Oxidative Stress, Human Genetic Variation, and Disease

Forsberg, Lars; Fairé, Ulf dé; Morgenstern, Ralf

doi:10.1006/abbi.2001.2295

Cited by 269 publications

(185 citation statements)

References 126 publications

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“…increase in serum copper (Schwartz & Weiss, 1990). Although we investigated plasma copper because of its contribution to antioxidant activity via its contribution to the serum antioxidant caeruloplasmin (Al-Timimi & Dormandy, 1977;Goldstein et al, 1979;Gutteridge et al, 1980;Taylor & Oey, 1982) and as a coenzyme for super-oxide dismutase (Fridovich, 1978;Forsberg et al, 2001), paradoxically, one possible explanation for our unanticipated observation is the pro-oxidant activity of copper. Although 95 per cent of plasma copper is incorporated into ceruloplasmin, copper has the potential to have a pro-oxidative effect in vivo by catalysing hydroxyl radical formation (Halliwell & Gutteridge, 1984), accelerating auto-oxidation reactions and lipid peroxidation (Halliwell, 1996), and promoting the pro-oxidative activity of vitamin C (Halliwell, 1996).…”

Section: Coppermentioning

confidence: 99%

“…Copper is also involved in antioxidant defences both extracellularly, when bound as ceruloplasmin (Al-Timimi & Dormandy, 1977;Goldstein et al, 1979;Gutteridge et al, 1980;A.D., Taylor & Oey, 1982), and intracellularly as a coenzyme for superoxide dismutase (Fridovich, 1978;Forsberg et al, 2001). Copper is also necessary in the diet to prevent inflammation (Denko, 1979) and emphysema in animal models (O'Dell et al, 1978), as well as reducing the adverse effects of maternal nicotine exposure on lung development in rats (Maritz & Windvogel, 2003), and so may also have a protective effect against COPD.…”

Section: Introductionmentioning

confidence: 99%

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Lung function and blood levels of copper, selenium, vitamin C and vitamin E in the general population

et al. 2005

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Background: Increased dietary intake of antioxidants has been associated with higher lung function, but few studies have used biological markers of antioxidant intake. Objective: This study aimed to determine if antioxidant status, as measured by blood levels, influences lung function. Design: Using a random subsample of 479 participants, aged 18-65 y old, from a larger cross-sectional observational study, the association of forced expiratory volume in 1 s (FEV 1 ) with plasma copper, vitamin C, vitamin E and serum selenium was assessed. Results: An s.d. increase in blood copper level was associated with a difference in FEV 1 of À48 ml (95% confidence intervals: À95, À2 ml, P ¼ 0.04), vitamin C þ 49 ml ( þ 4, þ 94, P ¼ 0.03), vitamin E À15 ml (À62, þ 32, P ¼ 0.53) and selenium þ 52 ml ( þ 7, þ 96, P ¼ 0.02). The sizes of association were not appreciably altered in a mutually adjusted model. Conclusions: Higher levels of serum vitamin C and selenium appear to be associated with higher FEV 1 . The association between higher serum copper and lower FEV 1 requires further study in view of the ubiquitous exposure to this mineral. Sponsorship: National Asthma Campaign and British Lung Foundation.

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Section: Coppermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lung function and blood levels of copper, selenium, vitamin C and vitamin E in the general population

et al. 2005

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“…Under an ideal scenario, the MITO-Porter encapsulating CoQ10 reaches the liver tissue via systemic injection, and the carrier is then internalized into hepatocytes via macropinocytosis. In the cytosol, the carrier delivers Reactive oxygen species (ROS) are mainly produced in the mitochondrial respiratory chain, and are associated with a variety of diseases including I/R injury, neurodegenerative diseases, tumor metastasis, metabolic syndrome and aging [5,[14][15][16][17][18]. Thus, a therapeutic strategy for the mitochondrial delivery of antioxidant chemicals could be useful for the treatment of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Yamada

Nakamura

Abe

et al. 2015

Journal of Controlled Release

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We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q10 (CoQ10), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ10 in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ10-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ10-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ10-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria.Finally, we applied the optimized CoQ10-MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ10-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ10 via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies.

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“…These pathways play a vital role in maintaining genetic integrity. The ability of an individual to prevent and repair damage is genetically determined and is the result of combinations of multiple genes that may display subtle differences in their activity (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Genes Involved in Homologous Recombination Repair Interact to Increase the Risk of Developing Acute Myeloid Leukemia

Seedhouse

Faulkner

Ashraf

et al. 2004

Clinical Cancer Research

150

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Purpose: Double-strand break repair via homologous recombination is essential in maintaining genetic integrity. RAD51 and XRCC3 are involved in the repair of DNA by this pathway, and polymorphisms have been identified in both the RAD51 (RAD51-G135C) and XRCC3 (XRCC3-Thr241Met) genes. The object of this study was to examine whether these polymorphisms may modulate susceptibility to the development of acute myeloid leukemia (AML), a disease that is characterized by genetic instability.Experimental Design: We studied the distribution of polymorphisms in RAD51 and XRCC3 in 216 cases of de novo AML, 51 cases of therapy-related AML (t-AML), and 186 control subjects using PCR followed by restriction enzyme digestion. The polymorphic deletion of the detoxification gene glutathione S-transferase M1 (GSTM1) was also examined by PCR.Results: The risk of the development of AML was found to be significantly increased when both variant RAD51-135C and XRCC3-241Met alleles are present [odds ratio (OR), 3.77; 95% confidence interval (CI), 1.39 -10.24], whereas the risk of t-AML development is even higher (OR, 8.11; 95% CI, 2.22-29.68), presumably because of the large genotoxic insult these patients receive after their exposure to radiotherapy or chemotherapy. If we further divide the AML group into patients in which the burden of DNA damage is increased, because of the deletion of the GSTM1 gene, the risk of development of AML is further increased (OR, 15.26; 95% CI, 1.83-127.27). Conclusions:These results strongly suggest that DNA double-strand breaks and their repair are important in the pathogenesis of both de novo and t-AML.

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Oxidative Stress, Human Genetic Variation, and Disease

Cited by 269 publications

References 126 publications

Lung function and blood levels of copper, selenium, vitamin C and vitamin E in the general population

Lung function and blood levels of copper, selenium, vitamin C and vitamin E in the general population

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Polymorphisms in Genes Involved in Homologous Recombination Repair Interact to Increase the Risk of Developing Acute Myeloid Leukemia

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