Cadmium stimulates MAPKs and Hsp27 phosphorylation in bovine adrenal chromaffin cells

Cadmium (Cd2+) is a common environmental pollutant, which is widely used in industry and is a constituent of tobacco smoke. Exposure to this heavy metal has been linked to a wide range of detrimental effects on mammalian cells. In this study, the action of Cd2+ on protein phosphorylation in bovine adrenal chromaffin cells (BACCs) was examined. Cells were incubated with 32Pi in the presence of Cd2+ (1–50 μM) and proteins were separated by one- or two-dimensional electrophoresis. An increase in the phosphorylation of BACCs proteins, without changing cell viability, was observed in response to Cd2+ (5–50 μM). Particularly at three spots, with molecular weight of 25 kDa and isoeletric point range 4.0–4.5, which were identified as phosphorylated isoforms of the heat shock protein of 27 kDa (Hsp27). Phosphorylation of the p38MAPK, a member of mitogen-activated protein kinase (MAPK) family, was stimulated by Cd2+ over the same concentration range and it was the major upstream protein kinase involved in the phosphorylation of all three spots of Hsp27. Cd2+ also stimulated the phosphorylation of other MAPK family member, the extracellular signal-regulated kinase (ERK)-1/2. Therefore, primary adrenal chromaffin cells are a target for Cd2+ and both the ERK1/2 and the p38MAPK are activated. Additionally, Hsp27 is highly phosphorylated in response to the metal exposure, due to p38MAPK activation. These biochemical effects of Cd2+ might disrupt the normal secretory function of these cells.