LOW-LEVELS OF REACTIVE OXYGEN SPECIES AS MODULATORS OF CELL-FUNCTION

In this paper, we present various arguments supporting the hypothesis that reactive oxygen species (ROS) could be responsible for the modula tion of various cellular functions, besides their well known toxic eff ects. We first review the recent evidence indicating that ROS are able to modulate genome expression through specific and precise mechanisms during cell activation. The role of the nitrogen reactive radicals su ch as nitric oxide is separately analyzed because of its specific role in the nervous and vascular systems. The action of the other ROS on g ene activation will then be reviewed by first looking at their possibl e involvement in the activation of transcription factors like NF-kappa B. Arguments will then be developed in favor of the implication of th e ROS in the cellular effects of PMA, TNF-alpha and other cytokines on the modulation of the genetic expression. Possible mechanisms will be presented for linking the production of the ROS with cell activation. In a general way we postulate that ROS can play a role of secondary m essengers in several cell responses to external stimuli. In the second part of the paper, we will examine the long term influence of ROS and their possible roles in cellular aging. Different links exist between ROS and aging and the relationship between them is probably indirect. We propose to consider the effect of ROS as one of the multiple chall enges that cells have to face, the cell being considered as a global s ystem which must optimize its energy expenditure for carrying out its basic functions such as turnover, differentiated phenotype functions, multiplication, defense and repair processes. This thermodynamic point of view will help to understand the effect of low ROS stresses, among others, on accelerated aging.