title: Limited degradation of oxidized calmodulin by proteasome: formation of peptides.
abstract: Oxidized proteins are recognized and degraded preferentially by the proteasome. This is true for numerous proteins including calmodulin (CaM). The degradation of CaM was investigated in a human fibroblast cell line under conditions of oxidative stress. Low molecular CaM fragments or peptides were found under such conditions. In in vitro experiments it was investigated whether this CaM breakdown product formation is induced by protein oxidation or is due to a limited proteolysis-derived degradation by the 20S proteasome. Native unoxidized CaM was not degraded by 20S proteasome, oxidized CaM was degraded in a time- and H2O2 concentration-dependent manner. Peptides of similar molecular weight were detected in isolated calmodulin as in oxidatively stressed fibroblasts. The peptides were identified using isolated calmodulin. Therefore, in oxidatively stressed fibroblasts and in vitro CaM is forming oxidation-driven fragments and proteasomal cleavage peptides of approximately 30 amino acids which undergo a slow or no degradation.
authors.affiliation: Research Institute for Environmental Medicine gGmbH at the Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Strosova
authors.forename: Peter
authors.initials: P
authors.lastname: Voss
authors.forename: Martina
authors.initials: M
authors.lastname: Engels
authors.forename: Lubica
authors.initials: L
authors.lastname: Horakova
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
mesh_terms: D000595:Amino Acid Sequence; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013997:Time Factors
chemical_list: D002147:Calmodulin; D010455:Peptides; D006861:Hydrogen Peroxide; D046988:Proteasome Endopeptidase Complex