Mercury chloride activates c-Jun N-terminal kinase and induces c-jun expression in LLC-PK1 cells.
In response to various environmental stresses including heavy metals, the c-Jun N-terminal kinase (JNK) is phosphorylated and then it phosphorylates c-Jun protein. In the present study, effects of mercury chloride (HgCl2) on JNK signalling pathway were examined in LLC-PK1 cells. When exposed to 10 or 20 microM HgCl2, the level of phosphorylated JNK and the activity of JNK assayed in vitro using glutathione-S-transferase-c-Jun as substrate increased markedly. The level of phosphorylated JNK increased 30 min after HgCl2 exposure and remained elevated even at 8 h. On the other hand, no changes were found in the total amount of JNK protein. Consistent with the activation of JNK, c-Jun proteins phosphorylated on Ser63 and Ser73 were accumulated in cells exposed to HgCl2. Concomitantly, the levels of c-jun mRNA and c-Jun protein were elevated. When compared to other heavy metal compounds such as manganese chloride, zinc chloride, cadmium chloride, and lead chloride, HgCl2 could phosphorylate JNK more markedly. Neither intracellular Ca2+ nor sulfhydryl groups appeared to play a major role in the activation of JNK by HgCl2 exposure in this porcine renal epithelial cell line.
Matsuoka
M
M
Department of Environmental Toxicology, University of Occupational and Environmental Health, Kitakyushu, Japan. masatomm@med.uoeh-u.ac.jp
Wispriyono
B
B
Iryo
Y
Y
Igisu
H
H
D000818:Animals; D015153:Blotting, Western; D019256:Cadmium Chloride / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005033:Ethylmaleimide / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D018374:LLC-PK1 Cells / Q000201:enzymology*; D008627:Mercuric Chloride / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D008627:Mercuric Chloride; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D019256:Cadmium Chloride; D005033:Ethylmaleimide