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Zn2+ -induced cell death is mediated by the induction of intracellular ROS in ARPE-19 cells

 Jeongmin Song  ;  Sung Chul Lee  ;  Joon H. Lee  ;  Seung-Hun Shin  ;  Eung Kweon Kim  ;  Jimmy Jaeyoung Kang  ;  Oh Woong Kwon  ;  Hyung J. Koh  ;  Sung Soo Kim 
 Current Eye Research, Vol.28(3) : 195-201, 2004 
Journal Title
 Current Eye Research 
Issue Date
apoptosis ; mitogen-activated protein kinases ; necrosis ; reactive oxygen species ; Zn2+
PURPOSE: Recent studies have shown that Zn2+ induced cell death in retinal pigment epithelial cells. Here we sought to investigate the mode of Zn2+-induced cell death and the role of reactive oxygen species (ROS) in human retinal pigment epithelial cell line, ARPE-19 cells. METHODS: Cell viability was measured by MTT assay. Cell death of ARPE-19 cells was measured by annexin V-fluorescein isothiocyanate (FITC) binding assay, TUNEL assay. The formation of intracellular ROS was measured using 2',7'-dichlorofluorescein diacetate (DCFH-DA). The activation of mitogen-activated protein kinase (MAPK) was examined by Western blot analysis. RESULTS: This study demonstrated that Zn2+ treatment induced both necrosis and apoptosis in ARPE-19 cells. Exposure of ARPE-19 cells to Zn2+ led to the activation of ERK1/2, JNK1/2/3, and p38 MAPKs. The activation of these MAPKs was blocked by treatment with the antioxidant, N-acetylcystein (NAC). More importantly, inhibition of ROS production by NAC completely prevented Zn2+-induced cell death in RPE cells. CONCLUSIONS: This study suggests that Zn2+ induces both apoptosis and necrosis in ARPE-19 cells and that its cytotoxicity may depend on the induction of intracellular ROS.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Koh, Hyoung Jun(고형준) ORCID logo https://orcid.org/0000-0002-5932-8516
Kwon, Oh Woong(권오웅)
Kim, Sung Soo(김성수) ORCID logo https://orcid.org/0000-0002-0574-7993
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Lee, Sung Chul(이성철) ORCID logo https://orcid.org/0000-0001-9438-2385
Lee, Joon Haeng(이준행)
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