Reactive oxygen species and apoptosis

Abstract

Reactive oxygen species (ROS) are chemically reactive by-products of normal aerobic metabolism and xenobiotic exposure. ROS produced during different cellular reactions can be either beneficial or harmful to the cells. At physiological concentrations, ROS function as second messengers in intracellular signaling. On the other hand, aberrance in redox balance leading to excessive ROS production may cause biochemical alterations and induce oxidative modification of cellular macromolecules leading to cell death. Apoptosis or programmed cell death is a well-regulated physiological process involved in the regulation of tissue homeostasis. Induction of apoptosis by extracellular and intracellular signals triggers apoptotic-signaling pathways. The two main apoptotic pathways recognized in general are the death receptor or extrinsic pathway and the mitochondrial or intrinsic pathway. The redox state of a cell plays a major role in the regulation of apoptosis in response to any external or internal stimuli. ROS can mediate apoptosis by regulating the expression of various pro-apoptotic proteins such as caspases or anti-apoptotic proteins such as B cell lymphoma-2 (Bcl-2) and cellular FLICE-inhibitory protein (c-FLIP). Overexpression of anti-apoptotic proteins and dysregulated apoptosis is associated with various pathologies including cancer. In this chapter, we focus on the key apoptotic mechanisms and proteins that are regulated by the cellular redox state.