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 μM 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.