Down's syndrome: A pathology involving the lack of balance of reactive oxygen species

Kędziora, J; Bartosz, Grzegorz

doi:10.1016/0891-5849(88)90052-4

Cited by 119 publications

(56 citation statements)

References 107 publications

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“…The increased toxicity of a variety of superoxide-radicalforming compounds observed in a number of cell types overexpressing SOD [3][4][5] has been considered to result from elevated hydrogen peroxide (H 2 O 2 ) concentrations and subsequent oxidative damage following hydroxyl radical generation [6,7]. This enhanced toxicity is likely to become evident in particular when the capacity for en-zymatic inactivation of H 2 O 2 is limited, such as is the case in insulin-producing cells [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Also manganese SOD (MnSOD) overexpression proved to be an efficient principle to ameliorate the activation of nuclear factor kappa B (NF-κB) and inducible nitric oxide (NO) synthase after cytokine exposure in insulin-producing RINm5F cells in the early phase of cytokine signalling [11]. In the light of these data the role of MnSOD in the toxicity of reactive oxygen species (ROS) and cytokines deserves specific consideration, as various studies in different cell types have reported a higher susceptibility to ROS rather than a protection [3][4][5]. This raises the question about the functional role of MnSOD in insulin-producing cells under the physiological situation of low-activity levels of H 2 O 2 -inactivating enzymes.…”

Section: Introductionmentioning

confidence: 99%

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Importance of mitochondrial superoxide dismutase expression in insulin-producing cells for the toxicity of reactive oxygen species and proinflammatory cytokines

et al. 2005

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Aims/hypothesis: Free radicals generated in mitochondria play a crucial role in the toxic effects of cytokines upon insulin-producing cells. This study therefore investigated the role of manganese superoxide dismutase (MnSOD) in cytokine-mediated toxicity in insulin-producing cells. Methods: MnSOD was either stably overexpressed (MnSODsense) or stably suppressed (MnSODantisense) in insulin-producing RINm5F cells. Cell viability was quantified after incubation with different chemical reactive oxygen species (ROS) generators and with cytokines (IL-1β alone or a mixture of IL-1β, TNF-α and IFN-γ). Additionally, cell proliferation and endogenous MnSOD protein expression were determined after exposure to cytokines. Results: After incubation with hydrogen peroxide (H 2 O 2 ) or hypoxanthine/xanthine oxidase no significant differences were observed in viability between control and MnSOD sense or MnSODantisense clones. MnSOD overexpression reduced the viability of MnSODsense cells after exposure to the intracellular ROS generator menadione compared with control and MnSODantisense cells. MnSODsense cells also showed the highest susceptibility to cytokine toxicity with more than 75% loss of viability and a significant reduction of the proliferation rate after 72 h of incubation with a cytokine mixture. In comparison with control cells (67% viability loss), the reduction of viability in MnSODantisense cells was lower (50%), indicating a sensitising role of MnSOD in the progression of cytokine toxicity. The cell proliferation rate decreased in parallel to the reduction of cell viability. The MnSOD expression level after exposure to cytokines was also significantly lower in Mn SODantisense cells than in control or MnSODsense cells. Conclusions/interpretation: The increase of the mitochondrial imbalance between the superoxide-and the H 2 O 2 -inactivating enzyme activities corresponds with a greater susceptibility to cytokines. Thus optimal antioxidative strategies to protect insulin-producing cells against cytokine toxicity may comprise a combined overexpression of H 2 O 2 -inactivating enzymes or suppression of MnSOD activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Importance of mitochondrial superoxide dismutase expression in insulin-producing cells for the toxicity of reactive oxygen species and proinflammatory cytokines

et al. 2005

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“…A clue to the pathogenesis of dementia was the finding that Down's syndrome subjects, who exhibit chromosome-21 trisomy, possess an extra copy of the Cu-Zn SOD gene, suggesting perturbation of the redox balance (Kedziora & Bartosz, 1988). Evidence of redox changes in AD brains is indicated by the increased 0-stimulated peroxidation (Gotz et al 1992), accumulation of lipofuscin (Dowson, 1989), and oxidatively-modified dysfunctional glutamine synthetase (EC 6.3.1.2; Smith cr al.…”

Section: A L Z H E I M E R ' S D I S E a S E A N D F R E E R A D I C mentioning

confidence: 99%

Nutrient and toxin interactions in neurodegenerative disease

Evans

1994

Proc. Nutr. Soc.

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The brain is the most complex organ of the body. Its effective function is dependent on its unique anatomical structure and neuronal cell morphology, together with the efficient coordination of its metabolic and physiological processes. The degenerative diseases of the brain, for example Huntington's, Parkinson's and Alzheimer's disease (AD), are generally characterized by an associated loss of functional neurones, with accompanying motor, memory and cognitive deficits.In the case of familial amyotrophic lateral sclerosis (ALS; Deng et al. 1993), Huntington's disease, early-onset dementia of familial AD (Martin, 1993), and the prion diseases (the spongiform encephalopathies, i.e. Creutzfeldt-Jacob disease and the Gerstmann-Straussler-Scheinker syndrome; Prusiner, 1991), a genetic aetiology has been demonstrated. The larger number of so-called sporadic cases of AD which occur in the 8th and 9th decades of life, suggests that environmental factors are also operative. Even so, recent findings concerning apolipoprotein E €4 allele indicate genetic polymorphisms are significant risk factors in the development of late-onset AD as well . Hence, senile dementia of the Alzheimer type, the most common of the neurodegenerative diseases, appears to be of multifactorial origin, presenting a complex interplay of genetic, environmental, and age-related factors (Calne et al. 1986). B R A I N R E S E A R C HUndertaking studies into the toxicological and nutritional aspects of neurodegeneration, poses a range of ethical, organizational, technical and financial, challenges. Since there is no laboratory test for AD and the definitive diagnosis is dependent on postmortem identification and quantification of the pathognomic intracellular neurofibrillary tangles and extracellular senile plaques within the brain, epidemiological and clinical investigations into AD are extremely problematic. However, tests for cognitive function, and development of new in vivo imaging techniques, namely magnetic resonance imaging and positron emission topography scans, do permit a degree of clinical assessment.The inherent difficulty of research into the brain is compounded not only by the diverse range of neuronal and glial cell types and the complexity of the integrated neural network, but also by the properties of redundancy and plasticity exhibited by the brain. Brain damage related to degenerative change may not become apparent until the loss of neurones reaches a particular threshold level. Hence, cognitive deficits appearing in later life may not be directly caused by senility or the ageing process itself, but may be the result of developmental deficits or toxic damage which has occurred several decades earlier. Studies indicating the major significance of pre-or early postnatal nutrition to infant brain development (Lucas, 1993) and the subsequent development of disease in adult life (Barker et al. 1989), are of particular importance in relation to the nonreplicative nature of neuronal cells. While the significance of proper nutrition in early b...

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“…The activity of superoxide dismutase (SOD) -a key enzyme in the metabolism of oxygen-derived free radicals -is increased in DS (see below). This increase in SOD activity may alter the normal steady state equilibrium of reactive oxygen species leading to oxidative injury in DS 4,5 .…”

Section: Oxidative Stress In Dsmentioning

confidence: 99%

Nutritional supplementation in Down syndrome: theoretical considerations and current status

Ani

Grantham‐McGregor

Muller

2000

Develop Med Child Neuro

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Down's syndrome: A pathology involving the lack of balance of reactive oxygen species

Cited by 119 publications

References 107 publications

Importance of mitochondrial superoxide dismutase expression in insulin-producing cells for the toxicity of reactive oxygen species and proinflammatory cytokines

Importance of mitochondrial superoxide dismutase expression in insulin-producing cells for the toxicity of reactive oxygen species and proinflammatory cytokines

Nutrient and toxin interactions in neurodegenerative disease

Nutritional supplementation in Down syndrome: theoretical considerations and current status

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