Abstract
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 ubiquitious Ca2+-binding protein that mediates many of the Ca2+ effects. CaM bound Cd2+ with a Kd of 4.5 μM, 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+.
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This work was supported by grants CA 21765, NS 08059 and GM 28178 from the NIH and by American Lebanese Syrian Associated Charities. J. R. Z. was a recipient of a National Research Service Award, CA 09346, USA
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Suzuki, Y., Chao, SH., Zysk, J.R. et al. Stimulation of calmodulin by cadmium ion. Arch Toxicol 57, 205–211 (1985). https://doi.org/10.1007/BF00290889
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DOI: https://doi.org/10.1007/BF00290889