| Lead stimulates ERK1/2 and p38MAPK phosphorylation in the hippocampus of immature rats. | |
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MedLine Citation:
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PMID: 14725969 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lead (Pb(2+)) is widely recognized as a neurotoxicant whose mechanisms of action are not completely established. We have previously demonstrated that Pb(2+) can activate the p38(MAPK) pathway and increase the phosphorylation of Hsp27 in bovine adrenal chromaffin cells and human SH SY5Y cells over a short incubation period (1 h). In the present work we analyzed the effects of Pb(2+) administered in vivo on the level and the phosphorylation state of ERK1/2 and p38(MAPK) in the hippocampus of immature rats. Rats were treated with lead acetate (2, 8 or 12 mg/kg, i.p.) or saline (control) over the 8th to 12th postnatal days, and hippocampal slices were prepared on the 14th day. The Pb(2+) level in the lead-treated animals increased 2.5-6-fold in the blood (3.0-6.0 microg/dl) and 2.0-3.0-fold in the forebrain (78-103 ng/g wet weight), compared to control (saline). The phosphorylation of both ERK1/2 and p38(MAPK) was significantly increased by prior exposure to Pb(2+) in vivo. In in vitro experiments, hippocampal slices from 14-day-old rats were exposed to Pb(2+) (1-10 microM) for 1 and 3 h. There were no changes in the phosphorylation state of ERK and p38(MAPK) for 1-h incubation, whereas a significant increase of ERK1/2 and p38(MAPK) phosphorylation by Pb(2+) (5 microM) was observed for the 3-h incubation. Cell viability measured using MTT was not modified in any of the conditions tested. These results indicate that the phosphorylation of hippocampal ERK1/2 and p38(MAPK) is stimulated by lead in a period of rapid brain development, an effect that may underlie, at least in part, the neurotoxicty elicited by this metal. |
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Authors:
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Fabiano M Cordova; Ana Lúcia S Rodrigues; Maria B O Giacomelli; Camila S Oliveira; Thaís Posser; Peter R Dunkley; Rodrigo B Leal |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brain research Volume: 998 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-01-16 Completed Date: 2004-03-22 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 65-72 Citation Subset: IM |
Affiliation:
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Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, SC, 88040-900, Florianópolis, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Animals, Newborn Blotting, Western Cell Survival / drug effects Female Hippocampus / drug effects*, metabolism Lead / metabolism, toxicity* Male Maximum Tolerated Dose Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases / metabolism* Phosphorylation / drug effects Prosencephalon / drug effects, metabolism Rats Rats, Wistar Time Factors p38 Mitogen-Activated Protein Kinases |
| Chemical | |
Reg. No./Substance:
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7439-92-1/Lead; 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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