Hyperoxia induces DNA damage in mammalian cells

Cacciuttolo, Marco A.; Trinh, Loc; Lumpkin, Janice A.; Rao, Govind

doi:10.1016/0891-5849(93)90023-n

Cited by 173 publications

(103 citation statements)

References 11 publications

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“…The concentration of oxygen administered in these circumstances ranges from as low as 40% to as high as 100%, lung being the major organ to receive this oxidative insult. It is well documented that hyperoxia damages the DNA and other components of the cell (13). However, the signaling cascade induced by DNA damage in hyperoxia is less understood than IR-or UV-dependent DNA damage response.…”

Section: Discussionmentioning

confidence: 99%

“…Reactive oxygen species (ROS) are products of normal cellular metabolism and are generated in an elevated level in hyperoxia (12,25,54). All ROS have the potential to interact with cellular components including DNA to produce damaged bases or strand breaks (9,13,24,26). Overwhelming antioxidant defense system of the cells to counteract oxidative damage, ROS can cause damage to DNA and other macromolecules, which has been proposed to play a key role in the development of diseases such as cancer, heart diseases, neurodegenerative diseases, and diseases of the pulmonary system (2,14,47).…”

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confidence: 99%

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Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation

Kulkarni

Das²

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Elevated level of oxygen (hyperoxia) is widely used in critical care units and in respiratory insufficiencies. In addition, hyperoxia has been implicated in many diseases such as bronchopulmonary dysplasia or acute respiratory distress syndrome. Although hyperoxia is known to cause DNA base modifications and strand breaks, the DNA damage response has not been adequately investigated. We have investigated the effect of hyperoxia on DNA damage signaling and show that hyperoxia is a unique stress that activates the ataxia telangiectasia mutant (ATM)-and Rad3-related protein kinase (ATR)-dependent p53 phosphorylations (Ser6, -15, -37, and -392), phosphorylation of histone H2AX (Ser139), and phosphorylation of checkpoint kinase 1 (Chk1). In addition, we show that phosphorylation of p53 (Ser6) and histone H2AX (Ser139) depend on both ATM and ATR. We demonstrate that ATR activation precedes ATM activation in hyperoxia. Finally, we show that ATR is required for ATM activation in hyperoxia. Taken together, we report that ATR is the major DNA damage signal transducer in hyperoxia that activates ATM.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation

Kulkarni

Das²

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It easily reacts with biomolecules, such as amino acids, proteins and DNA (Cacciuttolo et al 1993). Therefore, scavenging of the hydroxyl radical is probably one of the most effective defences of a living body against various diseases.…”

Section: Inhibition Of Supercoiled Plasmid Dna Scission Induced By Hymentioning

confidence: 99%

Composition, functional properties and in vitro antioxidant activity of protein hydrolysates prepared from sardinelle (Sardinella aurita) muscle

et al. 2011

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Composition, functional properties and in vitro antioxidative activities of protein hydrolysates prepared from muscle of sardinelle (Sardinella aurita) were investigated. Sardinelle protein hydrolysates (SPH) were obtained by treatment with crude enzyme preparations from Bacillus pumilus A1 (SPHA1), Bacillus mojavensis A21 (SPHA21) and crude enzyme extract from sardinelle (Sardinella aurita) viscera (SPHEE). The protein hydrolysates SPHA1, SPHA21 and SPHEE contained high protein content 79.1%, 78.25% and 74.37%, respectively. The protein hydrolysates had an excellent solubility and possessed interfacial properties, which were governed by their concentrations. The antioxidant activities of protein hydrolysates at different concentrations were evaluated using various in vitro antioxidant assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method, reducing power assay, chelating activity, β-carotene bleaching and DNA nicking assay. All protein hydrolysates showed varying degrees of antioxidant activity. SPHA21 had the highest DPPH radical scavenging activity (89% at 6 mg/ml) and higher ability to prevent bleaching of β-carotene than SPHA1 and SPHEE (p<0.05). However, SPHEE exhibited the highest metal chelating activity (89% at 1 mg/ml) and the strongest protection against hydroxyl radical induced DNA breakage (p<0.05).

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“…Excessive ROS can directly damage cellular macro-molecules, resulting in cell cycle arrest and/or cell death [14][15][16]. In addition, exposure to hyperoxia triggers an inflammatory response, which exacerbates oxidative toxicity [17].…”

Section: Introductionmentioning

confidence: 99%

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Zaher

Miller

Morrow

et al. 2007

Free Radical Biology and Medicine

121

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Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses upon exposure to hyperoxia. We discuss in detail some of the most interesting players, such as, NF-κB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses.

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Hyperoxia induces DNA damage in mammalian cells

Cited by 173 publications

References 11 publications

Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation

Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation

Composition, functional properties and in vitro antioxidant activity of protein hydrolysates prepared from sardinelle (Sardinella aurita) muscle

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

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