Document Detail


p38 and ERK, but not JNK, are involved in copper-induced apoptosis in cultured cerebellar granule neurons.
MedLine Citation:
PMID:  19138669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Copper (Cu(2+)) is an essential element for a variety of cellular functions; however, it is involved in neurotoxic events at excessive doses. Mechanisms of Cu(2+)-induced neurotoxicity are not well understood. Here, we studied the toxic effects of Cu(2+) on cultured cerebellar granule neurons (cCGNs). Treatment of cCGNs with CuCl(2) (50 and 75muM) caused a concentration- and time-dependent cell death with apoptotic characters, including chromatin condensation and DNA ladder. Cu(2+) potently induced reactive oxygen species (ROS), and quickly and slightly increased the intracellular concentration of calcium. Western blot assay showed that Cu(2+) increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and ERK1/2, but not that of JNK-1. Pharmacological inhibition of calcium influx, p38 MAPK and ERK1/2 attenuated the Cu(2+) toxicity in cCGNs. These findings demonstrate that p38 MAPK and ERK1/2, but not JNK, are involved in apoptosis of cCGNs induced by copper, and p38 and ERK may be the downstream effectors of ROS and calcium signaling.
Authors:
Xiaohong Chen; Xiujian Lan; Suilin Mo; Jian Qin; Wenming Li; Peiqing Liu; Yifan Han; Rongbiao Pi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-10
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  379     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-03-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  944-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Calcium / metabolism
Cells, Cultured
Cerebellum / cytology,  drug effects*,  enzymology
Copper / toxicity*
JNK Mitogen-Activated Protein Kinases / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Mitogen-Activated Protein Kinases / metabolism*
Neurons / drug effects,  enzymology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 7440-50-8/Copper; 7440-70-2/Calcium; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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