Amino acid, peptide, and protein hydroperoxides and their decomposition products modify the activity of the 26S proteasome

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Show simple item record Gracanin, Michelle en_US Lam, Magdalena en_US Morgan, Philip en_US Hawkins, Clare en_US Davies, Michael en_US Rodgers, Ken en_US
dc.contributor.editor en_US 2012-02-02T05:26:56Z 2012-02-02T05:26:56Z 2011 en_US
dc.identifier 2010001149 en_US
dc.identifier.citation Gracanin Michelle et al. 2011, 'Amino acid, peptide, and protein hydroperoxides and their decomposition products modify the activity of the 26S proteasome', Pergamon, vol. 50, no. 2, pp. 389-399. en_US
dc.identifier.issn 0891-5849 en_US
dc.identifier.other C1UNSUBMIT en_US
dc.description.abstract Proteins are major biological targets for oxidative damage within cells because of their high abundance and rapid rates of reaction with radicals and singlet oxygen. These reactions generate high yields of hydroperoxides. The turnover of both native and modified/damaged proteins is critical for maintaining cell homeostasis, with this occurring via the proteasomal and endosomal?lysosomal systems; the former is of particular importance for intracellular proteins. In this study we have examined whether oxidation products generated on amino acids, peptides, and proteins modulate 26S proteasome activity. We show that oxidation products, and particularly protein hydroperoxides, are efficient inhibitors of the 26S proteasome tryptic and chymotryptic activities, with this depending, at least in part, on the presence of hydroperoxide groups. Removal of these species by reduction significantly reduces proteasome inhibition. This loss of activity is accompanied by a loss of thiol residues, but an absence of radical formation, consistent with molecular, rather than radical, reactions being responsible for proteasome inhibition. Aldehydes also seem to play a role in the inhibition of chymotryptic activity, with this prevented by treatment with NaBH4, which reduces these groups. Inhibition occurred at hydroperoxide concentrations of = 1 ?M for oxidized amino acids and peptides and = 10 ?M for oxidized proteins, compared with ca. 100 ?M for H2O2, indicating that H2O2 is a much less effective inhibitor. These data indicate that the formation of oxidized proteins within cells may modulate cell function by interfering with the turnover of native proteins and the clearance of modified materials. en_US
dc.language en_US
dc.publisher Pergamon en_US
dc.relation.isbasedon en_US
dc.title Amino acid, peptide, and protein hydroperoxides and their decomposition products modify the activity of the 26S proteasome en_US
dc.parent Free Radical Biology & Medicine en_US
dc.journal.volume 50 en_US
dc.journal.number 2 en_US
dc.publocation Oxford, UK en_US
dc.identifier.startpage 389 en_US
dc.identifier.endpage 399 en_US SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 030400 en_US
dc.personcode 0000066087 en_US
dc.personcode 0000066088 en_US
dc.personcode 0000066089 en_US
dc.personcode 111642 en_US
dc.personcode 0000066090 en_US
dc.personcode 0000045917 en_US
dc.percentage 50 en_US Medicinal and Biomolecular Chemistry en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity en_US
dc.description.keywords Hydroperoxide; Protein oxidation; Proteasome; Protein turnover; Singlet oxygen en_US

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