Effects of modulations of the energetic metabolism on the mortality of cultured cells.
Since cells are open systems which exchange material with their surroundings, they can be considered as open systems far from equilibrium and in this way, they follow the principles of thermodynamics of open systems. This approach stresses the fact that cells optimize their use of energy according to their functions. However, with time and/or under environmental challenges, cells can reorganize themselves at other lower levels of energy production and utilization (Toussaint et al. (1991) Mech. Ageing Dev. 61, 45-64). Considered as optimized systems, cells can adapt their behaviours according to the balance between, on one side, their energetic potential and the level of their defence systems, and on the other side, the intensity of the stress. Mainly three types of behaviour can be theoretically predicted. If the stresses are very low, the damages generated are instantaneously repaired and the cellular system remains at its steady state of energy production and utilization. If the stresses are of an intermediary intensity, it is predicted that the cell can leave its steady state of energy production and utilization and find a new one characterized by a lower level of entropy production and a higher level of errors. Third, if the stresses are of a very high intensity which can be cytotoxic, the level of the energetic potential of the cell is directly related to cell survival. We tested the latter prediction in the present work in two ways. First, the level of energy production was lowered by partially uncoupling the mitochondria. Then the effect of stresses under tert-butylhydroperoxide or ethanol was investigated in order to look for a synergistic effect on cell death with the mitochondria uncoupling. Secondly, the effect of a modification of the energetic sources during the stress was tested. Besides a protective effect found with specific defence systems, the presence of energetic metabolites such as D-glucose, pyruvate/malate, glutamate/malate, was tested and found to be protective. The effect of a stimulator of the energetic metabolism, naftidrofuryl oxalate, was also investigated and found protective. The experimental data provide good evidence that energetic factors can modulate the resistance of cells to various stresses.
Toussaint
O
O
Laboratoire de Biochimie Cellulaire, Facultés Universitaires N.-D. de la Paix, Namur, Belgium.
Houbion
A
A
Remacle
J
J
D000255:Adenosine Triphosphate / Q000032:analysis; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D016923:Cell Death; D002478:Cells, Cultured / Q000378:metabolism; D003470:Culture Media; D004734:Energy Metabolism; D000431:Ethanol; D006801:Humans; D010545:Peroxides; D020122:tert-Butylhydroperoxide
D003470:Culture Media; D010545:Peroxides; D000431:Ethanol; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D020122:tert-Butylhydroperoxide