Krako 2014 Abstract BBA - Bioenergetics
|Involvement of nitric oxide in bioenergetics: The Alzheimer's disease and the circadian rhythms. BBA - Bioenergetics 1837:e68–9|
The activity of melatonin influences almost all body cells and, as recently recognized, with bioenergetic consequences. Our work indicated that in HaCaT cells, melatonin administrated at physiological concentration (HaCmel +), modulates energy production following a pathway involving Nitric Oxide (NO). As a signalling molecule, NO presents a wide spectrum of targets, differently influenced depending on the NOS isoform implicated, and on the amount/localisation of NO produced. Our data show that in HaCmel + cells an increase of nNOS expression occurs, leading to accumulation of nitrite and nitrate and consistently oxygen consumption is slightly depressed.
Mitochondrial complex IV is in fact reversibly inhibited by NO, whose increase induced by melatonin appears compatible with a “mild” OXPHOS depression, characteristic of the physiological variation of energy demand related to circadian rhythms [1,2]. The issue of cell energy metabolism has been also readdressed to the 7PA2 cell line, a model of the Alzheimer's disease (AD). The biochemical characterisation of 7PA2 cells, expressing the mutated human APP protein, showed a marked decrease of mitochondrial function, evaluated by measuring oxygen consumption, mitochondrial membrane potential and ATP production. The observed nitrite/nitrate accumulation points to the involvement of NO also in this pathological state, in agreement with the high activity of iNOS found in neurons affected by AD . Interestingly, as a common denominator, in both HaCmel + and 7PA2 cells lactate levels increased with respect to controls, being this effect higher in the AD cells. The Warburg effect was evaluated in the presence of OXPHOS inhibitors showing that cells are able to compensate OXPHOS failure by a glycolitic burst; in the 7PA2 cells, however, the glycolytic increment appears insufficient to compensate for the energy failure as indicated by the overall ATP deficit.
Copyright © 2014 Published by Elsevier B.V.
• O2k-Network Lab: IT Roma Sarti P
Labels: Pathology: Alzheimer's
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell, Other cell lines
Enzyme: Complex IV;cytochrome c oxidase
a-Sapienza Univ, Rome; b-Dept Biochem Sc, Inst Pasteur-Fondazione Cenci Bolognetti, Sapienza Univ; c-CNR, Inst Mol Biol Pathol, Rome; d-Scuola Normale Superiore, Pisa; eCNR, Inst Mol Biol Pathol; Scuola Normale Superiore, Pisa; g-Europ Brain Research Inst — “Rita Levi-Montalcini”; Italy. - [email protected]