Role of superoxide in deoxyribonucleic acid strand scission

Lesko, Stephen A.; Lorentzen, Ronald J.; Ts’o, Paul O. P.

doi:10.1021/bi00554a029

Cited by 275 publications

(105 citation statements)

References 39 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Another consequence of leaky lysosomes and cellular acidification is the reactivation of DNase II, which is usually inhibited in cancer cells (Daoust and Amano, 1963;Taper, 1967Taper, , 1980Taper et al, 1971Taper et al, , 1981. H 2 O 2 and ROS can also alter nucleosides, inhibit DNA synthesis, induce DNA strand breaks, and inhibit DNA repair (Ishida and Takahashi, 1975;Morgan et al, 1976;Lesko et al, 1980;Bram and Fridovich, 1981;Lupulescu, 1991;Menon et al, 1998). Together, these actions explain the decreased Feulgen staining in VCtreated cells (Figs.…”

Section: Cytotoxicity Of Ascorbatementioning

confidence: 99%

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Gilloteaux¹,

Jamison²,

Arnold³

et al. 2005

Anat. Rec.

View full text Add to dashboard Cite

Feulgen and actin-phalloidin staining as well as gel electrophoresis have been employed in conjunction with cell ultrastructure to describe the effects of 1-, 2-, and 4-hr ascorbate (VC), menadione (VK 3 ), and ascorbate:menadione (VC:VK 3 ) treatments on the T24 human bladder carcinoma cell line. T24 cells exposed to VC alone display blebs and other superficial membrane defects related to membrane alterations and to superficial cytoskeleton changes. VK 3 treatment damages the cell nucleus and organelles, leads to the redistribution of the organelles in the perikaryon as a consequence of cytoskeletal damage, and results in cytoplasmic self-excisions. After VC:VK 3 treatment, the cells show exaggerated alterations characteristic of each vitamin treatment alone, including damaged mitochondria, self-excision of organelle-free pieces of cytoplasm, and extrusion of the perikaryon containing a nucleus surrounded by the damaged organelles. The nuclear envelope appears intact and contains chromatin that decondenses and dissipates. During the cellular demise that concludes with apparent karyolysis, the cells significantly decrease their size and alter their shape. However, the cisterns of rough endoplasmic reticulum are undamaged, but may become dilated. Since the cellular phenomena leading to cell death differ morphologically from apoptosis and necrosis, but entail selfcutting without nuclear bodies, this new form of cell death was called autoschizis. In addition, gel electrophoresis and Feulgen staining demonstrate that autoschizis is accompanied by random DNA degeneration.

show abstract

Section: Cytotoxicity Of Ascorbatementioning

confidence: 99%

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Gilloteaux¹,

Jamison²,

Arnold³

et al. 2005

Anat. Rec.

View full text Add to dashboard Cite

show abstract

“…However, it can slowly oxidize the reduced flavins of many redox enzymes, thereby generating a mixture of superoxide (O 2 . ) and hydrogen peroxide (H 2 O 2 ) (1-3 (8,9). Oxidative DNA damage is therefore ascribed to a fourth oxygen species, the hydroxyl radical (HO ⅐ ).…”

mentioning

confidence: 99%

“…That reductant has not been identified. Superoxide itself is capable of reducing free iron and functions in that capacity in some in vitro Fenton systems (8,9,18). However, the intracellular concentration of superoxide is so low (ϳ10 Ϫ10 M) (19,20), and its reduction of bound iron so slow (ϳ10 5 M Ϫ1 s Ϫ1 ) (21), that the predicted half-time for this reaction in vivo is Ͼ10 h, far too long to be physiologically relevant.…”

mentioning

confidence: 99%

Reduced Flavins Promote Oxidative DNA Damage in Non-respiringEscherichia coli by Delivering Electrons to Intracellular Free Iron

Woodmansee

Imlay

2002

Journal of Biological Chemistry

128

163

View full text Add to dashboard Cite

When cells are exposed to external H 2 O 2 , the H 2 O 2 rapidly diffuses inside and oxidizes ferrous iron, thereby forming hydroxyl radicals that damage DNA. Thus the process of oxidative DNA damage requires only H 2 O 2 , free iron, and an as-yet unidentified electron donor that reduces ferric iron to the ferrous state. Previous work showed that H 2 O 2 kills Escherichia coli especially rapidly when respiration is inhibited either by cyanide or by genetic defects in respiratory enzymes. In this study we established that these respiratory blocks accelerate the rate of DNA damage. The respiratory blocks did not substantially affect the amounts of intracellular free iron or H 2 O 2 , indicating that that they accelerated damage because they increased the availability of the electron donor. The goal of this work was to identify that donor. As expected, the respiratory inhibitors caused a large increase in the amount of intracellular NADH. However, NADH itself was a poor reductant of free iron in vitro. This suggests that in non-respiring cells electrons are transferred from NADH to another carrier that directly reduces the iron. Genetic manipulations of the amounts of intracellular glutathione, NADPH, ␣-ketoacids, ferredoxin, and thioredoxin indicated that none of these was the direct electron donor. However, cells were protected from cyanide-stimulated DNA damage if they lacked flavin reductase, an enzyme that transfers electrons from NADH to free FAD. The K m value of this enzyme for NADH is much higher than the usual intracellular NADH concentration, which explains why its flux increased when NADH levels rose during respiratory inhibition. Flavins that were reduced by purified flavin reductase rapidly transferred electrons to free iron and drove a DNA-damaging Fenton system in vitro. Thus the rate of oxidative DNA damage can be limited by the rate at which electron donors reduce free iron, and reduced flavins become the predominant donors in E. coli when respiration is blocked. It remains unclear whether flavins or other reductants drive Fenton chemistry in respiring cells.

show abstract

“…The maintenance of cell redox state is important to cell viability [43]. The increased level of reactive species can lead to oxidative damage to a vast number of biological molecules, as DNA [44][45][46] There is a grand amount of theories about aging process, at least 300 theories according Medvedev [53]. In 1956, Harman proposed in his "free radical theory of aging" that the damage of biomolecules that occurs during aging is due oxidative stress, ROS increments [54].…”

Section: Reactive Species In Mitochondriamentioning

confidence: 99%

“…The maintenance of cell redox state is important to cell viability [43]. The increased level of reactive species can lead to oxidative damage to a vast number of biological molecules, as DNA [44][45][46], proteins [47], lipids [48], including membranes [3] leading to a range of pathologies, as cancer [36], neurological disease [49], cardiac disease [50,51], inflammation process [52] and aging.…”

Section: Cellular Respiration and Generation Of Reactive Species In Tmentioning

confidence: 99%

Oxidative Stress: Noxious but Also Vital

Bagatini¹,

Jaques²,

Oliveira³

et al. 2018

Novel Prospects in Oxidative and Nitrosative Stress

View full text Add to dashboard Cite

The imbalance between reactive oxygen species (ROS) production and antioxidant defenses determines the condition called oxidative stress. When there is an increase in ROS production or a decrease in the antioxidant defenses, this systemic antioxidant/pro-oxidant imbalance may lead to the accumulation of oxidative damage, which, in turn, may lead to a modification of biomolecules. These consist of reactions resulting in protein adducts, DNA oxidation, and formation of lipid peroxides, which, in turn, reduce the cellular functional capacity and increase the risk of disease development. The body has natural scavenging systems against free radicals and other reactive species. However, sometimes the endogenous antioxidant capacity is exceeded by the production of ROS. When this occurs, exogenous antioxidants exert important function for the human health. These bioactive compounds act preventing and neutralizing the formation of new reactive species and free radical s .I ns o m ec a s e s ,a n increase of ROS can help the host to resolve an infection or even to control the tumor growth. Finally, the levels of ROS can be perceived by signal transduction pathways involving known targets(i.e.,p53,Ras,andNF-κB) and regulate physiopathological events such as the cellular cycle, apoptosis, and inflammation.Keywords: reactive species, cellular oxidation, antioxidant system, health, disease © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cellular respiration and generation of reactive species in the mitochondria: implications in cell viability and agingOxidative phosphorylation is the center of energy metabolism in plants, animals and several microbial life forms [1]. In eukaryotes, this process occurs in mitochondria. The mitochondria is a cytoplasmic organelle surrounded by two membranes, outer and inner membrane, which main function is the production of most of the phosphate compounds necessary for the energetic balance of the cell. In addition, other functions such as the regulation of the body'sheatgeneration [2][3][4] programmed cell death [5][6][7], reactive oxygen species (ROS) generation and cell signaling [8] is also associated with mitochondria. Cellular vitality is directly related to mitochondria, and mitochondrial dysfunctions are frequent causes of accidental cell death [5,[9][10][11], cancer [12, 13], diabetes [14][15][16] and neurodegenerative diseases [17][18][19], among others.The characterization of the respiratory electron chain could be performed in studies using the fractionation of its components by certain detergents that at low concentrations break the interactions between proteins and lipids in the membranes, leaving associations between proteins intact [20]. In electron transport chain, through this process, four protein complexes were found....

show abstract

Role of superoxide in deoxyribonucleic acid strand scission

Cited by 275 publications

References 39 publications

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Reduced Flavins Promote Oxidative DNA Damage in Non-respiringEscherichia coli by Delivering Electrons to Intracellular Free Iron

Oxidative Stress: Noxious but Also Vital

Contact Info

Product

Resources

About