Publications

DNA Damage by Free Radicals

Iron and atherosclerosis: Lessons learned from rabbits relevant to human disease

Different Patterns of Oxidized Lipid Products in Plasma and Urine of Dengue Fever, Stroke, and Parkinson's Disease Patients: Cautions in the Use of Biomarkers of Oxidative Stress

Many products of lipid oxidation have been associated with human diseases. These include F2 -isoprostanes (F2-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), and cholesterol oxidation products (COPs). Here we present measurements of F2-IsoPs, HETEs, COPs, and arachidonate in single plasma samples of patients with acute (dengue fever and ischemic stroke) and chronic (Parkinson's) diseases, and in age-matched study controls. Urine samples were collected for F2-IsoPs analysis. Our analysis demonstrated elevated F2-IsoPs levels in ischemic stroke, HETEs in Parkinson's disease, dengue fever, and ischemic stroke, and COPs in Parkinson's disease and dengue fever patients, as compared with those in age-matched study controls. Strong but complex correlations were observed between levels of certain oxidized lipid products and age. The relations between various oxidized lipids and dengue fever, stroke, and Parkinson's disease are discussed in relation to the selection and application of biomarkers of oxidative lipid damage, in particular the need for corrections for age and lipid levels.

Chemiluminescence. Principles and applications in biology and medicine

This monographin the Springer Series in Molecular Biology is directed at research workers including graduate students in the fields of organelle and bacterial bioenergetics, particularly in the area of electron transport.In this area, it contains a large amount of detailed data and information through 1985-86.Because cytochrome c is the redox protein that has been most thoroughly investigated, a thorough and general review of this subject is important, and the book is a valuable reference source.The presentation is written in the style of a review article and assumes a basic knowledge of the thermodynamics of oxidationreduction and the chemiosmotic hypothesis.Particularly valuable are discussions and summaries of the pathways of electron transport in chemolithotrophic bacteria, as well as those involved in nitrate and sulfate respiration, and denitrification.These

HPLC of small molecules, a practical approach

Antioxidants in Nutrition, Health, and Disease

In recent years, there has been an explosion of interest about the use of `antioxidant' nutritional supplements. Do they really defend the body against diseases? Should we all be taking vitamin E, vitamin C, or more of certain polyunsaturated fats? Written by two leading experts in the field of free radicals in biology and medicine, this book unravels the confusion caused by many nutrition-related claims, and clarifies the situation over whether maintaining high intakes of vitamins, minerals, and other food consituents really does help protect against life-threatening diseases.

Thermodynamic analysis of mitochondrial DNA breakpoints reveals mechanistic details of deletion mutagenesis

Abstract Broad evidence support double-strand breaks (DSBs) as initiators of mitochondrial DNA (mtDNA) deletion mutations. But the mechanism of DSB-induced deletions, including the DSB repair pathway(s) involved, remains to be established. Here, we used DNA hybridization thermodynamics to analyze misalignment lengths surrounding deletion breakpoints. Our analysis of 9,655 previously reported mammalian mtDNA deletions and 1,307 novel Caenorhabditis elegans mtDNA deletions, indicates a significant role of 0–25bp misalignments, supporting the role of erroneous non-homologous and micro-homology dependent DSB repair in deletion formation. Based on these insights we propose that DSB-induced mtDNA deletions occur via the misjoining of DSB ends and/or strand invasion of open mtDNA regions by DSB ends.

Clonal expansion of mitochondrial DNA deletions is a private mechanism of ageing in long-lived animals

Summary Disruption of mitochondrial metabolism and loss of mitochondrial DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms of ageing (López-Otín et al. 2013). Human ageing is associated with loss in skeletal muscle mass and function (Sarcopenia), contributing significantly to morbidity and mortality. Muscle ageing is associated with loss of mtDNA integrity. In humans, clonally expanded mtDNA deletions co-localize with sites of fiber-breakage and atrophy in skeletal muscle. mtDNA deletions may therefore play an important, possibly causal role in sarcopenia. The nematode Caenorhabditis elegans also exhibits age-dependent decline in mitochondrial function and a form of sarcopenia. However, it is unclear if mtDNA deletions play a role in C. elegans ageing. Here we report identification of 266 novel mtDNA deletions in ageing nematodes. Analysis of the mtDNA mutation spectrum and quantification of mutation burden indicates that (1) mtDNA deletions in nematode is extremely rare, (2) there is no significant age-dependent increase in mtDNA deletions and (3) there is little evidence for clonal expansion driving mtDNA deletion dynamics. Thus, mtDNA deletions are unlikely to drive the age-dependent functional decline commonly observed in C. elegans . Computational modelling of mtDNA dynamics in C. elegans indicates that the lifespan of short-lived animals such as C. elegans is likely too short to allow for significant clonal expansion of mtDNA deletions. Together, these findings suggest that clonal expansion of mtDNA deletions is likely a private mechanism of ageing predominantly relevant in long-lived animals such as humans and rhesus monkey and possibly in rodents.

Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation

Exposure of human plasma to gas-phase (but not to whole) cigarette smoke (CS) produces oxidative damage to lipids [Frei, Forte, Ames & Cross (1991) Biochem. J. 277, 133-138], which is prevented by ascorbic acid. The ability of CS to induce protein damage was measured by the carbonyl assay and by loss of enzyme activity and protein -SH groups. Both whole and gas-phase CS caused formation of carbonyls in human plasma, which was partially inhibited by GSH but not by ascorbic acid or metal-ion-chelating agents. Isolated albumin exposed to CS showed much faster carbonyl formation (per unit protein) than did whole plasma; damage to isolated albumin was partially prevented by chelating agents. Isolated creatine kinase (CK) lost activity upon exposure to CS much faster than did CK in plasma. Direct addition to plasma of mixtures of some or all of the aldehydes reported to be present in CS caused protein carbonyl formation and inactivation of CK, but neither occurred to the extent produced by CS exposure.

Evidence for nitric oxide‐mediated oxidative damage in chronic inflammation Nitrotyrosine in serum and synovial fluid from rheumatoid patients

Reaction of nitric oxide (NO • ) with superoxide radical generates peroxynitrite, which can decompose to products that nitrate aromatic amino acids. Such nitro‐aromatics may be ‘markers’ of NO • ‐dependent oxidative damage. Blood serum and synovial fluid from patients with the inflammatory joint disease rheumatoid arthritis contain 3‐nitrotyrosine. By contrast, body fluids from normal subjects and patients with osteoarthritis contain no detectable 3‐nitrotyrosine; much lower levels were found in serum from patients in the early stages of rheumatoid arthritis. This is evidence that NO • plays a role in joint damage in rheumatoid arthritis.

Action of lead(II) and aluminium(III) ions on iron-stimulated lipid peroxidation in liposomes, erythrocytes and rat liver microsomal fractions

Lead (Pb2+) ions accelerate the lipid peroxidation observed when Fe2+ ions are added to phospholipid liposomes at pH 5.5 or pH 7.4, although Pb2+ ions alone do not induce any peroxidation. Similarly, aluminium (A13+) ions increase Fe2+-dependent liposomal peroxidation at pH 5.5. Both Pb2+ and A13+ accelerate the peroxidation of erythrocytes induced by high concentrations of H2O2 in the presence of azide, and they also increase the peroxidation that occurs when Fe2+ or Fe2+-ADP is added to rat liver microsomes at pH 7.4. It is proposed that increased lipid peroxidation may contribute to the toxic actions of Pb2+ in humans.

The resistance of transferrin, lactoferrin and caeruloplasmin to oxidative damage

Correspondence| November 15 1988 The resistance of transferrin, lactoferrin and caeruloplasmin to oxidative damage B Halliwell; B Halliwell Search for other works by this author on: This Site PubMed Google Scholar O I Aruoma; O I Aruoma Search for other works by this author on: This Site PubMed Google Scholar M Wasil; M Wasil Search for other works by this author on: This Site PubMed Google Scholar J M Gutteridge J M Gutteridge Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1988) 256 (1): 311–312. https://doi.org/10.1042/bj2560311a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation B Halliwell, O I Aruoma, M Wasil, J M Gutteridge; The resistance of transferrin, lactoferrin and caeruloplasmin to oxidative damage. Biochem J 15 November 1988; 256 (1): 311–312. doi: https://doi.org/10.1042/bj2560311a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1988 London: The Biochemical Society1988 Article PDF first page preview Close Modal You do not currently have access to this content.

Superoxide‐dependent formation of hydroxyl radicals in the presence of iron chelates

No abstract is provided for this article.

DNA base damage in mammalian chromatin by hydrogen peroxide/ferric and cupric ions

Effect of the hydrophilic α-tocopherol analog MDL 74,405 on detection of hydroxyl radicals in stunned myocardium in dogs

Oxygen free radicals and iron in relation to biology and medicine: Some problems and concepts

No abstract is provided for this article.

Free radicals and cardiovascular disease

Abstract Coronary heart disease is a major cause of death in the USA and Europe. A heart attack (myocardial infarction) is usually the consequence of two events—the narrowing of coronary arteries by atherosclerosis (Figure 1) and the formation of a blood clot (thrombus) in a narrowed artery, which blocks it completely and renders a portion of the heart muscle ischaemic (lacking inO2). Atherosclerosis of arteries in the brain also predisposes to stroke. There have been many speculations that dietary intakes of polyunsaturated fatty acids, cholesterol, antioxidant nutrients, iron, copper, and selenium affect the development of atherosclerosis. The purpose of this chapter is to review what is, and is not, actually known about this complex area.

Modulation of the peroxynitrite-scavenging activity of antioxidants by physiologic concentrations of bicarbonate.