No abstract is provided for this article.
No abstract is provided for this article.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSuperoxide dismutase activities of an iron porphyrin and other iron complexesRobert F. Pasternack and Barry HalliwellCite this: J. Am. Chem. Soc. 1979, 101, 4, 1026–1031Publication Date (Print):February 1, 1979Publication History Published online1 May 2002Published inissue 1 February 1979https://doi.org/10.1021/ja00498a038RIGHTS & PERMISSIONSArticle Views464Altmetric-Citations146LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (729 KB) Get e-Alertsclose Get e-Alerts
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Abstract This chapter reviews various theories of ageing, with a particular focus on the free-radical theory of ageing (cumulative oxidative damage by reactive species [RS] causes ageing) and the evidence supporting and challenging it. The mechanisms behind how genes (e.g. in yeast, C. elegans, and human progeroid syndromes) influence ageing are discussed, as is the role of telomeres and telomerase. The mechanisms by which caloric restriction can increase lifespan are discussed, especially the role of sirtuins and mTOR. How lifestyle (diet, exercise etc.) modulate ageing and age-related disease is also discussed. We explore whether production of RS and levels of oxidative damage in vivo increase with age (including a discussion of which proteins are special targets of damage), whether antioxidant levels (especially those of GSH) and repair or clearance mechanisms (e.g. DNA repair, the proteasome, autophagy) decline with age, and if increased antioxidant levels (administered directly, or raised by transgenic manipulations) can affect ageing. The roles of RS generated by mitochondria, and of deletions in mitochondrial DNA in modulating ageing are explored. The second part of the chapter reviews the role of antioxidants in treating disease, both agents specifically designed to decrease oxidative damage, as well as drugs targeting other mechanisms that may also have antioxidant activity (e.g. sulphasalazine, statins). Examples of the former reviewed in detail include catalase, SODs, SOD mimetics (including managanese chelates), mitochondrially targeted antioxidants, edaravone, Ebselen, nitrones, nitroxides, thiols (GSH, N -acetylcysteine, lipoate etc.), iron ion chelators, Nrf2 activators, and inhibitors of NADPH oxidases, myeloperoxidase, and xanthine oxidase.
This letter discusses the various artefacts that can arise when ascorbate or other redox-active compounds are added to cell culture media.
No abstract is provided for this article.
The neurodegenerative diseases that afflict humans affect different part of the nervous system and have different symptoms and prognoses, yet they have certain things in common. One of them is defects in the clearance of abnormal or other "unwanted" proteins, particularly affecting the proteasome system. In this review, I advance two concepts: (a) that defects in protein clearance can be a fundamental cause of neurodegeneration, and (b) that because proteasome inhibitors are widespread in nature, their ingestion may contribute to "spontaneous" neurodegeneration.
A bstract : This article reviews the roles and interactions of iron, atherosclerosis, and neurodegeneration. It highlights the importance of cholesterol in promoting iron‐dependent oxidative damage. An intriguing possibility is that hypercholesterolemia can increase brain iron load and both the aggregation of beta‐amyloid and the ability of iron on plaques to catalyze oxidative damage. This could explain why hypercholesterolemia is a risk factor for Alzheimer's disease. Further work is necessary to study the mechanism of increased iron transport across the blood brain barrier in atherosclerosis.
Abstract This chapter describes the fundamental principles behind the detection and measurement of reactive species (RS) in vivo, as well as the quantification of the damage that they can do to biomolecules (oxidative damage). The use of electron spin resonance (ESR) is described in detail, with a particular focus on spin traps such as PBN, DMPO and DEPMPO, TEMP, TEMPD, and POBN, and the technique of immuno-spin trapping. The detection of hydroxyl radicals by spin trapping, aromatic hydroxylation, deoxyribose degradation, and other techniques is presented, as is the detection of superoxide and nitric oxide by ESR and other techniques, both direct and indirect (e.g. Griess reaction). Peroxynitrite measurement is described, as is that of singlet O2 (using fluorescent probes, spin traps, scavengers and quenchers, monomol and dimol light emission, and deuterium oxide). The measurement of cellular redox state and peroxide levels is explained in detail, especially the use of roGFPs, cpYFP, Amplex red, and Hyper or boronate-based H2O2 detectors. Essential points to be considered in the use of DCFHDA and other ‘ROS probes’ (luminol, lucigenin, L-012, HPF, APF, dihydrorhodamine, dihydroethidium) are presented in detail. Biomarkers of oxidative damage to bilirubin (biopyrrins) and urate (allantoin) are presented. The techniques used to measure oxidative damage to DNA (strand breaks, 8-hydroxyguanine, formamidopyrimidines), lipids (peroxides, conjugated dienes, loss of PUFAs, TBA test, aldehydes, isofurans, isoprostanes), and proteins (carbonyls, oxidation products of specific amino acid residues) are discussed. Finally, the value and limitations of ‘total antioxidant capacity’ determinations in food and body fluids are presented.
Peroxynitrite is a highly reactive species, generated from Superoxide and nitric oxide. Some effects of peroxynitrite are ascribed to the molecule itself, but decomposition products of the protonated form, peroxynitrous acid, may account for much of its reactivity in biological systems. Suggested products include highly‐reactive hydroxyl radicals, but thermodynamic calculations have been used to claim that free hydroxyl radicals cannot be formed from peroxynitrite. We utilized aromatic hydroxylation of phenylalanine as a specific detector of hydroxyl radicals, and found that incubation of phenylalanine with peroxynitrite leads to a small amount of p ‐, m ‐ and o ‐tyrosine, specific products of attack by this radical. Products of nitration of phenylalanine and tyrosine were also detected, as was dityrosine. Peroxynitrite decomposition generates several reactive species, including some that can nitrate aromatic rings. Formation of nitro‐aromatic compounds may be a useful marker of peroxynitrite generation in biological systems.
Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause. This article first reviews what is meant by the terms free radical, RS, antioxidant, oxidative damage and oxidative stress. It then critically examines methods used to trap RS, including spin trapping and aromatic hydroxylation, with a particular emphasis on those methods applicable to human studies. Methods used to measure oxidative damage to DNA, lipids and proteins and methods used to detect RS in cell culture, especially the various fluorescent "probes" of RS, are also critically reviewed. The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results.
