Oxidative stress response

Reactive oxygen species (also called ROS) are one of the main causes of cellular stress. The survival of a cell depends on a balance between oxidants (oxygen and ROS) and antioxidants (enzymes and proteins such as glutathione, catalase or superoxide dismutases) that can be dysfunctional[19]. Most of the time, the cell is able to fight against oxidative stress and to promote its survival but, as for the previous cellular stresses mentioned, it happens that the oxidative:antioxidant balance is too deregulated for the cell to correct it. It will then enter processes of apoptosis or necrosis[19, 20, 21].

The best known ROS are hydrogen peroxide (H202, also called hydrogen peroxide), hydroxyl radicals (OH-) and nitric oxide (NO-). They have various origins, intra- or extracellular. The largest source of intracellular oxidants is our mitochondria and its respiratory chain: when it produces energy, it also produces ROS which are generally treated with superoxide dismutases. In addition to this intracellular source, our lifestyle greatly influences the generation of ROS. External causes include prolonged exposure to UV, pollution, pesticides, tobacco, alcohol, an unbalanced diet, too much sport, stress, or a nutritional deficiency in one or more antioxidants.

The response to oxidative stress combines a specific response and mechanisms common to other stresses, such as activation of chaperone protein synthesis[22] or NF-κB and p53[23]. It is not yet very clear how apoptosis induction takes place but it seems that H2O2 activates a system called Fas-FasL, which in turn induces caspase activation[24]. NO•, on the other hand, seems to be capable of inactivating certain antioxidant enzymes such as superoxide dismutase[25]. Interestingly, ROS could also activate a different cell death mechanism, necrosis. This occurs through the inactivation of caspases, normally pro-apoptotic molecules whose absence of stimulation will force the cell to turn to another form of death. The commitment to necrosis can also be explained by a decrease in ATP in the cell, inherent in damage to the mitochondria by too many oxidants[26]. Finally, a last mode can be engaged, that of autophagy, although the mechanisms leading to it are not yet clear[27].