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)

Tocopherols and tocotrienols (vitamin E) and ascorbic acid (vitamin C) as well as the carotenoids react with free radicals, notably peroxyl radicals, and with singlet molecular oxygen (1O2), this being the basis of their function as antioxidants. RRR-alpha-tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins (LDL). L-Ascorbate is present in aqueous compartments (e.g. cytosol, plasma, and other body fluids) and can reduce the tocopheroxyl radical; it also has a number of metabolically important cofactor functions in enzyme reactions, notably hydroxylations. Upon oxidation, these micronutrients need to be regenerated in the biological setting, hence the need for further coupling to nonradical reducing systems such as glutathione/glutathione disulfide, dihydrolipoate/lipoate, or NADPH/NADP+ and NADH/NAD+. Carotenoids, notably beta-carotene and lycopene as well as oxycarotenoids (e.g. zeaxanthin and lutein), exert antioxidant functions in lipid phases by free-radical or 1O2 quenching. There are pronounced differences in tissue carotenoid patterns, extending also to the distribution between the all-trans and various cis isomers of the respective carotenoids. Antioxidant functions are associated with lowering DNA damage, malignant transformation, and other parameters of cell damage in vitro as well as epidemiologically with lowered incidence of certain types of cancer and degenerative diseases, such as ischemic heart disease and cataract. They are of importance in the process of aging. Reactive oxygen species occur in tissues and cells and can damage DNA, proteins, carbohydrates, and lipids. These potentially deleterious reactions are controlled in part by antioxidants that eliminate prooxidants and scavenge free radicals. Their ability as antioxidants to quench radicals and 1O2 may explain some anticancer properties of the carotenoids independent of their provitamin A activity, but other functions may play a role as well. Tocopherols are the most abundant and efficient scavengers of peroxyl radicals in biological membranes. The water-soluble antioxidant vitamin C can reduce tocopheroxyl radicals directly or indirectly and thus support the antioxidant activity of vitamin E; such functions can be performed also by other appropriate reducing compounds such as glutathione (GSH) or dihydrolipoate. The biological efficacy of the antioxidants is also determined by their biokinetics.
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PMID:Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. 144 60

The evidence reviewed here supports the hypothesis that metal catalyzed oxidation reactions occur in the lens and may make a significant contribution to the changes seen in the lens with age and in cataract formation. The major support for this hypothesis is as follows. (1) All of the components of the non-enzymic metal catalyzed oxidation systems are present in the lens normally. Ascorbate, glutathione and oxygen are present in much lower concentrations. Although, even at low concentrations, the reactions could occur over many years with significant consequences. Components of some of the enzymic systems are also present, although primarily in the epithelial layer and outer cortical region. Copper and iron levels may be increased in some cataracts. (2) Protein carbonyl derivatives are increased in both aging and cataractous lenses. Amino acid-derived protein carbonyl derivatives have only been demonstrated in oxidative reactions derived from oxygen radical generation, particularly those catalyzed by metal-catalyzed oxidation systems. (3) Treatment of isolated bovine crystallins with metal catalyzed oxidation systems generates modifications similar to those found in vivo. The proposed mechanism of site-specific metal catalyzed oxidation appears to be a feasible mechanism of oxidation in the lens, and verification of the mechanism requires further study. Although the focus of this manuscript has been on the oxidative modification induced in proteins,m oxidative damage to DNA or membrane resulting from similar mechanisms may also play an important role in alteration of lens function during aging and cataractogenesis.
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PMID:Role of site-specific, metal-catalyzed oxidation in lens aging and cataract: a hypothesis. 219 8

Exposure of mice to hyperbaric oxygen leads to an inhibition of the mitotic activity in the germinative epithelium of the lens. This is followed by an eventual development of cataracts. Cataracts have also been observed in human beings treated with hyperbaric oxygen for different afflictions. The lens damage and cataract formation appears to be due to in situ generation of active radicals and other active species of oxygen. These oxygen derivatives may also contribute to the multifactorial process of senile cataract formation in human beings. This hypothesis is based on in vitro experiments with rat lenses cultured in medium generating oxygen radicals, the generation of the radicals being accomplished either photochemically or enzymatically. The ability of the lens to transport rubidium and amino acids from such a medium is adversely affected. This is a recognized index of the damage to the tissue physiology. Scavengers of active oxygen species have been found to protect against this damage. Ascorbate, present in concentrations similar to that in the primate aqueous and lens, is also protective. The studies, therefore, point to an antioxidant and perhaps an anti-cataract effect of ascorbate. Pyruvate is another agent useful in this regard.
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PMID:Ascorbic acid and the eye lens. 318 90

Large accumulations of postsynthetically oxidized proteins are observed in the aged and cataractous eye lens. Ascorbate has previously been used to delay photooxidative damage in vitro. The goals of this study were to confirm that dietary ascorbate can be used to enhance lens ascorbate levels and to determine if lenses with enhanced ascorbate can better withstand photooxidative stress in the form of ultraviolet (UV) light exposure. Guinea pigs were placed on high dietary ascorbate (HDA), 50 mg/day, and low dietary ascorbate (LDA), 2 mg/day, for 21 weeks. Lenses from HDA animals were found to contain 3.3 times more ascorbate than LDA animals. Prior to irradiation, SDS-PAGE protein profiles and exopeptidase activity in HDA and LDA lens soluble proteins were indistinguishable. However upon exposure to UV light, more protein damage (e.g., high-molecular-weight aggregates and enhanced loss of exopeptidase activity) was seen in lens preparations from LDA as compared to HDA animals. These results suggest that ascorbate protects lens components against cataract-like and age-related postsynthetic changes in vivo. As in previous tests on lens preparations, attenuated exopeptidase activity was observed before protein aggregation.
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PMID:Delay of UV-induced eye lens protein damage in guinea pigs by dietary ascorbate. 329 91

This paper focuses on damage to soluble lens proteins during ultraviolet (UV) light exposure and its prevention by ascorbate (Vitamin C). Using 2.3 X 10(-3) W/cm2 UV A and 0.4 X 10(-4) W/cm2 UV B, aminopeptidase inactivation in lens supernatants is significant after 60 min. Protein aggregation and decreases in tryptophan levels, phenomena associated with UV-induced and cataract-related damage, are observed only after longer (6 h) UV exposure. Thus, it would appear that measurements of aminopeptidase activity can be used to anticipate damage to lens structural proteins. Ascorbate (15 mM) added to soluble lens proteins prior to photoirradiation can prevent some of these changes. The data presented suggest plausible relationships between impaired proteolysis and cataract formation.
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PMID:Measures of leucine aminopeptidase can be used to anticipate UV-induced age-related damage to lens proteins: ascorbate can delay this damage. 343 Nov 68

Lens retrodots are round, oblong, or oval features in the perinuclear zone of the adult lens after the fifth decade of life and associated with cataract. Retrodots were found in 47 out of 121 eyes with cataract (39%) in the present series. They show birefringence in vivo and in vitro, and chemical studies suggest that they contain calcium oxalate. It is proposed that ascorbic acid, which is abundant in the normal human lens, is the most likely source for this oxalate. Ascorbic acid is thought to have a protective role against oxidative stress in the lens and other parts of the eye, and its level is known to be reduced in senile cataract. The presence of the retrodots may identify lenses which have been exposed to oxidative stress and are less capable of resisting oxidative damage.
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PMID:Perinuclear lens retrodots: a role for ascorbate in cataractogenesis. 382 68

Ascorbate (vitamin C) degradation products can undergo non-enzymatic glycation (Maillard reaction) with proteins to form highly crosslinked structures with brown pigmentation and characteristic fluorescence. Proteins in the body, especially the long-lived proteins develop similar changes during aging and diabetes. Several studies have shown excessive degradation of ascorbate in plasma in diabetes, and in ocular lens during aging and cataract formation. Recent studies have suggested that ascorbate degradation products-mediated glycation plays a role in lens pigmentation and cataract formation. However, the precise chemical nature of ascorbate-specific advanced glycation end-products are not known. Here, we report the purification and characterization of a glycation end-product derived from one of the major degradation products of ascorbate, L-threose. This compound was characterized to be 2-acetamido-6-(3-(1,2-dihydroxyethyl)-2-formyl-4-hydroxymethyl-1- pyrrolyl)hexanoic acid (formyl threosyl pyrrole or FTP) formed by the condensation of epsilon-amino group of lysine with two molecules of threose. Formation of FTP occurred rapidly in the incubation of threose and lysine and reached plateau level within a day. We have developed a sensitive assay for its quantification in proteins based on enzyme digestion followed by HPLC. Ribonuclease A and human lens crystallins incubated with L-threose showed time- and sugar concentration-dependent increases in FTP, reaching 8.2 and 2.48 nmol per mg protein, respectively after one week of incubation. Human plasma proteins showed a peak with identical retention time as that of purified FTP under two different HPLC conditions. FTP may be used as a sensitive marker to assess ascorbate-mediated protein glycation and modifications in aging and diabetes.
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PMID:Protein modification by the degradation products of ascorbate: formation of a novel pyrrole from the Maillard reaction of L-threose with proteins. 749 3

The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.
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PMID:Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer. 754 Jul 4

Dietary restriction can effectively extend lifespan and retard many age-related debilities. One hypothesis to explain the beneficial effects of dietary restriction is that it prolongs maintenance of cellular homeostasis by limiting endogenous oxidative stress and preserves oxidative defense mechanisms during aging. Ascorbate, a primary antioxidant, may play a major role in preventing oxidative damage. Ascorbate levels were determined in dietary restricted (R) and control (C) Emory mice, a strain which develops age-related cataract due in part to oxidative damage to lens proteins. Mice which consumed a diet restricted by 40% in calories had lower ascorbate concentrations in plasma, liver and kidney. Nevertheless, R animals showed significantly delayed progression of cataract which extended over the entire second half of life. The R diet did not result in different ascorbate levels in this lens. Aging was associated with a decrease in ascorbate in all the examined tissues except lens of both the R and C groups. It is not clear from these data that ascorbate is a prominent factor in the delay of cataract formation or other debilities in R Emory mice. However, it also appears unlikely that lens ascorbate is cataractogenic.
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PMID:Dietary restriction delays cataract and reduces ascorbate levels in Emory mice. 755 70

Estimation of cadmium and vitamin C was performed in the blood and lens of smokers in three age groups up to a maximum age of 58, habituated to smoking a minimum of 10 beedies a day for many years, as well as those of non-smokers in the same age groups. Only nuclear cataracts with or without posterior or anterior subcapsular cataract were chosen. It was found that there was a significant accumulation of cadmium in both the blood and the lens of the smokers. Such an accumulation of cadmium might have a role in cataractogenesis in chronic smokers. In a similar experiment, with smokers and non-smokers of two age groups up to a maximum age of 40, both without cataract, increased levels of cadmium were found in the blood of smokers only, though the extent of accumulation was not as high as in chronic smokers of higher age groups. Vitamin C content of lens was on the lower side of normal in both chronic smokers of beedies in the two age groups and non-smokers with nuclear cataract with or without posterior and anterior subcapsular cataract, and there was no significant change brought about by smoking. Vitamin C levels in blood were towards the lower side of the normal in smokers and non-smokers with and without cataract.
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PMID:Smoking of beedies and cataract: cadmium and vitamin C in the lens and blood. 770 92


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