MAPK activation is involved in cadmium-induced Hsp70 expression in HepG2 cells.

Cadmium is one of the most toxic elements to which man can be exposed at work or in the environment. By far, the most salient toxicological property of Cd is its exceptionally long half-life in the human body. Once absorbed, Cd accumulates in the human body, particularly in the liver and other vital organs. The cellular actions of Cd are extensively documented, but the molecular mechanisms underlying these actions are still not resolved. It is known that Cd activates the activator protein-1 (AP-1), but no data about the pathway involved are reported for liver. The objective was to provide a greater insight into the effect of cadmium on mitogen-activated protein kinases (MAPK's) involved in signal transduction, its relationship with AP-1 activation, and heat shock protein (Hsp) 70 expression, in HepG2 cells. AP-1 activation as a result of 5 microM CdCl(2) exposure was increased 24.5-fold over control cells after 4 h treatment. To investigate the role of the extracellular signal-regulated protein kinases (ERK's), c-Jun N-terminal kinases (JNK's) and p38 kinases in cadmium-induced AP-1 activation, specific MAPKs inhibitors were used. AP-1 activation decreased by 74% with ERK inhibition, by 83% with p38 inhibition, while inhibition of JNK decreased by 70%. Only ERK and JNK participated in Hsp70 production, conferring cell protection against cadmium damage.