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

Abstract

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.

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

“…Similarly, multiple mechanism(s) may underlie HSPmediated inhibition of cisplatin ototoxicity. In other systems, HSPs protect cells against damage-induced death by preventing the accumulation and aggregation of damaged proteins, as well as by promoting proper re-folding of denatured proteins (Jolly and Morimoto 2000;Yamamoto et al 2000;Martindale and Holbrook 2002;Mayer and Bukau 2005;Kastle and Grune 2012). The protection conferred by HSPs is not limited to these "chaperone" activities; HSPs also inhibit lipid peroxidation and oxidative damage to DNA (Park et al 1998;Su et al 1999;Martindale and Holbrook 2002).…”

“…In other systems, HSPs protect cells against damage-induced death by preventing the accumulation and aggregation of damaged proteins, as well as by promoting proper re-folding of denatured proteins (Jolly and Morimoto 2000;Yamamoto et al 2000;Martindale and Holbrook 2002;Mayer and Bukau 2005;Kastle and Grune 2012). The protection conferred by HSPs is not limited to these "chaperone" activities; HSPs also inhibit lipid peroxidation and oxidative damage to DNA (Park et al 1998;Su et al 1999;Martindale and Holbrook 2002). In addition, HSPs have been shown to inhibit multiple pro-apoptotic signaling events (Jaattela et al 1998;Beere et al 2000;Pandey et al 2000a, b;Concannon et al 2001Concannon et al , 2003Tsuchiya et al 2003;Stankiewicz et al 2005;Rodina et al 2007;Jiang et al 2009;Evans et al 2010;Pasupuleti et al 2010).…”

“…Many HSPs act as molecular chaperones, promoting the proper folding, transport, subcellular localization, and activity of client proteins. Nonlethal heat shock preconditioning results in upregulation of inducible HSP family members, which are protective against a wide variety of cellular stresses (Martindale and Holbrook 2002;Richter et al 2010;Rampelt et al 2012). Previously, we showed that heat shock inhibits both cisplatin-and aminoglycoside-induced hair cell death (Cunningham and Brandon 2006).…”

Busulfan-induced senescence is dependent on ROS production upstream of the MAPK pathway

“…The activation of the Erk-p38 MAPK pathway is likely attributable to the oxidative stress induced by BU, because Erk and p38 are sensitive to ROS [16,17,31,36]. It has been shown that the major route of BU metabolism is through GSH-S-transferase catalyzed conjugation to GSH [18,19].…”

Oxidative stress stimulates IL‐4 and IL‐6 production in mast cells by an APE/Ref‐1‐dependent pathway

“…ROS, whether produced as a consequence of normal cell function or derived from external sources, elicit a wide spectrum of responses ranging from proliferation to growth arrest and cell death [25]. Low doses of ROS, particularly H 2 O 2 , are mitogenic and promote cell proliferation, while high doses result in either temporary or permanent growth arrest and ultimately cause cell death [26]. The present study demonstrates that oxidative stimuli could trigger cytokine expression and secretion, and could potentiate Fc 4 RI stimulation in RBL-2H3 cells.…”