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Zn2+-induced ERK activation mediated by reactive oxygen species causes cell death in differentiated PC12 cells

Authors
 Su Ryeon Seo  ;  Seon Ah Chong  ;  Syng‐Ill Lee  ;  Jee Young Sung  ;  Young Soo Ahn  ;  Kwang Chul Chung  ;  Jeong Taeg Seo 
Citation
 JOURNAL OF NEUROCHEMISTRY, Vol.78(3) : 600-610, 2001 
Journal Title
 JOURNAL OF NEUROCHEMISTRY 
ISSN
 0022-3042 
Issue Date
2001
MeSH
Animals ; Antifungal Agents/pharmacology ; Antioxidants/pharmacology ; Apoptosis/drug effects* ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Flavonoids/pharmacology ; Immunoblotting ; Indoles/pharmacology ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System/physiology ; Maleimides/pharmacology ; Microscopy, Fluorescence ; Mitogen-Activated Protein Kinases/metabolism* ; Neurons/cytology* ; Neurons/drug effects ; Neurons/metabolism PC12 Cells ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/metabolism ; Pyridines/pharmacology ; Rats ; Reactive Oxygen Species/metabolism* ; Thiones ; Time Factors ; Transfection ; Zinc/pharmacology* ; p38 Mitogen-Activated Protein Kinases ; ras Proteins/metabolism
Abstract
Recent studies have provided evidence that Zn2+ plays a crucial role in ischemia- and seizure-induced neuronal death. However, the intracellular signaling pathways involved in Zn2+-induced cell death are largely unknown. In the present study, we investigated the roles of mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK), and of reactive oxygen species (ROS) in Zn2+-induced cell death using differentiated PC12 cells. Intracellular accumulation of Zn2+ induced by the combined application of pyrithione (5 microM), a Zn2+ ionophore, and Zn2+ (10 microM) caused cell death and activated JNK and ERK, but not p38 MAPK. Preventing JNK activation by the expression of dominant negative SEK1 (SEKAL) did not attenuate Zn2+-induced cell death, whereas the inhibition of ERK with PD98059 and the expression of dominant negative Ras mutant (RasN17) significantly prevented cell death. Inhibition of protein kinase C (PKC) and phosphatidylinositol-3 kinase had little effect on Zn2+-induced ERK activation. Intracellular Zn2+ accumulation resulted in the generation of ROS, and antioxidants prevented both the ERK activation and the cell death induced by Zn2+. Therefore, we conclude that although Zn2+ activates JNK and ERK, only ERK contributes to Zn2+-induced cell death, and that ERK activation is mediated by ROS via the Ras/Raf/MEK/ERK signaling pathway.
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1471-4159.2001.00438.x
DOI
10.1046/j.1471-4159.2001.00438.x
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/164961
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