title: Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium.
abstract: The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two to three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.
authors.affiliation: Liver Study Unit, Veterans Administration Medical Center, Omaha, Nebraska.
authors.forename: R B
authors.initials: RB
authors.lastname: Jennett
authors.forename: A
authors.initials: A
authors.lastname: Saffari-Fard
authors.forename: M F
authors.initials: MF
authors.lastname: Sorrell
authors.forename: S L
authors.initials: SL
authors.lastname: Smith
authors.forename: D J
authors.initials: DJ
authors.lastname: Tuma
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D002417:Cattle; D004533:Egtazic Acid; D008968:Molecular Conformation; D012710:Serum Albumin, Bovine; D013997:Time Factors; D014268:Trifluoperazine
chemical_list: D002147:Calmodulin; D014268:Trifluoperazine; D012710:Serum Albumin, Bovine; D004533:Egtazic Acid; D000079:Acetaldehyde; D002118:Calcium