Activation of troponin C by Cd2+ and Pb2+.
Certain heavy metal actions such as Cd2+ and Pb2+ mimic Ca2+ effectively in stimulating calmodulin (CaM). We now show that these cations also activate skeletal muscle troponin C (TnC), a Ca2(+)-binding protein highly homologous to CaM. Like Ca2+, these cations allow TnC to alter its electrophoretic mobility on polyacrylamide gels, and to bind to phenyl-Sepharose. Moreover, they activate TnC to stimulate myofibrillar ATPase. When TnC was removed from the skeletal myofibrils by treatment with trans-1,2-cyclohexanediamine-N,N,N',N'-tetraacetic acid (CDTA), the ATPase activity was no longer stimulated by the cations. However, after reconstitution of CDTA-treated skeletal myofibril with TnC, the response of ATPase to Ca2+, Cd2+ or Pb2+ was restored. These findings suggest that the activation of myofibrillar ATPase by Cd2+ and Pb2+ is mediated through TnC. The ability of the heavy metals to stimulate TnC-supported ATPase activity correlated quite well with the ability to increase the extent of the myofibrillar superprecipitation. The activation of TnC by Cd2+ or Pb2+ could constitute a possible molecular basis for their toxicity.
Chao
S H
SH
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38101.
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C H
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Cheung
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WY
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007854:Lead / Q000494:pharmacology*; D008670:Metals / Q000302:isolation & purification; D009124:Muscle Proteins / Q000032:analysis / Q000302:isolation & purification; D009210:Myofibrils / Q000201:enzymology; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D014336:Troponin / Q000378:metabolism*; D019209:Troponin C
D002147:Calmodulin; D008670:Metals; D009124:Muscle Proteins; D014336:Troponin; D019209:Troponin C; D002104:Cadmium; D007854:Lead; D000251:Adenosine Triphosphatases; D002118:Calcium