Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: An hypothesis

Production of reactive oxygen intermediates (ROI) has been thought for a lo ng time to adversely affect the physiology and survival of a cell. There is now a growing body of evidence to suggest that ROI such as superoxide anio n (0(2)(.-)) and hydrogen peroxide (H2O2) can influence the growth, as well as death, of animal cells in vitro. The observation that cells release O-2 (.-) or its dismutation product H2O2, either constitutively in the case of tumor cells or following cytokine stimulation, has led to the speculation t hat they might possibly serve as intercellular messengers to stimulate prol iferation via mechanisms common to natural growth factors. However, as the balance between cell populations in an organism is tightly controlled by th e rate of proliferation and death of constituent cells, an increase in cell numbers could reciprocally be viewed as deregulation of cell death. Hence, it is equally important-to decipher how ROI influence the response of cell s to signals that activate cell death pathway(s). We propose that ROI not o nly regulate proliferation but also affect cell sensitivity to triggers whi ch activate the cellular suicide program (apoptosis) versus those that caus e accidental (necrotic) cell death.