Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous oxidative damage to proteins, lipids, and DNA is thought to be an important etiologic factor in aging and the development of chronic diseases such as cancer, atherosclerosis, and cataract formation. The pathology associated with these diseases is likely to occur only after the production of reactive oxygen species has exceeded the body's or cell's capacity to protect itself and effectively repair oxidative damage. Vitamin C, vitamin E, and beta-carotene, often referred to as "antioxidant vitamins," have been suggested to limit oxidative damage in humans, thereby lowering the risk of certain chronic diseases. However, epidemiological studies and clinical trials examining the efficacy of antioxidant vitamins, either individually or in combination, to affect disease outcome rarely address possible underlying mechanisms. Thus, in these studies it is often assumed that antioxidant vitamins act by lowering oxidative damage, but evidence in support of this contention is not provided. Therefore, in this review, we examine the scientific evidence that supplementation of humans with vitamin C, vitamin E, or beta-carotene lowers in vivo oxidative damage to lipids, proteins, or DNA based on the measurement of oxidative biomarkers, not disease outcome. With the only exception of supplemental vitamin E, and possibly vitamin C, being able to significantly lower lipid oxidative damage in both smokers and nonsmokers, the current evidence is insufficient to conclude that antioxidant vitamin supplementation materially reduces oxidative damage in humans.
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PMID:Can antioxidant vitamins materially reduce oxidative damage in humans? 1023 49

There has been a growing interest during recent years in the role of free radicals and lipid-peroxidation at tissue-level for the causation of cancer and other age-related diseases like atherosclerosis, rheumatoid arthritis, cataract etc. Free radicals and increased lipid peroxidation play a significant role for causation of human diseases by oxidative damage and functional degeneration of the tissues. Vitamin C, a well-known dietary antioxidant, and other enzymatic antioxidants like glutathione can protect the lipids of lipoproteins and other biomembranes against peroxidative damage by intercepting oxidants before they can attack the tissues. But cigarette smoking was found to affect the antioxidant protective action of Vitamin C, glutathione etc. A group of adult male smokers in this study were found to have lowered Vitamin 'C' & glutathione levels, but increased lipid-peroxide levels in their blood. Thus the increased pathogenicity of the smoking may also be due to indirect biochemical effect of enhanced oxidative stress by increased lipid-peroxidation and lowered Vitamin C & other antioxidants at tissue-level.
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PMID:Influence of cigarette smoking on Vitamin C, glutathione and lipid peroxidation status. 1038 2

It has been reported in the epidemiological literature that cataract, stroke, and atherosclerosis risk is reduced by 50% in people consuming one alcoholic drink per day. Peroxide has been implicated as a causative agent in cataractogenesis, and LDL oxidation appears to play a role in atherosclerosis. The antioxidant activity of alcohol was measured by: (i) use of a luminescent assay developed in our laboratory, confirmed as appropriate; (ii) electron spin resonance (ESR) spin-trapping; and (iii) copper-catalysed oxidation of LDL and VLDL from hamsters fed 6% ethanol in their drinking water. Ethanol reduced the luminescent counts/min from peroxide and superoxide. It significantly reduced the spin-trapped signal of hydroxyl radical, but not the superoxide signal. Other alcohols also showed large reductions in counts from hydrogen peroxide. Plasma from hamsters fed 6% ethanol had lower lipid peroxides and the oxidizability of LDL and VLDL was significantly reduced compared to controls. These data provide a possible explanation for the effect of beverages containing ethanol in the reduction of cataract and atherosclerosis risk observed in human population studies.
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PMID:Is ethanol an important antioxidant in alcoholic beverages associated with risk reduction of cataract and atherosclerosis? 1049 11

The use of plants is as old as the mankind. Natural products are cheap and claimed to be safe. They are also suitable raw material for production of new synthetic agents. Rosemary (Rosmarinus officinalis Linn.) is a common household plant grown in many parts of the world. It is used for flavouring food, a beverage drink, as well as in cosmetics; in folk.medicine it is used as an antispasmodic in renal colic and dysmenorrhoea, in relieving respiratory disorders and to stimulate growth of hair. Extract of rosemary relaxes smooth muscles of trachea and intestine, and has choleretic, hepatoprotective and antitumerogenic activity. The most important constituents of rosemary are caffeic acid and its derivatives such as rosmarinic acid. These compounds have antioxidant effect. The phenolic compound, rosmarinic acid, obtains one of its phenolic rings from phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl-lactic acid. Relatively large-scale production of rosmarinic acid can be obtained from the cell culture of Coleus blumei Benth when supplied exogenously with phenylalanine and tyrosine. Rosmarinic acid is well absorbed from gastrointestinal tract and from the skin. It increases the production of prostaglandin E2 and reduces the production of leukotriene B4 in human polymorphonuclear leucocytes, and inhibits the complement system. It is concluded that rosemary and its constituents especially caffeic acid derivatives such as rosmarinic acid have a therapeutic potential in treatment or prevention of bronchial asthma, spasmogenic disorders, peptic ulcer, inflammatory diseases, hepatotoxicity, atherosclerosis, ischaemic heart disease, cataract, cancer and poor sperm motility.
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PMID:Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. 1064 Nov 30

Protein-bound 3,4-dihydroxyphenylalanine (DOPA) can be generated in mammalian cells by both controlled enzymatic pathways, and by uncontrolled radical reactions. Protein-bound DOPA (PB-DOPA) has reducing activity and the capacity to inflict secondary damage on other important biomolecules such as DNA. This may be mediated through replenishment of transition metals or from catechol-quinone-catechol redox cycles in the presence of cellular components such as ascorbate or cysteine, resulting in amplification of radical damaging events. The generation of PB-DOPA confers on protein the ability to chelate transition metals generating protein 'oxychelates'; this may be amongst the factors, which localise such damage. Tissue levels of PB-DOPA are increased in a number of age-related pathologies such as atherosclerosis and cataract formation. We discuss the detoxification, and the subsequent proteolysis and excretion of components of PB-DOPA. We contrast the fact that in marine organisms, and particularly in extracellular proteins, PB-DOPA and other DOPA-polymers can play important functional roles in adhesion and the provision of tensile properties.
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PMID:Metabolism of protein-bound DOPA in mammals. 1108 74

Two methods for the analysis of antioxidants, based on polyacrylamide gel electrophoresis (PAGE) and gel permeation high performance liquid chromatography (HPLC) were developed. Both of them exploit the variations of the signal (band or peak) given by human serum albumin (0.2% w/v in 100 mM sodium phosphate pH 7) upon oxidation with hypochlorite (1% of a solution containing 4% active Cl), quantitatively determined by densitometric analysis or peak integration. Based on such changes, two formulas were defined which allowed the determination of the antioxidant activity of ascorbic acid (EC(50,PAGE)=4.8x10(-4) M, EC(50,HPLC)=3.6x10(-4) M), glutathione (EC(50,PAGE)=1.5x10(-4) M, EC(50,HPLC)=2.0x10(-4) M) and melatonin (EC(50,PAGE)=5.2x10(-4) M, EC(50,HPLC)=3.2x10(-4) M), chosen as reference compounds. A good correlation was found between the activities of these substances in the two assays, which are also in good agreement with literature data, indicating that the two methods are essentially equivalent. These assays could be useful for the screening of new antioxidant drugs for pathological conditions such as cataract, rheumatic diseases, atherosclerosis and Alzheimer's disease.
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PMID:In vitro evaluation of antioxidant activity by electrophoresis and high performance liquid chromatography. 1111 64

Oxidative damage to proteins in the human lens is believed to be important in the etiology of age-related cataract. Because free radical-mediated oxidative damage to lipoproteins may accelerate atherosclerosis, the authors hypothesized that the development of cataract might be a marker for such damage and therefore might be associated with future risk of coronary heart disease (CHD). The authors followed 60,657 women aged 45--63 years and without known coronary disease, stroke, or cancer in 1984. During 10 years of follow-up (674,283 person-years), the authors documented 887 incident cases of CHD and 2,322 deaths. After adjustment for age, smoking, and other coronary risk factors, cataract extraction was significantly associated with higher risk of CHD (relative risk (RR) = 1.88, 95% confidence interval (CI): 1.41, 2.50) for total CHD, 2.44 (95% CI: 1.54, 3.89) for fatal CHD, and 1.63 (95% CI: 1.14, 2.34) for nonfatal myocardial infarction). The positive association between cataract extraction and total CHD was stronger among women with a history of diabetes (RR = 2.80, 95% CI: 1.77, 4.42) than among those without reported diabetes (RR = 1.51, 95 percent CI: 1.04, 2.18). In multivariate analyses, cataract extraction was associated with significantly increased overall mortality (RR = 1.37, 95 percent CI: 1.13, 1.66), which was entirely explained by the increased mortality from cardiovascular disease (RR = 1.84, 95% CI: 1.29, 2.64). These findings are compatible with current hypotheses relating oxidative damage and tissue aging to the development of cataract and CHD.
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PMID:Prospective study of cataract extraction and risk of coronary heart disease in women. 1132 18

Hyperglycemia leads to vascular disease specific to diabetes mellitus. This pathology, which results from abnormal proliferation of smooth muscle cells in arterial walls, may lead to cataract, renal failure, and atherosclerosis. The hexosamine biosynthetic pathway is exquisitely responsive to glucose concentration and plays an important role in glucose-induced insulin resistance. UDP-GlcNAc: polypeptide O-N-acetylglucosaminyltransferase (O-GlcNAc transferase; OGTase) catalyzes the O-linked attachment of single GlcNAc moieties to serine and threonine residues on many cytosolic or nuclear proteins. Polyclonal antibody against OGTase was used to examine the expression of OGTase in rat aorta and aortic smooth muscle (RASM) cells. OGTase enzymatic activity and expression at the mRNA and protein levels were determined in RASM cells cultured at normal (5 mM) and at high (20 mM) glucose concentrations. OGTase mRNA and protein are expressed in both endothelial cells and smooth muscle cells in the aorta of normal rats. In both cell types, the nucleus is intensely stained, while the cytoplasm stains diffusely. Immunoelectron microscopy shows that OGTase is localized to euchromatin and around the myofilaments of smooth muscle cells. In RASM cells grown in 5 mM glucose, OGTase is also located mainly in the nucleus. Hyperglycemic RASM cells also display a relative increase in OGTase's p78 subunit and an overall increase protein and activity for OGTase. Biochemical analyses show that hyperglycemia qualitatively and quantitatively alters the glycosylation or expression of many O-GlcNAc-modified proteins in the nucleus. These results suggest that the abnormal O-GlcNAc modification of intracellular proteins may be involved in glucose toxicity to vascular tissues.
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PMID:Hyperglycemia and the O-GlcNAc transferase in rat aortic smooth muscle cells: elevated expression and altered patterns of O-GlcNAcylation. 1133 5

Aspartic acid racemization (AAR) represents one of the major types of non-enzymatic covalent modification that leads to an age-dependent accumulation of abnormal protein in numerous human tissues. In vivo racemization is an autonomic process during the "natural" ageing of proteins, and correlates with the age of long-lived proteins. Consequently AAR can be used as molecular indicator of protein ageing as well as for the identification of permanent proteins that age with the human organism. Although long-living, structural proteins are mainly affected, AAR may be significant on a time scale also relevant to enzymes and signaling proteins. It may result in a loss of protein function due to proteolysis or due to changes in the molecular structure. In vivo racemization may also increase in pathological conditions. AAR has already been discussed as a relevant pathophysiological factor in the pathogenesis of diseases of old age such as atherosclerosis, lung emphysema, presbyopia, cataract, degenerative diseases of cartilage and cerebral age-related dysfunctions. Although the details of the biological consequences of AAR have to be further elucidated, it is evident that AAR plays a role in the molecular biology of ageing.
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PMID:Racemization of aspartic acid in human proteins. 1203 48

The RecQ family of DNA helicases have potential roles in DNA repair, replication and/or recombination pathways. In humans, a defect in the RecQ family helicases encoded by the BLM, WRN and RECQ4 genes gives rise to Bloom's (BS), Werner's (WS) and Rothmund-Thomson (RTS) syndromes, respectively. These disorders are associated with cancer predisposition and/or premature aging. In Bloom's syndrome, affected individuals are predisposed to many types of cancer at an early age. Werner's syndrome is a premature aging disorder with a complex phenotype, which includes many age-related disorders that develop from puberty, including greying and thinning of the hair, bilateral cataract formation, type II diabetes mellitus, osteoporosis and atherosclerosis. The phenotype of Rothmund-Thomson syndrome patients also consists of some features associated with premature aging, as well as predispositon to certain cancers. Here, we discuss the molecular basis of these RecQ helicase-deficient disorders.
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PMID:Premature aging in RecQ helicase-deficient human syndromes. 1220 42


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