Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein.
Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.
Friguet
B
B
Unité de Biochimie Cellulaire, Institut Pasteur, Paris, France.
Szweda
L I
LI
D000447:Aldehydes / Q000494:pharmacology*; D000817:Anilino Naphthalenesulfonates / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D009097:Multienzyme Complexes / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex
D000447:Aldehydes; D000817:Anilino Naphthalenesulfonates; D003432:Cross-Linking Reagents; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D005954:Glucosephosphate Dehydrogenase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D005974:Glutamate-Ammonia Ligase; C027576:4-hydroxy-2-nonenal