PMID- 14977522
OWN - NLM
STAT- MEDLINE
DCOM- 20040415
LR  - 20131121
IS  - 0271-3683 (Print)
IS  - 0271-3683 (Linking)
VI  - 28
IP  - 3
DP  - 2004 Mar
TI  - Zn2+-induced cell death is mediated by the induction of intracellular ROS in 
      ARPE-19 cells.
PG  - 195-201
AB  - 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.
FAU - Song, Jeongmin
AU  - Song J
AD  - Department of Ophthalmology, Institute of Vision Research, Yonsei University 
      College of Medicine, Seoul, Korea.
FAU - Lee, Sung Chul
AU  - Lee SC
FAU - Kim, Sung Soo
AU  - Kim SS
FAU - Koh, Hyung J
AU  - Koh HJ
FAU - Kwon, Oh Woong
AU  - Kwon OW
FAU - Kang, Jimmy Jaeyoung
AU  - Kang JJ
FAU - Kim, Eung Kweon
AU  - Kim EK
FAU - Shin, Seung-Hun
AU  - Shin SH
FAU - Lee, Joon H
AU  - Lee JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Chlorides)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Zinc Compounds)
RN  - 86Q357L16B (zinc chloride)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Survival
MH  - Chlorides/*pharmacology
MH  - Fluorescein-5-isothiocyanate
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - MAP Kinase Kinase 4
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Necrosis
MH  - Pigment Epithelium of Eye/metabolism/*pathology
MH  - Reactive Oxygen Species/antagonists & inhibitors/*metabolism
MH  - Zinc Compounds/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2004/02/24 05:00
MHDA- 2004/04/16 05:00
CRDT- 2004/02/24 05:00
PHST- 2004/02/24 05:00 [pubmed]
PHST- 2004/04/16 05:00 [medline]
PHST- 2004/02/24 05:00 [entrez]
AID - 10.1076/ceyr.28.3.195.26251 [doi]
PST - ppublish
SO  - Curr Eye Res. 2004 Mar;28(3):195-201. doi: 10.1076/ceyr.28.3.195.26251.