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

Jeongmin Song, Sungchul Lee, Sung Soo Kim, Hyung J. Koh, Oh Woong Kwon, Jimmy Jaeyoung Kang, Eungkweon Kim, Seung Hun Shin, Joon H. Lee

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Abstract

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.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalCurrent Eye Research
Volume28
Issue number3
DOIs
Publication statusPublished - 2004 Mar 1

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Song, J., Lee, S., Kim, S. S., Koh, H. J., Kwon, O. W., Kang, J. J., Kim, E., Shin, S. H., & Lee, J. H. (2004). Zn2+-induced cell death is mediated by the induction of intracellular ROS in ARPE-19 cells. Current Eye Research, 28(3), 195-201. https://doi.org/10.1076/ceyr.28.3.195.26251