| p38 and ERK, but not JNK, are involved in copper-induced apoptosis in cultured cerebellar granule neurons. | |
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MedLine Citation:
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PMID: 19138669 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiaohong Chen; Xiujian Lan; Suilin Mo; Jian Qin; Wenming Li; Peiqing Liu; Yifan Han; Rongbiao Pi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-10 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 379 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-06 Completed Date: 2009-03-16 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 944-8 Citation Subset: IM |
Affiliation:
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Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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