Oxidative stress

About: Oxidative stress is a research topic. Over the lifetime, 86513 publications have been published within this topic receiving 3845790 citations. The topic is also known as: oxydative stress.

Oxidative Alterations in Alzheimer's Disease

Abstract: There is increasing evidence that free radical damage to brain lipids, carbohydrates, proteins, and DNA is involved in neuron death in neurodegenerative disorders. The largest number of studies have been performed in Alzheimer's disease (AD) where there is considerable support for the oxidative stress hypothesis in the pathogenesis of neuron degeneration. In autopsied brain there is an increase in lipid peroxidation, a decline in polyunsaturated fatty acids (PUFA) and an increase in 4-hydroxynonenal (HNE), a neurotoxic aldehyde product of PUFA oxidation. Increased protein oxidation and a marked decline in oxidative-sensitive enzymes, glutamine synthetase and creatinine kinase, are found in the brain in AD. Increased DNA oxidation, especially 8-hydroxy-2′-deoxyguanosine (8-OHdG) is present in the brain in AD. Immunohistochemical studies show the presence of oxidative stress products in neurofibrillary tangles and senile plaques in AD. Markers of lipid peroxidation (HNE, isoprostanes) and DNA (8-OHdG) are increased in CSF in AD. In addition, inflammatory response markers (the complement cascade, cytokines, acute phase reactants and proteases) are present in the brain in AD. These findings, coupled with epidemiologic studies showing that anti-inflammatory agents slow the progression or delay the onset of AD, suggest that inflammation plays a role in AD. Overall these studies indicate that oxidative stress and the inflammatory cascade, working in concert, are important in the pathogenetic cascade of neurodegeneration in AD, suggesting that therapeutic efforts aimed at both of these mechanisms may be beneficial.

Dissection of Oxidative Stress Tolerance Using Transgenic Plants.

Abstract: Environmental stress is the major limiting factor in plant productivity. Much of the injury to plants caused by stress exposure is associated with oxidative damage at the cellular level. Widespread losses of forests and crops due to ozone pollution provide a highly visible example of oxidative stress (see Tingey et al., 1993, for a review), but less obvious losses caused by oxidative damage associated with periods of cold or drought also take their toll in the accumulation of incremental setbacks during a growing season. The role of ROIs in plant stress damage is indicated by the increased production of ROIs and the increased oxidative damage in tissues during stress. In plants, the highly energetic reactions of photosynthesis and an abundant oxygen supply make the chloroplast a particularly rich source of ROIs. High light intensity can lead to excess reduction of PSI so that CO2 fixation cannot keep pace and NADP+ pools are reduced. Under these conditions, 02 can compete for electrons from PSI, leading to the generation of ROIs through the Mehler reaction. When CO2 fixation is limited by environmental conditions such as cold temperatures or low CO2 availability (closed stomata), excess PSI reduction and increased ROI production can occur even at moderate light intensities. Efficient removal of ROIs from chloroplasts is critical, since H202 concentrations as low as 10 ptM can inhibit photosynthesis by 50% (Kaiser, 1979). Although the toxicity of *?2and H202 themselves is relatively low, their metal-dependent conversion to the highly toxic -OH via the Haber-Weiss reaction is thought to be responsible for the majority of the biological damage associated with these molecules. Antioxidant systems of plant chloroplasts include enzymes such as SOD and APX, and nonenzymatic components such as ascorbic acid and glutathione. The proposed ROI scavenging pathway of chloroplasts is shown in Figure 1 (Asada, 1994). Superoxide radicals are produced by the reduction of molecular oxygen at PSI via the Mehler reaction. This ?2- is rapidly dismuted to H202 by SOD that is associated with the thylakoid. The H202 produced is

Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate

Abstract: Increasing evidence suggests that glutamate neurotoxicity is partly mediated by reactive oxygen species, formed as a consequence of several processes, including arachidonic acid metabolism and nitric oxide production. Here we used an oxidation-sensitive indicator, dihydrorhodamine 123, in combination with confocal microscopy, to examine the hypothesis that electron transport by neuronal mitochondria may be an important source of glutamate-induced reactive oxygen species (ROS). Exposure to NMDA, but not kainate, ionomycin, or elevated potassium stimulated oxygen radical production in cultured murine cortical neurons, demonstrated by oxidation of nonfluorescent dihydrorhodamine 123 to fluorescent rhodamine 123. Electron paramagnetic resonance spectroscopy studies using 5,5-dimethyl-1- pyrroline-N-oxide (DMPO) as a radical-trapping agent, also showed production of ROS by cortical neurons after NMDA but not kainate exposure. NMDA-induced ROS production depended on extracellular Ca2+, and was not affected by inhibitors of nitric oxide synthase or arachidonic acid metabolism. The increased production of ROS was blocked by inhibitors of mitochondrial electron transport, rotenone or antimycin, and mimicked by the electron transport uncoupler, carbonyl cyanide p-trifluoromethoxyphenylhydrazone. These data support the possibility that NMDA receptor-mediated, Ca(2+)-dependent uncoupling of neuronal mitochondrial electron transport may contribute to the oxidative stress initiated by glutamate exposure.

Oxidative stress and antioxidative system in plants

Abstract: Free radicals and other active derivatives of oxygen are inevitable by-products of biological redox reactions. Reactive oxygen species inactivate enzymes and damage important cellular components. The increased production of toxic oxygen derivatives is considered to be a universal or common feature of stress conditions. Plant and other organisms have evolved a wide range of mechanisms to contend with this problem. The antioxidant defence system of the plant comprises a variety of antioxidant molecules and enzymes. The effects of the action of free radicals on membranes include the induction of lipid peroxidation and fatty acid de-esterification. Both ethylene biosynthesis and membrane breakdown, which appear to be closely linked, seem to involve free radicals, although the sequence of events generating these free radicals is still poorly understood. It is clear that the capacity and activity of the antioxidative defence system are important in limiting oxidative damage and in destroying active oxygen species that are produced in excess of those normally required for metabolism. Transgenic plants offered us a means by which to achieve complete understanding of the roles of the enzymes involved in protection against stress of many types, environmental and induced. Studies on transformed plants expressing increased activities of single enzymes of the antioxidative defence system indicate that it is possible to confer a degree of tolerance to stress by these means. The advent of plant transformation has placed within our grasp the possibility of engineering greater stress tolerance in plants by enhancements of the antioxidative defence system.

Mitochondria in the aetiology and pathogenesis of Parkinson's disease.

Abstract: Summary Several biochemical abnormalities have been described in the brains of patients with Parkinson's disease (PD), including oxidative stress and mitochondrial dysfunction. The identification of specific gene mutations that cause PD has reinforced the relevance of oxidative stress and mitochondrial dysfunction in the familial and the sporadic forms of the disease. The proteins that are associated with familial PD—PTEN-induced putative kinase 1 (PINK1), DJ-1, α-synuclein, leucine-rich repeat kinase 2, and, possibly, parkin—are either mitochondrial proteins or are associated with mitochondria, and all interface with the pathways of oxidative stress and free radical damage. Insights into the aetiology and pathogenesis of PD provide hope that drugs or cocktails of drugs that might successfully intervene in the pathogenesis and slow the progression of the disease can be derived from the study of the converging rather than diverging pathways to cell dysfunction and death.