Activation of c-Jun NH2-terminal kinase (JNK/SAPK) in LLC-PK1 cells by cadmium.
The level of phosphorylated c-Jun NH2-terminal kinase (JNK) in LLC-PK1 cells treated with CdCl2 increased after 30 min and remained elevated even at 8 hr. And the activity of JNK assayed using glutathione S-transferase-c-Jun as substrate increased dose-dependently. Consistent with the JNK activation, marked increases in the levels of c-Jun and c-Jun phosphorylated on Ser63 and Ser73 were observed in cells treated with CdCl2. The pretreatment with an intracellular Ca2+ chelator, 1, 2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA/AM), abolished cadmium-induced JNK phosphorylation. However, pretreatment with a cell permeable chelator of heavy metals, N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), did not. The present results showed that cadmium induces persistent activation of JNK pathway in a renal epithelial cell line, and that intracellular Ca2+ is necessary for the activation.
Matsuoka
M
M
Department of Environmental Toxicology, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan. masatommmed.uoeh-u.ac.jp
Igisu
H
H
D000818:Animals; D019256:Cadmium Chloride / Q000493:pharmacokinetics / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D018374:LLC-PK1 Cells; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine; D013552:Swine
D002614:Chelating Agents; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D012694:Serine; D004533:Egtazic Acid; D005982:Glutathione Transferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019256:Cadmium Chloride