Biphasic effect of cadmium on cell proliferation in human embryo lung fibroblast cells and its molecular mechanism.
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.
Jiang
Gaofeng
G
Faculty of Preventive Medicine, Medical College, Wuhan University of Science and Technology, Wuhan 430065, People's Republic of China. jianggaofeng@yahoo.com.cn
Duan
Weixia
W
Xu
Lei
L
Song
Shizhen
S
Zhu
Changcai
C
Wu
Lei
L
D000873:Anthracenes / Q000494:pharmacology; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D002104:Cadmium; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one