Cadmium stimulates MAPKs and Hsp27 phosphorylation in bovine adrenal chromaffin cells.
Cadmium (Cd(2+)) 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 Cd(2+) on protein phosphorylation in bovine adrenal chromaffin cells (BACCs) was examined. Cells were incubated with (32)Pi in the presence of Cd(2+) (1-50 microM) 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 Cd(2+) (5-50 microM). Particularly at three spots, with molecular weight of 25kDa and isoeletric point range 4.0-4.5, which were identified as phosphorylated isoforms of the heat shock protein of 27kDa (Hsp27). Phosphorylation of the p38(MAPK), a member of mitogen-activated protein kinase (MAPK) family, was stimulated by Cd(2+) over the same concentration range and it was the major upstream protein kinase involved in the phosphorylation of all three spots of Hsp27. Cd(2+) 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 Cd(2+) and both the ERK1/2 and the p38(MAPK) are activated. Additionally, Hsp27 is highly phosphorylated in response to the metal exposure, due to p38(MAPK) activation. These biochemical effects of Cd(2+) might disrupt the normal secretory function of these cells.
Leal
Rodrigo B
RB
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. bainyle@mbox1.ufsc.br
Posser
Thaís
T
Rigon
Ana Paula
AP
Oliveira
Camila S
CS
Gonçalves
Carlos Alberto
CA
Gelain
Daniel P
DP
Dunkley
Peter R
PR
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D010759:Phosphorus Isotopes; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007093:Imidazoles; D010759:Phosphorus Isotopes; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; D019256:Cadmium Chloride; C093642:SB 203580