cAMP controls oxygen metabolism in mammalian cells.
The impact of cAMP on ROS-balance in human and mammalian cell cultures was studied. cAMP reduced accumulation of ROS induced by serum-limitation, under conditions in which there was no significant change in the activity of scavenger systems. This effect was associated with cAMP-dependent activation of the NADH-ubiquinone oxidoreductase activity of complex I. In fibroblasts from a patient a genetic defect in the 75 kDa FeS-protein subunit of complex I resulted in inhibition of the activity of the complex and enhanced ROS production, which were reversed by cAMP. A missense genetic defect in the NDUFS4 subunit, putative substrate of PKA, suppressed, on the other hand, the activity of the complex and prevented ROS production.
Piccoli
Claudia
C
Department of Biomedical Science, University of Foggia, Foggia, Italy.
Scacco
Salvatore
S
Bellomo
Francesco
F
Signorile
Anna
A
Iuso
Arcangela
A
Boffoli
Domenico
D
Scrima
Rosella
R
Capitanio
Nazzareno
N
Papa
Sergio
S
D000818:Animals; D002460:Cell Line; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000502:physiology*; D042967:Electron Transport Complex I / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D016895:Culture Media, Serum-Free; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D042967:Electron Transport Complex I; D005978:Glutathione