1. Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome
- Author
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Edyta Heropolitanska Pliszka, Małgorzata Pac, Mateusz Maciejczyk, Bożena Mikołuć, Barbara Pietrucha, Halina Car, and Radosław Motkowski
- Subjects
Prx 3, mitochondrial peroxiredoxin 3 ,DNA Repair ,LCLs, lymphoblastoid cell lines ,Fe, iron ,Review Article ,Biochemistry ,Antioxidants ,Nijmegen breakage syndrome (NBS) ,Glx, glyoxal ,Bloom syndrome ,mtETC, mitochondrial electron transport chain ,lcsh:QH301-705.5 ,Cu, copper ,8-OHdG, 8-hydroxy-2-deoxyguanosine ,ox-LDL, oxidised low-density lipoprotein ,food and beverages ,DS, Down Syndrome ,UA, uric acid ,Lipoproteins, LDL ,CS, Cockayne Syndrome ,Poly(ADP-ribose) Polymerases ,lcsh:Medicine (General) ,Bloom Syndrome ,GSH-Px, glutathione peroxidase ,G6PD, glucose-6 phosphate dehydrogenase ,DNA damage ,TOP1mt, mitochondrial topoisomerase I ,FA, Fanconi anaemia ,mTOR, mammalian target of rapamycin ,XP, Xeroderma pigmentosum ,DDR, DNA damage response ,03 medical and health sciences ,Oxidative damage ,Humans ,HO, heme oxygenase ,BS, Bloom syndrome ,NOX4, NADPH oxidase 4 ,Nijmegen Breakage Syndrome ,Ataxia-telangiectasia (A-T) ,DNA-PKcs, DNA-dependent protein kinase catalytic subunit ,MDA, malondialdehyde ,XO, xanthine oxidase ,GSSG, oxidised glutathione ,medicine.disease ,LWMA, low molecular weight antioxidants ,030104 developmental biology ,DSBs, double strand breaks ,Ataxia-telangiectasia ,AA, ascorbic acid ,GSSG-R, glutathione reductase ,CAT, catalase ,HR, homologous recombination ,PARP, Poly (ADP-ribose) polymerases ,Reactive Oxygen Species ,Nijmegen breakage syndrome ,0301 basic medicine ,MGlx, methylglyoxal ,GSH, reduced glutathione ,PDTC, ammonium pyrrolidinedithiocarbamate ,Clinical Biochemistry ,Mitochondrion ,medicine.disease_cause ,ALA, α-lipolic acid ,HGS, Hutchinson-Gilford syndrome ,LOX, lipoxygenase ,t-butyl-OOH, tert-Butyl-hydroperoxide ,CBS, chromosomal breakage syndromes ,NAC, N-acetyl-L-cysteine ,lcsh:R5-920 ,NADPH oxidase ,GPx, glutathione peroxidase ,biology ,mROS, mitochondrial reactive oxygen species ,Zn, zinc ,Mitochondria ,AOA3, ataxia with oculomotor apraxia type 3 ,PKC-δ, protein kinase C ,X/XO, xanthine/xanthine oxidase ,NADPH Oxidase 4 ,Signal Transduction ,Premature aging ,Bloom syndrome (BS) ,AOS, antioxidant defense systems ,NAD+, oxidised nicotinamide adenine dinucleotide ,Se, selenium ,Ataxia Telangiectasia ,ROS, reactive oxygen species ,SOD, superoxide dismutase ,GST, glutathione-S-transferase ,medicine ,Q10, ubiquinone ,IR, ionising radiation ,Organic Chemistry ,A-T, Ataxia-telangiectasia ,mtDNA, mitochondrial DNA ,POLG, polymerase gamma ,Oxidative Stress ,NBS, Nijmegen breakage syndrome ,Gene Expression Regulation ,lcsh:Biology (General) ,ATM, Ataxia Telangiectasia Mutated gene ,NOX2, NADPH oxidase 2 ,biology.protein ,Cancer research ,WS, Werner syndrome (WS) ,SMG-1, suppressor with morphological effect on genitalia family member ,ATR, ATM and Rad3-related ,Oxidative stress ,DNA Damage - Abstract
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model., Graphical abstract fx1
- Published
- 2017
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