Stimulation of calmodulin by cadmium ion.
Cd2+, a serious environmental pollutant in certain industrial regions, accumulates in mammalian tissues with a very slow turnover. Using various criteria, we studied the ability of Cd2+ to substitute for Ca2+ in calmodulin (CaM), a ubiquitous Ca2+-binding protein that mediates many of the Ca2+ effects. CaM bound Cd2+ with a Kd of 4.5 microM, presumably to the Ca2+-binding sites. Binding of Cd2+ allowed CaM to bind 2 moles chlorpromazine, or to form a complex with skeletal muscle troponin-I, troponin-T, or phosphodiesterase. Complex formation with phosphodiesterase led to its activation, which was observed even in the presence of glutathione or cysteine, agents known to chelate Cd2+. This raises the possibility that one manifestation of Cd2+ toxicity may be through its activation of CaM, thus upsetting its normal regulation by a cellular flux of Ca2+.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D002746:Chlorpromazine / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D011487:Protein Conformation / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014336:Troponin / Q000378:metabolism
D002147:Calmodulin; D013438:Sulfhydryl Compounds; D014336:Troponin; D002104:Cadmium; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D005978:Glutathione; D002746:Chlorpromazine