Document Detail

Biphasic effect of cadmium on cell proliferation in human embryo lung fibroblast cells and its molecular mechanism.
MedLine Citation:
PMID:  19573589     Owner:  NLM     Status:  MEDLINE    
Hormesis, a biphasic dose-response phenomenon, is characterized by a low-dose stimulation and a high-dose inhibition. However, the mechanisms underlying hormesis induced by environmental agents are not well elucidated. The present study was to investigate the relationship between the hormesis effect of cadmium (Cd) and activation of ERK1/2, JNK and p38 pathways in human embryo lung fibroblast cells. Results showed that Cd induced significant cell proliferation at low concentrations, but markedly inhibited cell growth at high concentrations. Our data indicated that cell proliferation promoted by low concentrations of Cd was blocked obviously by ERK1/2 inhibitor PD98059 and partly by JNK inhibitor SP600125; while the decreases of cell proliferation induced by high concentrations of Cd were significantly restored by p38 inhibitor SB203580. Further analysis showed that phospho-ERK1/2 and phospho-JNK activities were increased with different concentrations of Cd, whereas phospho-p38 activity was markedly increased at high concentrations. Our findings suggested that low concentration of Cd induces the ERK and JNK pathways and promotes cell proliferation; while high concentration of Cd induces p38 pathway and inhibits cell proliferation. Activation of the ERK1/2 pathways seems to play a more important role than the JNK pathway in the biphasic effect of Cd on cell proliferation.
Gaofeng Jiang; Weixia Duan; Lei Xu; Shizhen Song; Changcai Zhu; Lei Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-30
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  23     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-11-30     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  973-8     Citation Subset:  IM    
Faculty of Preventive Medicine, Medical College, Wuhan University of Science and Technology, Wuhan 430065, People's Republic of China.
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MeSH Terms
Anthracenes / pharmacology
Cadmium / administration & dosage,  toxicity*
Cell Line
Cell Proliferation / drug effects*
Dose-Response Relationship, Drug
Fibroblasts / drug effects*,  metabolism
Flavonoids / pharmacology
Imidazoles / pharmacology
JNK Mitogen-Activated Protein Kinases / metabolism
Lung / cytology,  drug effects,  metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Pyridines / pharmacology
p38 Mitogen-Activated Protein Kinases / metabolism
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Anthracenes; 0/Flavonoids; 0/Imidazoles; 0/Pyridines; 0/SB 203580; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 7440-43-9/Cadmium; EC Mitogen-Activated Protein Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Mitogen-Activated Protein Kinases

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