Cellular Oxygen Toxicity

Abstract

All forms of aerobic life are faced with the threat of oxidation from molecular oxygen (O2) and have evolved antioxidant defenses to cope with this potential problem. However, cellular antioxidants can become overwhelmed by oxidative insults, including supraphysiologic concentrations of O2 (hyperoxia). Oxidative cell injury involves the modification of cellular macromolecules by reactive oxygen intermediates (ROI), often leading to cell death. O2 therapy, which is a widely used component of life-saving intensive care, can cause lung injury. It is generally thought that hyperoxia injures cells by virtue of the accumulation of toxic levels of ROI, including H2O2 and the superoxide anion (O2-), which are not adequately scavenged by endogenous antioxidant defenses. These oxidants are cytotoxic and have been shown to kill cells via apoptosis, or programmed cell death. If hyperoxia-induced cell death is a result of increased ROI, then O2 toxicity should kill cells via apoptosis. We studied cultured epithelial cells in 95% O2 and assayed apoptosis using a DNA-binding fluorescent dye, in situ end-labeling of DNA, and electron microscopy. Using all approaches we found that hyperoxia kills cells via necrosis, not apoptosis. In contrast, lethal concentrations of either H2O2 or O2- cause apoptosis. Paradoxically, apoptosis is a prominent event in the lungs of animals injured by breathing 100% O2. These data indicate that O2 toxicity is somewhat distinct from other forms of oxidative injury and suggest that apoptosis in vivo is not a direct effect of O2.

Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation

“…Recent in vitro studies indicate that the signaling pathways used to initiate cell death do not predict the final outcome of cell necrosis or apoptosis. For example, A549 cells exposed to hyperoxia, although presenting caspase-8 and caspase-9 activation, did not undergo apoptotic cell death but presented morphological features of necrosis (10,39). However, deletion of Bid or inhibition of caspase-8 by c-FLIP protected against cell death in this model (10).…”

Superoxide Dismutase in Patients With Chronic Hepatitis C Virus Infection

“…8 Reactive oxygen metabolites are mainly produced in mitochondria during electron transport 9,10 but also, to a lesser extent, in endoplasmic reticulum, peroxisomes, and nuclear and plasma membrane. 10 ROS can damage cells by causing lipid peroxidation and oxidative damage of DNA and proteins 11 and by depleting ATP stores. 12 In the presence of metals ( …”

High levels of the cytokinin BAP suppress programmed cell death in hybrid tobacco cells (Nicotiana suaveolens*N. tabacum) expressing hybrid lethality

“…Mino et al (2005) in an early phase at 26°C. In animal cells, production of ROS acts as an early signal in the process of PCD (Kazzaz et al 1996). Moreover, in the PCD associated with the hypersensitive response (HR) in plants, ROS is produced within 1 h after infection (Draper 1997).…”