Chapter 19 Oxidative stress signaling

Hasem Habelhah; Ze'ev Ronai

doi:10.1016/S1568-1254(01)80021-8

Oxygen is an essential molecule for metabolism and energy generation in aerobic organisms and is the primary source for the generation of reactive oxygen species (ROS). ROS are generated in the mitochondria as a by-product of the electron transport chain, as well as by nonmitchondrial enzymes, such as oxidases or peroxidases. Excess ROS is harmful because of its potent ability to interact with, and modify, a wide range of cellular macromolecules implicated in cytotoxicity and mutagenic damage. Conversely, a low level of ROS is necessary to maintain cell proliferation and serve as intracellular signaling molecules. Accordingly, the level of ROS is tightly controlled by several enzymatic (example, superoxide dismutases, glutathione peroxidase, glutathione reductase and catalase) and non-enzymatic (glutathione and vitamins C and E) antioxidants. To offset the oxidant effects and to restore a state of redox balance, cells often activate or silence genes encoding regulatory transcription factors, antioxidant defense enzymes and structural proteins. ROS, which is secreted by specialized cells including macrophages and neutrophils, serves as a key player in host defense against pathogens. Control of ROS levels is one of the key determinants in maintaining cell growth and death. This chapter discusses the mechanisms underlying the cellular response to ROS at the level of signal transduction and gene expression and their implications for cell growth, senescence, and death.

Chapter 19 Oxidative stress signaling

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