title: Low dose cadmium poisoning results in sustained ERK phosphorylation and caspase activation.
abstract: Cadmium poisoning has been known to result in a wide variety of cellular responses, including oxidative stress and kinase activation. It has been reported that ERK is activated following acute cadmium exposure, and this response is commonly seen as a classical ERK survival mechanism. Here, we analyzed different cell types for their responses to low concentrations of cadmium poisoning. We found that there is an association between cell susceptibility to cadmium toxicity and ERK activation. This activation is atypical, since it consists of a sustained ERK phosphorylation, that lasts up to 6 days post stimulation. This activation is associated with the appearance of cleaved caspases 8 and 3, processed PARP, and irreversible damage. Pharmacological inhibition of ERK phosphorylation results in the ability of cells to resist cadmium poisoning. Our data indicate that low cadmium concentrations result in an unconventional ERK sustained phosphorylation, which in turn leads to death signaling.
authors.affiliation: Transcriptional Regulation and Differentiation, CNRS UMR 6548, Nice University, Parc Valrose, 06108 Nice cedex 2, France. pmartin@unice.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Martin
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Poggi
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Chambard
authors.forename: Kim E
authors.initials: KE
authors.lastname: Boulukos
authors.forename: Philippe
authors.initials: P
authors.lastname: Pognonec
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002105:Cadmium Poisoning / Q000201:enzymology* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases