Labile iron pool correlates with iron content in the nucleus and the formation of oxidative DNA damage in mouse lymphoma L5178Y cell lines.

Kruszewski, Marcin; Iwaneńko, Teresa

doi:10.18388/abp.2003_3729

Cited by 23 publications

(11 citation statements)

References 19 publications

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“…Compared to control cells, the GAK KO cells had more numerous and more intense foci positive for both phospho‐p53 and phospho‐ATM, indicating an increased number of DNA breaks in these cells (Figure A and B, respectively). Among the many agents capable of damaging the DNA, one is the non‐chelated iron ions that, while redox cycling, generate free radicals which may damage the DNA . When lysosomal homeostasis is disturbed, redox‐active iron may be released from lysosomes and upon reaching the nuclear compartment may damage the DNA .…”

Section: Resultsmentioning

confidence: 99%

Disruption of Clathrin‐Mediated Trafficking Causes Centrosome Overduplication and Senescence

Olszewski

Chandris

Park

et al. 2013

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The Hsc70 cochaperone, G cyclin-associated kinase (GAK), has been shown to be essential for the chaperoning of clathrin by Hsc70 in the cell. In this study, we used conditional GAK knockout mouse embryonic fibroblasts (MEFs) to determine the effect of completely inhibiting clathrin-dependent trafficking on the cell cycle. After GAK was knocked out, the cells developed the unusual phenotype of having multiple centrosomes, but at the same time failed to divide and ultimately became senescent. To explain this phenotype, we examined the signaling profile and found that mitogenic stimulation of the GAK KO cells and the control cells were similar except for increased phosphosylation of Akt. In addition, the disruption of intracellular trafficking caused by knocking out GAK destabilized the lysosomal membranes, resulting in DNA damage due to iron leakage. Knocking down clathrin heavy chain or inhibiting dynamin largely reproduced the GAK KO phenotype, but inhibiting only clathrin-mediated endocytosis by knocking down AP2 caused growth arrest and centrosome overduplication, but no DNA damage or senescence. We conclude that disruption of clathrin-dependent trafficking induces senescence accompanied by centrosome overduplication because of a combination of DNA damage and changes in mitogenic signaling that uncouples centrosomal duplication from DNA replication.

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Section: Resultsmentioning

confidence: 99%

Disruption of Clathrin‐Mediated Trafficking Causes Centrosome Overduplication and Senescence

Olszewski

Chandris

Park

et al. 2013

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“…While non-enzymatic antioxidant act as scavenger of ROS. For example, vitamins (E, C and A; glutathione, uric acid and melatonin (Kruszewski and Iwaneñko, 2003). Same effect are known for some aminoacids (cysteine, methionine, taurine) (Keshari and Farooqi, 2014).…”

Section: Antioxidants (Enzymatic and Non-enzymatic)mentioning

confidence: 94%

“…ROS take part in many different processes as signal molecules in animals (Schieber and Chandel, 2014) and also in plants (Kruszewski and Iwaneñko, 2003). The diversity of these processes is determined by the site of ROS production an d their interaction with a variable set of hormonal signaling compounds such as salicylic acid, abscisic acid and others including the PQ pool and GSH (Kreslavski et al, 2012;Schmitt et al, 2014).…”

Section: Oxidative Stressmentioning

confidence: 99%

Oxidative stress, reactive oxygen species, antioxidants: a review

Voronkova

Воронкова

Gorban

et al. 2018

ean

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Oxidative stress is a disturbance of the balance between the production of reactive oxygen species (ROS) and antioxidants. Oxidative stress is caused by the presence of any of a number of reactive oxygen species, which the cell is unable to counterbalance. The result is damage to one or more biomolecules including DNA, RNA, proteins and lipids. Oxidative stress has been implicated in the natural aging process as well as a variety of disease states, such as neoplastic, metabolic, neurological etc., accompanied by different complications. Risk factors of generation of oxidative stress are oxidizing species, induced by pathologies include alcohol consumption, cigarette smoking, diet, gender, geographic location specifically at high altitude and occupation. ROS are composed of superoxide, hydroxyl, peroxyl, hydroperoxyl and alkoxyl radicals, hydrogen peroxide and singlet oxygen and ozone. These compounds produced endogenous in reaction of autooxidation in respiratory chaine of bioobjects. Among exogenous sources of ROS can be listed exposure of pollutants, toxins, heavy metals, drugs with different chemical origin and effects, radiation, electromagnetic fields, alcohol, cigarette smoke, stresses, allergies, dietary factors, temperature and microscopic form of life, such as bacteria, yeasts, viruses etc. The oxidative stress in biological systems is often characterized by increase in the formation of radicals; decrease in small-molecular-weight and lipid soluble antioxidants; disturbance in cellular redox balance; oxidative damage to cellular components (biomacromolecules). The presence of oxidative stress may be tested in one of three ways: direct measurement of the ROS; measurement of the resulting damage to biomolecules; and detection of antioxidant levels. Directly measuring ROS might seem the preferred method, but many reactive oxygen species are extremely unstable and difficult to measure directly. Many markers of damage are extremely stable and therefore provide a more reliable method to measure oxidative stress. Another approach is to measure the levels of antioxidant enzymes and other redox molecules which serve to counterbalance ROS generated in the cell. At the same time, it must emphasize that oxidative stress not only has a cytotoxic effect, but also plays an important role in the modulation of messengers that regulate essential cell membrane functions, which are vital for survival. For prevention of oxidative stress cells produce or uptake antioxidants – substance significantly delays or prevents oxidation of that substrate. Antioxidants may be enzymatic and non-enzymatic in nature in which enzymatic system directly or indirectly help in defence against the ROS. Antioxidants are involved in the prevention of oxidants and ROS formation; exhibits scavenger of ROS; and repairs the oxidized molecules through sources like dietary or consecutive antioxidants. Among non-enzymatic antioxidants distinguished glutathione, α-tocopherol, ascorbic acid, beta-carotene, and uric acid; these are mostly considered to be chain-breaking antioxidants in that they interrupt the auto-catalytic spread of radical reactions. Among enzymatic antioxidants most known superoxide dismutase, catalase, glutathione-SH peroxidase. The significant correlation found between ROS, parameters of oxidative stress and pathology indicate that there is a need in finding of measures of prevention of endo- and exogenous factors provoke their generation. There is a need to continue to explore the relationship between free radicals, pathological processes and the complications of them, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of complications, in an effort to expand treatment options. Improvement of complications control seems to be a beneficial factor to decrease oxidative stress. For a better investigation of oxidative stress, it would be wise to supplement the clinical research by determination of special products typical for oxidative stress that let to understand mechanism of some pathological processes more clearly.

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“…•− + H 2 O 2 → O 2 + • OH + OH − ) and also liberates Fe 3+ from ferritin and reduces it to a Fenton reaction constituent, Fe 2+ , or liberates Fe 2+ from iron-sulfur cluster-containing enzymes (Kruszewski & Iwanenko, 2003). H 2 O 2 can be reduced to water by catalase and glutathione peroxidase.…”

Section: Oxidation-induced Dna Damagementioning

confidence: 99%

Bacterial DNA repair genes and their eukaryotic homologues: 1. Mutations in genes involved in base excision repair (BER) and DNA-end processors and their implication in mutagenesis and human disease.

Krwawicz¹,

Arczewska²,

Speina³

et al. 2007

Acta Biochim Pol

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Base excision repair (BER) pathway executed by a complex network of proteins is the major system responsible for the removal of damaged DNA bases and repair of DNA single strand breaks (SSBs) generated by environmental agents, such as certain cancer therapies, or arising spontaneously during cellular metabolism. Both modified DNA bases and SSBs with ends other than 3'-OH and 5'-P are repaired either by replacement of a single or of more nucleotides in the processes called short-patch BER (SP-BER) or long-patch BER (LP-BER), respectively. In contrast to Escherichia coli cells, in human ones, the two BER sub-pathways are operated by different sets of proteins. In this review the selection between SP- and LP-BER and mutations in BER and end-processors genes and their contribution to bacterial mutagenesis and human diseases are considered.

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Labile iron pool correlates with iron content in the nucleus and the formation of oxidative DNA damage in mouse lymphoma L5178Y cell lines.

Cited by 23 publications

References 19 publications

Disruption of Clathrin‐Mediated Trafficking Causes Centrosome Overduplication and Senescence

Disruption of Clathrin‐Mediated Trafficking Causes Centrosome Overduplication and Senescence

Oxidative stress, reactive oxygen species, antioxidants: a review

Bacterial DNA repair genes and their eukaryotic homologues: 1. Mutations in genes involved in base excision repair (BER) and DNA-end processors and their implication in mutagenesis and human disease.

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