title: Activation of the cAMP cascade in human fibroblast cultures rescues the activity of oxidatively damaged complex I.
abstract: A study of the relationship between cAMP/PKA-dependent phosphorylation and oxidative damage of subunits of complex I of the mitochondrial respiratory chain is presented. It is shown that, in fibroblast cultures, PKA-mediated phosphorylation of the NDUFS4 subunit of complex I rescues the activity of the oxidatively damaged complex. Evidence is presented showing that this effect is mediated by phosphorylation-dependent exchange of carbonylated NDUFS4 subunit in the assembled complex with the de novo synthesized subunit. These results indicate a potential use for β-adrenoceptor agonists in preventing/reversing the detrimental effects of oxidative stress in the mitochondrial respiratory system.
authors.affiliation: Section of Medical Biochemistry, Department of Basic Medical Sciences, University of Bari, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: De Rasmo
authors.forename: Anna
authors.initials: A
authors.lastname: Signorile
authors.forename: Maria
authors.initials: M
authors.lastname: Larizza
authors.forename: Consiglia
authors.initials: C
authors.lastname: Pacelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cocco
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D050050:Protein Carbonylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D015290:Second Messenger Systems; D020122:tert-Butylhydroperoxide
chemical_list: D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D009245:NADH Dehydrogenase; D017868:Cyclic AMP-Dependent Protein Kinases; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human