Metal-catalyzed oxidative damage and oligomerization of the amyloid-β peptide of Alzheimer’s disease

The most common form of dementia in old age is Alzheimer’s disease (AD). The presence in the brain of senile plaque is the major pathological marker of AD. The plaques are primarily composed of aggregated amyloid-β peptide (Aβ). Aβ is a 40–42 amino acid peptide that is a proteolytic product derived from the β-amyloid precursor protein. The function of Aβ and the exact mechanism of Aβ aggregation and neurotoxicity are unclear. However, metal coordination by Aβ plays an important role in inducing aggregation and the generation of reactive oxygen species, which appears to be at least partially responsible for Aβ neurotoxicity. In this review we examine the role of copper and zinc ions in Aβ neurotoxicity, especially with regards to the generation of free radicals. We discuss the role of copper or zinc ions in oxidative damage and Aβ conformational changes and the relationship of these metals to AD.

CoQ10 conveys protection from oxidative stress in plasma but not skeletal muscle

Coenzyme Q10 (CoQ10) is commonly consumed as an antiaging supplement at doses of 30–210 mg/day. The aim of the study was to determine if CoQ10 alters markers of antioxidant status, oxidative damage, and gene expression in aging skeletal muscle. Female guinea pigs aged 26 months were supplemented for 6 weeks with CoQ10 at a human equivalent dose of 10 mg/kg/day. Body weight, plasma CoQ10 concentration, and WBC DNA abasic sites were measured at weeks 0, 2, 4, and 6 of the supplementation period. At the end of supplementation, concentrations of skeletal muscle CoQ10, glutathione, malondialdehyde, protein carbonyls, DNA abasic sites, activities of catalase and glutathione peroxidase, and the gene expression of cyctochrome c oxidase subunits were measured. Dietary supplementation with CoQ10 elevated plasma CoQ10 levels (pre 73 ± 3 nmol/L, post 581 ± 15 nmol/L, P < 0.05) and decreased abasic sites in WBC DNA (pre 16.8 ± 0.5 Ap/100000 bp, post 9.7 ± 0.4 Ap/100000 bp, P < 0.05). In contrast, all of the measures made in skeletal muscle were not different between groups (P > 0.05). These results indicate that dietary supplementation with CoQ10 at a dose of 10 mg/kg/day may be capable of increasing antioxidant protection and reducing oxidative damage in the plasma, but may have no effect in skeletal muscle.

From bivalves to birds : oxidative stress and longevity

1. The oxidative stress theory of ageing predicts that animals living longer will have less cumulative oxidative damage together with structural characteristics that make them more resistant to oxidative damage itself.
2. Although a general relationship between body size, metabolism and longevity does not exist in marine invertebrates, they are generally characterized by low rates of metabolism and reactive oxygen species (ROS) formation associated with lower antioxidant enzyme activities compared to vertebrates.
3. Birds and mammals have very similar size-affected metabolic rates and their metabolic intensity explains only some of the variation in maximum lifespan potential (MLSP).Within each class, smaller animals have higher rates of metabolism and ROS production and membranes that are more susceptible to oxidative damage and autocatalytic propagation of free radicals than larger ones.
4. Although the high variation in life-history strategies is accompanied by substantial variation in MLSP, there is a consistent positive correlation between rates of ROS formation and antioxidant levels among most animals examined so far for these traits. The consensus of these studies is that ROS and antioxidant levels are inversely related to MLSP.
5. The lack of a clear stoichiometric relation between variables contributing to oxidative stress limits our capacity to infer longevity consequences from measures of pro-oxidant or antioxidant status among or within species

Oxidative stress in psychiatric disorders : evidence base and therapeutic implications

Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage. This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications. A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Previews, and Cochrane databases, with a time-frame extending to September 2007. The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants. For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial. Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data. Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.

Consumption of a low glycaemic index diet in late life extends lifespan of Balb/c mice with differential effects on DNA damage

Background : Caloric restriction is known to extend the lifespan of all organisms in which it has been tested. Consequently, current research is investigating the role of various foods to improve health and lifespan. The role of various diets has received less attention however, and in some cases may have more capacity to improve health and longevity than specific foods alone. We examined the benefits to longevity of a low glycaemic index (GI) diet in aged Balb/c mice and examined markers of oxidative stress and subsequent effects on telomere dynamics.

Results : In an aged population of mice, a low GI diet extended average lifespan by 12%, improved glucose tolerance and had impressive effects on amelioration of oxidative damage to DNA in white blood cells. Telomere length in quadriceps muscle showed no improvement in the dieted group, nor was telomerase reactivated.

Conclusion : The beneficial effects of a low GI diet are evident from the current study and although the impact to telomere dynamics late in life is minimal, we expect that earlier intervention with a low GI diet would provide significant improvement in health and longevity with associated effects to telomere homeostasis.

The energetic and oxidative costs of reproduction in a free-ranging rodent

1. As understanding of the energetic costs of reproduction in birds and mammals continues to improve, oxidative stress is an increasingly cited example of a non-energetic cost of reproduction that may serve as a proximal physiological link underlying life-history trade-offs.

2. Here, we provide the first study to measure daily energy expenditure (DEE) and oxidative damage in a wild population. We measured both traits on eastern chipmunks (Tamias striatus) and assessed their relationships with age, reproductive status, litter size and environmental conditions.

3. We found that both physiological traits were correlated with environmental characteristics (e.g. temperature, seasons). DEE tended to increase with decreasing temperature, while oxidative damage was lower in spring, after a winter of torpor expression, than in autumn. We also found that DEE decreased with age, while oxidative damage was elevated in young individuals, reduced in animals of intermediate age and tended to increase at older age.

4. After controlling for age and environmental variables, we found that both female DEE and oxidative damage increased with litter size, although the latter increased weakly.

5. Our results corroborate findings from laboratory studies but highlight the importance of considering environmental conditions, age and reproductive status in broader analyses of the causes and consequences of physiological costs of reproduction in wild animals.

Associations between DNA damage, DNA base excision repair gene variability and Alzheimer's disease risk

BACKGROUND: Increased oxidative damage to DNA is one of the pathways involved in Alzheimer's disease (AD). Insufficient base excision repair (BER) is in part responsible for increased oxidative DNA damage. The aim of the present study was to assess the effect of polymorphic variants of BER-involved genes and the peripheral markers of DNA damage and repair in patients with AD. MATERIAL AND METHODS: Comet assays and TaqMan probes were used to assess DNA damage, BER efxFB01;ciency and polymorphic variants of 12 BER genes in blood samples from 105 AD patients and 130 controls. The DNA repair efficacy (DRE) was calculated according to a specific equation. RESULTS: The levels of endogenous and oxidative DNA damages were higher in AD patients than controls. The polymorphic variants of XRCC1 c.580C>T XRCC1 c.1196A>G and OGG1 c.977C>G are associated with increased DNA damage in AD. CONCLUSION: Our results show that oxidative stress and disturbances in DRE are particularly responsible for the elevated DNA lesions in AD. The results suggest that oxidative stress and disruption in DNA repair may contribute to increased DNA damage in AD patients and risk of this disease. In addition, disturbances in DRE may be associated with polymorphisms of OGG1 and XRCC1.

The molecular basis of copper homeostasis and copper-related disorders

Copper is an essential trace element that can be extremely toxic in excess due to the pro-oxidant activity of copper ions. Inherited disorders of copper transport, Menkes disease (copper deficiency), and Wilson disease (copper toxicosis) are caused by mutations of two closely related Cu transporting-ATPases, and demonstrate the essentiality and potential toxicity of copper. Other copper toxicosis conditions in humans and animals have been described, but are not well understood at a molecular level. Copper homeostatic mechanisms are being discovered. One such mechanism is copper-induced trafficking of the Cu-ATPases, which allows cells to provide copper to secreted cupro-proteins but also to efflux excess copper. Oxidative damage induced by copper may be involved in the pathogenesis of neurodegenerative conditions such as Alzheimer's disease, familial amyotrophic lateral sclerosis, and prion diseases.

植物CytP450和抗氧化酶对土壤菲、芘暴露的生态毒理响应

Maize (Zea mays L.) for the tested plants, meadow brown soil as the soil tested in order to microsomal cytochrome P450 content, superoxide dismutase (SOD), catalase (CAT) and peroxidase enzyme (POD) activity of indicators, the soil phenanthrene and pyrene in response to exposure to eco-toxicological studies. The results show that phenanthrene, pyrene exposure can cause detoxification of plant metabolism and antioxidant defense system of the stress response, caused varying degrees of detoxification of plant metabolism and changes in antioxidant capacity. P450 enzyme activity and low concentrations of phenanthrene and pyrene in a single - relevant exposure concentration (r = 0.834, P <0.01), and phenanthrene and pyrene exposure concentration was negatively correlated compound, saying that Ming Fei, pyrene compound exposed to lead detoxification metabolism of a reduced ability to detoxify the metabolism of plants have synergistic toxic effects; SOD activity and phenanthrene and pyrene in a single exposure concentration was negatively correlated, CAT activity and phenanthrene and pyrene in a single - exposure concentration was positively correlated, POD activity and water solubility of the Philippines positively correlated with the total concentration of pyrene in a negative correlation. SOD, CAT and POD activity and phenanthrene and pyrene were positively related to the concentration of compound exposure, saying that Ming Fei, pyrene complex degree of exposure to lead to reduced oxidative damage, oxidative damage of plants with antagonistic effects .

Chemistry and health of olive oil phenolics

The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, and certain types of cancer. The apparent health benefits have been partially attributed to the dietary consumption of virgin olive oil by Mediterranean populations. Most recent interest has focused on the biologically active phenolic compounds naturally present in virgin olive oils. Studies (human, animal, in vivo and in vitro) have shown that olive oil phenolics have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, and antimicrobial activity. Presumably, regular dietary consumption of virgin olive oil containing phenolic compounds manifests in health benefits associated with a Mediterranean diet. This paper summarizes current knowledge on the physiological effects of olive oil phenolics. Moreover, a number of factors have the ability to affect phenolic concentrations in virgin olive oil, so it is of great importance to understand these factors in order to preserve the essential health promoting benefits of olive oil phenolic compounds.