Abstract
In the search for the mode of action of aluminum ions in dialysis encephalopathy, their interaction with calmodulin has been assessed, and compared with those of Ca2+, Pb2+, Mn2+, Hg2+ and Cd2+. The basal and calmodulin-dependent activity of phosphodiesterase was measured in the presence of the ions, and their binding to calmodulin was assessed by competition with 45Ca2+ in flow dialysis. Al3+, Mn2+, Hg2+, and Cd2+ cannot be regarded as exclusive calmodulin antagonists or agonists, but rather interact with the phosphodiesterase itself. Pb2+ however, mimicks Ca2+ in every system tested, and is active in the same concentration range as Ca2+. Our results indicate that the assumed role of Al3+ ions in dialysis encephalopathy or other neurological disturbances is not linked with calmodulin.
Similar content being viewed by others
Abbreviations
- EGTA:
-
Ethyleneglycol-bis-(β-aminoethyl ether)
- N,N,N′,N′:
-
tetraacetic acid
References
Alfrey AC (1984) Aluminium intoxication. N Engl J Med 310: 1113–1114
Alfrey AC, LeGendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med 294: 184–188
Andreoli SP, Bergstein JM, Sherrard DJ (1984) Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 310: 1079–1084
Butcher RW, Sutherland EW (1962) Adenosine 3′,5′-phosphate in biological material. I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′5′-phosphate in human urine. J Biol Chem 237: 1244–1250
Chao SH, Suzuki Y, Zysk JR, Cheung WY (1984) Activation of calmodulin by various metal cations as a function of ionic radius. Mol Pharmacol 26: 75–82
Chen PS, Toribara TY, Warner H (1956) Microdetermination of phosphorus. Anal Chem 28: 1750–1758
Cheung WY (1969) Cyclic 3′5′-nucleotide phosphodiesterase: Preparation of a partially inactive enzyme and its subsequent stimulation by snake venom. Biochim Biophys Acta 191: 303–315
Colowick SP, Womack FC (1969) Binding of diffusible molecules by macromolecules: rapid measurement by rate of dialysis. J Biol Chem 244: 774–777
Feldmann K (1978) New devices for flow dialysis and ultrafiltration for the study of protein-ligand interactions. Anal Biochem 88: 225–235
Fiske CH, SubbaRow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66: 375–400
Goldstein GW, Ar D (1983) Lead activates calmodulin sensitive processes. Life Sci 33: 1001–1006
Habermann E, Crowell K, Janicki P (1983) Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol 54: 61–70
Howard JMH (1984) Clinical importance of small increases in serum aluminum. Clin Chem 30: 1722–1723
Klee CB, Krinks MH (1978) Purification of cyclic 3′,5′-nucleotide phosphodiesterase inhibitory protein by affinity chromatography on activator protein coupled to sepharose. Biochemistry 126: 203–207
Klee CB, Vanaman TC (1982) Calmodulin. Adv Protein Chem 35: 213–321
Lin YM, Liu YP, Cheung WY (1974) Cyclic 3′∶5′-nucleotide phosphodiesterase. J Biol Chem 249: 4943–4954
Lowry OH, Rosebrough NJ, Farr AL, Randall RF (1951) Protein measurement with the folin-phenol-reagent. J Biol Chem 193: 265–275
Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83: 346–356
Siegel N, Haug A (1983) Aluminum interaction with calmodulin. Evidence for altered structure and function from optical and enzymatic studies. Biochim Biophys Acta 744: 36–45
Suhayda CG, Haug A (1984) Organic acids prevent aluminum-induced conformational changes in calmodulin. Biochem Biophys Res Commun 119: 376–381
Author information
Authors and Affiliations
Additional information
Supported by a DFG fellowship
Part of the thesis of G. Federolf (FB 23, University of Giessen, FRG)
Rights and permissions
About this article
Cite this article
Richardt, G., Federolf, G. & Habermann, E. The interaction of aluminum and other metal ions with calcium-calmodulin-dependent phosphodiesterase. Arch Toxicol 57, 257–259 (1985). https://doi.org/10.1007/BF00324788
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00324788