1의 항아폽토시스 기능에 대한 연구

  • Lee, Sang-Kwon (Department of Cardiovascular Surgery and Medical Research Institute, Pusan National University School of Medicine) ;
  • Song, Ju-Dong (Department of Microbiology & Immunology, Pusan National University School of Medicine) ;
  • Kim, Kang-Mi (Department of Microbiology & Immunology, Pusan National University School of Medicine) ;
  • Kim, Jong-Min (Department of Anatomy and Cell Biology, Dong-A University School of Medicine) ;
  • Lee, Sang-Yull (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Yoo, Young-Hyun (Department of Anatomy and Cell Biology, Dong-A University School of Medicine) ;
  • Park, Young-Chul (Department of Microbiology & Immunology, Pusan National University School of Medicine)
  • 이상권 (부산대학교 의학전문대학원 흉부외과학교실 및 의학연구소) ;
  • 송주동 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 김강미 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 김종민 (동아대학교 의과대학 해부학교실) ;
  • 이상률 (부산대학교 의학전문대학원 생화학교실) ;
  • 유영현 (동아대학교 의과대학 해부학교실) ;
  • 박영철 (부산대학교 의학전문대학원 미생물학 및 면역학교실)
  • Published : 2007.09.30

Abstract

The topoisomerase II inhibitor etoposide causes an accumulation of DNA double strand breaks within the nuclei of cells. In this study, we investigated the effect of etoposide on the cell growth and apoptosis of human RPE cells. Etoposide evoked a significant inhibition of cell growth, and also induced DNA fragmentation in ARPE-19 cells. In addition, etoposide significantly up-regulated the expression of heme oxygenase-1 (HO-1), which is a stress-responsive protein and is known to play a protective role against the oxidative injury. And, etoposide-induced HO-1 expression was affected by the ROS scavenger N-acetyl cysteine. We also used oligonucleotides interfering with HO-1 mRNA (siRNA) for the inhibition of HO-1 expression. Interestingly, knock-down of the HO-1 gene significantly increased the level of DNA fragmentation in etoposide-treated ARPE-19 cells. In conclusion, these results suggest that up-regulated HO-1 plays as an anti-apoptotic factor in the process of apoptosis of ARPE-19 cells stimulated by etoposide.

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