Regulation and measurement of oxidative stress in apoptosis

Cells are constantly generating reactive oxygen species (ROS) during aerobic metabolism. As a consequence, each cell is equipped with an extensive antioxidant defence system to combat excessive production of ROS. Oxidative stress occurs in cells when the generation of ROS overwhelms the cell's natural antioxidant defences. There is a growing consensus that oxidative stress and the redox state of a cell plays a pivotal role in regulating apoptosis, a tightly controlled form of cell death in which a cell partakes in its own demise. More recently, a role for reactive nitrogen species (RNI) as both positive and negative regulators of cell death has been established. This review describes the major sources of ROS and RNI in a cell, the control of cell death by these species and the role of antioxidants as regulators of oxidative stress and apoptosis. Finally, the various methods that can be employed in establishing a role for both ROS and RNI in apoptosis will be discussed with particular emphasis on their intracellular detection. (C) 2002 Published by Elsevier Science B.V.