Cellular response to oxidative stress: Signaling for suicide and survival *

By J. Martindale, N. Holbrook. Journal of Cellular Physiology, 2002

2,374 citations recorded by the source corpus.

Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley‐Liss, Inc.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e2aeefb49567d38ea01c54aae960ddff02d97aeb

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In Molecular Biology

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Citations in the corpus

• TIGAR, a p53-inducible regulator of glycolysis and apoptosis. (2006, background): “However, in light of previous studies showing that increased ROS levels can signal to stabilize and activate p53 (Chen et al., 2003; Martindale and Holbrook, 2002), we examined the relationship between TIGAR and p53 more closely.”
• Regulation of reactive oxygen species generation in cell signaling (2011, background): “Recent evidences convincingly argue that these ROS play an important role in numerous physiological and pathological processes (Droge, 2002; Martindale and Holbrook, 2002).”
• Cellular mechanisms of Cnidarian bleaching: stress causes the collapse of symbiosis (2008, background): “Oxidative stress functions in animal systems in modulating cell death/cell survival pathways (Martindale and Holbrook, 2002) and in innate immune responses to microbes (Fang, 2004).”
• Activation of the PI3K/Akt pathway and chemotherapeutic resistance. (2002, background): “These forms of cellular stress include heat shock, administration of ultraviolet light, ischemia, hypoxia, hypoglycemia, and oxidative stress (Chen et al., 2001; Crossthwaite et al., 2002; Ma et al., 2001; Martindale and Holbrook, 2002; Ouyang et al., 2000; Sakurai et al., 2001; Shaw et al., 1998).”
• Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. (2006, background): “The major signaling pathways known to be involved in regulating the cellular response to oxidative stress include MAPKs, PI3-kinase/Akt pathway, heat shock protein expression, p53 signaling, and NF-κB signaling (Martindale and Holbrook, 2002).”
• A review of the interaction among dietary antioxidants and reactive oxygen species. (2007, background): “For example, ERK facilitates hypoxia-induced apoptosis of macrophages and cisplatin-induced apoptosis of HeLa cells [11].”
• ROS and p53: a versatile partnership. (2008, background): “Cellular processes in which ROS are involved range from proliferation to growth arrest or senescence and cell death [4,5].”
• Calcium and ROS: A mutual interplay (2015, background): “There is increasing evidence that in addition to the detrimental effects of high ROS levels exceeding the cellular antioxidant capacity, the cell is able to generate ROS in lower amounts that act as important signaling molecules controlling cell proliferation and cell death, cellular migration, vasc”
• Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. (2016, background): “extracellular-signal regulated kinases (ERKs), by phosphorylation, or by increasing the expression of cyclin D1 and activation of c-JUN which are instrumental in growth and survival of cancer cells [37, 38].”
• Oxidative stress in marine environments: biochemistry and physiological ecology. (2006, background): “Whereas high levels of oxidative stress cause cell necrosis, lower levels either cause DNA damage and cell-cycle arrest or initiate apoptosis (8, 41).”