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

Reznick, Abraham Z.; Cross, Carroll E.; Hu, Miao‐Lin; Suzuki, Yuichiro; Khwaja, Shamsuddin; Safadi, Asaad; Motchnik, Paul A.; Packer, Lester; Halliwell, Barry

doi:10.1042/bj2860607

Cited by 255 publications

(115 citation statements)

References 31 publications

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“…Another line of research focused on the possible role of CSborne aldehydes (such as acroline or acetaldehyde) which are known to mediate the CS-inflicted damage in other systems, such as on plasma proteins (Reznick et al, 1992). The addition of the biological thiol GSH (often recognised as the primordial antioxidant), intended to prevent aldehyde damage, substantially protected the cells in our system at all time points examined (Figures 7 -9).…”

Section: Discussionmentioning

confidence: 96%

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

2004

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Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy and accounts for 2 -4% of all new cancers. It is primarily induced by exposure to tobacco. The paradigm of cigarette smoke (CS)-induced OP cancer's pathogenesis is based on the assumption that a constant direct attack of various CS carcinogens causes widespread accumulating cellular and DNA aberrations in the OP mucosal cells, in turn eventually resulting in malignant transformation. However, there is never a direct contact between CS and the OP mucosa. Saliva, bathing the mucosa from the oral cavity to the larynx, always intervenes, and CS must first interact with saliva before it reaches the mucosa. The current study investigated the role of saliva in the pathogenesis of OP cancer. A synergistic effect of CS and saliva on oral cancer cells was demonstrated. This synergism is based on the reaction between redox active metals in saliva and low reactive free radicals in CS, which results in the production of highly active hydroxyl free radicals. Thus, when exposed to CS, salivary behavior is reversed and the saliva loses its antioxidant capacity and becomes a potent prooxidant milieu. The devastating role of CS-borne aldehydes was demonstrated as well. Based on these results and on our recent reports demonstrating that CS destroys various salivary components, including protective ones such as peroxidase, the most important salivary antioxidant enzyme, a comprehensive view of the pivotal role of saliva in the pathogenesis of CS-induced OP cancer is suggested. Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy, having a worldwide incidence of over 300 000 new cases each year and accounting for 2 -4% of all new cancers (Bross and Coombes, 1976;McGinnis and Foege, 1993;Collins et al, 1994;Ko et al, 1995;Piyathilake et al, 1995;Zheng et al, 1997;Nagler et al, 1999; Lippman and Hong, 2001). The commonly accepted paradigm for cigarette smoke (CS)-induced OP cancer pathogenesis is based on the assumption that a constant and direct attack of various CS carcinogens causes widespread accumulating cellular and DNA aberrations in the OP mucosa eventually leading to malignant transformation and cancer development. The CS-borne carcinogens are often thought to be free radicals. The process is initially expressed by dysplastic mucosal lesions which are then transformed into in situ carcinoma lesions, eventually resulting in fullblown infiltrating and metastasising OP cancer (Holleb et al, 1991). Chen et al (2002) demonstrated that chewing tobacco (areca quid) resulted in the formation of ROS in the oral cavity causing oxidative DNA damage to the surrounding tissues. Further support can be found in a report demonstrating that premalignant mucosal lesions and low-grade carcinomas express DNA aberrations following a pathway of exposure to free radicals (Sudb et al, 2001). Moreover, Bloching et al (2001) recently found increased genotoxic activity in the saliv...

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Section: Discussionmentioning

confidence: 96%

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

2004

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“…These include free radical generated prostaglandin isomers (isoprostanes), 4-hydroxy-2-nonenal (membrane lipid peroxidation product) or 4-hydroxy 2-nonenal modified proteins, malondialdehyde (endproduct of lipid peroxidation), malondialdehyde-modified proteins, protein-bound acrolein, free radical modified DNA, conjugate dienes (intermediate product of free radical damage) and protein carbonylation have all served as indices of peroxidative damage. As an alternative to these indirect methods, owing to the fact that the free radicals are paramagnetic, electron paramagnetic resonance spectroscopy combined with spin trapping has become an important tool to directly assess free radicals [3][4][5].…”

Section: Phases Of Lipid Peroxidationmentioning

confidence: 99%

Autoimmunity and oxidatively modified autoantigens

Kurien

Scofield

2008

Autoimmunity Reviews

240

194

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Oxidative damage mediated by reactive oxygen species results in the generation of deleterious byproducts. The oxidation process itself and the proteins modified by these molecules are important mediators of cell toxicity and disease pathogenesis. Aldehydic products, mainly the 4-hydroxy-2-alkenals, form adducts with proteins and make them highly immunogenic. Proteins modified in this manner have been shown to induce pathogenic antibodies in a variety of diseases including systemic lupus erythematosus (SLE), alcoholic liver disease, diabetes mellitus (DM) and rheumatoid arthritis (RA). 8-oxodeoxyguanine (oxidatively modified DNA) and low density lipoproteins (LDL) occur in SLE, a disease in which premature atherosclerosis is a serious problem. In addition, immunization with 4-hydroxy-2-nonenal (HNE) modified 60 kD Ro autoantigen induces an accelerated epitope spreading in an animal model of SLE. Advanced glycation end product (AGE) pentosidine and AGE modified IgG have been shown to correlate with RA disease activity. Oxidatively modified glutamic acid decarboxylase is important in type 1 DM, while autoantibodies against oxidized LDL are prevalent in Behcet's disease. The fragmentation of scleroderma specific autoantigens occurs as a result of oxidative modification and is thought to be responsible for the production of autoantibodies through the release of cryptic epitopes. The administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease, particularly on account of the overwhelming evidence for the involvement of oxidative damage in autoimmunity. However, this should be viewed in the light of disappointing results obtained with the use of antioxidants in cardiovascular disease. Keywordslupus; autoimmunity; epitopes; autoantibodies; antigens Free radicalsReactive oxygen species (ROS) are oxygen-based molecules possessing high chemical reactivity. These include free radicals (superoxide and hydroxyl radicals) and non-radical species (hydrogen peroxide) which can be produced even at basal conditions by a number of ways. Free radicals are active species containing atoms or molecules with one or more unpaired electrons occupying an outer orbital. They can arise either by the univalent pathway of oxygen

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“…Interestingly uric acid has almost no effect against hypochlorous acid. Further, if source of ROS is kept same but different targets of oxidative damage are examined, the results may be different, for example, when human plasma is exposed to gas phase smoke ascorbic acid inhibits the lipid peroxidation but not the protein [160,161]. Finally, the striking observation is that black currant and apple juice inhibited lipid peroxidation in human volunteers but promoted protein oxidation [162].…”

Section: Antioxidant Juggernautmentioning

confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

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The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

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

Cited by 255 publications

References 31 publications

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

Autoimmunity and oxidatively modified autoantigens

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

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