Modulation of stress proteins by Cd2+ in a human T cell line.
We previously showed in a human T cell line (CEM-C12 cells) that Cd2+ induced gene expression of stress proteins, metallothionein-IIA and heat shock protein 70 in a time- and dose-dependent manner. In the present study, CEM-C12 cells were pretreated for 24 h with 1 microM Cd2+ and then challenged with toxic concentrations of this metal. We found that maximal expression of the metallothionein-IIA and heat shock protein 70 genes was increased and this maximal level occurred at higher Cd2+ toxic concentrations. Actinomycin D chase experiments indicated that Cd2+ pretreatment did not modify metallothionein-IIA mRNA stability. The modulatory effect of Cd2+ pretreatment was dose-dependent from 100 pM to 1 microM. Such pretreatment also enhanced resistance to Cd2+ toxicity. Finally, verapamil, a calcium/potassium channel blocker displaced the dose-response curve for Cd2+ toxicity as well as metallothionein-IIA and heat shock protein 70 gene expression to higher Cd2+ concentrations.
Institut National de la Santé et de la Recherche Médicale (INSERM) U 200, Clamart, France.
O
O
Pellegrini
E
E
Davenas
L
L
Morin
G T
GT
Tsangaris
J
J
Benveniste
Y
Y
Manuel
Y
Y
Thomas
D015152:Blotting, Northern; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015342:DNA Probes; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D014700:Verapamil / Q000494:pharmacology
D015342:DNA Probes; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein; D014700:Verapamil