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.
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.
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.
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.
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No abstract is provided for this article.
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.
Oxidative Stress, Lipoproteins and Cardiovascular Dysfunction Edited by C. Rice-Evans and K.R. Bruckdorfer Portland Press Research Monograph VII, Portland Press London UKFree Radicals and Oxidative Stress: Environment, Drugs and Food Additives C. Rice-Evans, B. Halliwell, G.C. Hunt (Eds) Portland Press: London. 1995 pp. 276 ISBN 1855780690
: Reactive oxygen and nitrogen species, including free radicals, are produced in the human body in both health and disease. In health, they may arise as regulatory mechanisms, intercellular signaling species, or as bacteriocidal agents. Their production is normally controlled by the antioxidant defense mechanisms that include intracellular enzymes‐for example, glutathione peroxidase and superoxide dismutase‐and low molecular‐mass compounds such as vitamin E or ascorbic acid. Although repair mechanisms exist, some steady‐state basal oxidative damage occurs in all individuals. Oxidative stress arises when there is a marked imbalance between the production and removal of reactive oxygen and nitrogen species. This may originate from an overproduction of these substances or from a depletion in the antioxidant defenses. Certain drugs may induce oxidative stress by forming drug‐derived radicals that can not only deplete the antioxidant defenses but can also react directly with biomolecules. To be able to assess whether oxidative stress is occurring in a particular tissue, reliable biomarkers of oxidative damage are required. Since oxidative stress can damage all major biomolecules in vitro and probably in vivo , biomarkers for DNA, protein, and lipid damage are being developed which, when taken with an assessment of the antioxidant status of the individual, will allow evaluation of the involvement of oxidative stress in the etiology of disease and in the side effects of drugs. There is some evidence to suggest that free radical‐mediated damage may be involved in the ototoxicity of aminoglycosides and cisplatin derivatives. Whether this is a cause or consequence of the toxic insult to the sensory hair cells of the inner ear remains to be determined.
Primitive obligate anaerobes of the oxygen-free period had to either avoid or evolve to live with the high levels of solar radiation. Aerobic life processes utilize molecular oxygen for the controlled oxidation of carbon-containing molecules with the concomitant release of energy and the reduction of oxygen to water. Some samples of synovial fluid from rheumatoid patients show bleomycin-detectable iron in amounts correlated to disease severity. The serum of some patients with rheumatoid arthritis contains raised concentrations of ceruloplasmin, and this confers a greater ferroxidase-dependent antioxidant activity on the fluid. Serum and synovial fluid taken from patients with active rheumatoid arthritis tend to have lower antioxidant activities, compared to controls, when tested for their ability to inhibit copper-promoted lipid peroxidation. The antioxidant defenses of extracellular fluids appear to be primarily directed towards containing the reactivity of metal ions in the presence of reduced oxygen intermediates, rather than directly removing the oxygen intermediates themselves.
