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)

Studies have been made of the effects of X-ray on various lens reducing systems, including the levels of NADPH and glutathione (GSH), the activity of the hexose monophosphate shunt (HMS) and of certain enzymes, including GSH reductase, GSH peroxidase, and glucose-6-phosphate dehydrogenase (G-6-PG). It was found that during several weeks following X-irradiation but prior to cataract formation, there was very little change in the number of reduced -SH groups per unit weight of lens protein but that, with the appearance of cataract, there was a sudden loss of protein -SH groups. In contrast, the concentration of GSH in the X-rayed lens decreased throughout the experimental period. Similarly, the concentration of NADPH in the X-rayed lens was found to decrease significantly relative to controls 1 week prior to cataract formation, and the ratio of NADPH to NADP+ in the lens shifted at this time period from a value greater than 1.0 in the control lens to less than 1.0 in the X-rayed lens. A corresponding decrease occurred in the activity of the HMS in X-rayed lenses as measured by culture in the presence of 1-14C-labeled glucose, G-6-PD was partially inactivated in the X-rayed lens. Of the eight enzymes studied, G-6-PD appeared to be the most sensitive to X-irradiation. The data indicate that X-irradiation results in a steady decrease in the effectiveness of lens reducing systems and that when these systems reach a critically low point, sudden oxidation of protein -SH groups and formation of high-molecular-weight protein aggregates may be initiated.
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PMID:The effects of X-irradiation on lens reducing systems. 3 84

Cultured fibroblasts derived from a patient homozygous for galactokinase deficiency, his parents, and controls had similar rates of growth in culture media where the only hexose was glucose. However, in media where the only hexose was galactose there was almost no growth of homozygous mutant cells or of maternal heterozygous cells and slight growth of paternal heterozygous cells. Growth of control cells was initially slow, but after a lag period (which coincided with increasing galactokinase activity) growth reached approximately the same levels as in glucose medium. In all cell lines there was a direct relation between the degree of enhancement of galactokinase activity and the ability of cells to adapt to growth in media where the only hexose was galactose. Erythrocyte galactokinase activities in a series of 24 children children with congenital cataracts aged 2-16 years were similar to those in 26 controls. One child in each of the cataract and control groups had 40-50% of mean control activity and was considered to be a potential heterozygote. Galactokinase deficiency (homozygous and heterozygous) is considered to be an uncommon cause of childhood cataracts. Nevertheless, it is an important cause since early dietary treatment can prevent or reverse lens opacities. The heterozygous state may be expressed phenotypically in the patient by the appearance of cataracts and in cultured cells by their defective growth in media where galactose is the only hexose.
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PMID:Phenotypic expression of galactokinase deficiency in heterozygous and homozygous subjects: in vivo and in vitro studies. 18 97

The role of reduced glutathione (GSH) in lens membrane function was studied by depleting GSH with 1-chloro-2,4-dinitrobenzene (CDNB), a reaction catalyzed by GSH-S-transferase. Depletion of GSH in the lens epithelium by 70-90% led to a decrease in uptake and increase in efflux of 86Rb. ATP levels and Na+/K+-ATPase activity were normal while there was a slight decrease in lactate production. The results provide the first direct evidence that depletion of endogenous GSH per se does not lead to inactivation of Na+/K+-ATPase. However, lenses deficient in GSH when challenged with a normally tolerated level of H2O2 showed significant inactivation of membrane ATPase without a further increase in membrane permeability. Pretreatment with CDNB resulted in a 3-fold stimulation of the hexose monophosphate shunt activity which is attributed to the unexpected finding of a significant increase in the level of oxidized glutathione in the lens. It is concluded that deficiency of GSH causes a marked increase in membrane permeability and such lenses are susceptible to oxidative damage resulting in inactivation of the Na+/K+ pump, thus leading to ionic changes and cataract development.
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PMID:Effect of glutathione depletion on cation transport and metabolism in the rabbit lens. 318 92

Previous studies have indicated that in vivo exposure to hyperbaric O2 may be associated with the development of nuclear cataract. In the present work, in vitro effects of hyperbaric O2 on rabbit lenses were investigated following culture of the lenses in an atmosphere of 99% O2 at pressures ranging between 1 and 100 atm. Treatment with O2 resulted in a significant decrease in the level of reduced glutathione (GSH) in the lenses even at the lower pressures studied (less than 8 atm). At 100 atm O2 the loss of GSH was 85% after a 3 hr exposure. At 8 atm O2 a significant drop in GSH concentration was shown to occur in the lens nucleus prior to loss of the tripeptide in the superficial cortex. O2-treated lenses became hazy in appearance, especially at the higher pressures, but did not become densely opaque. Pressures of N2 up to 100 atm had no effect on either lens transparency or on the concentration of GSH. Although oxidized glutathione (GSSG) was detected in the whole lens at pressures of O2 as low as 4 atm, no change in GSH level or evidence for GSSG accumulation was observed in the capsule-epithelium of the lens at pressures as high as 50 atm O2. Ninety percent of the GSSG present in lenses after exposure to 100 atm O2 could be reconverted to GSH by subsequent culture of the lenses under normal conditions. Exposure of lenses to 50 atm O2 produced a three-fold stimulation of hexose monophosphate shunt activity, equal to that which has been reported for treatment of lenses with 0.06 mM H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exposure of rabbit lens to hyperbaric oxygen in vitro: regional effects on GSH level. 341 15

Addition of pyrroline-5-carboxylate (P5C) or its precursors to rat lenses cultured for 24 hr in TC-199 medium containing 14C-glucose results in an apparent concentration-dependent increase in hexose monophosphate-pentose (HMP) pathway activity. Addition of proline, the reduction product of P5C, did not result in an increase, suggesting that stimulation of the HMP pathway is related to the reduction of P5C to proline by the enzyme P5C reductase. No apparent feedback inhibition on P5C reductase was observed. Stimulation of HMP pathway activity by P5C was also observed in the lenses of Philly and Nakano mouse, two models of congenital osmotic cataracts. Compared with its genetic control, the Swiss--Webster mouse, generally no difference in the lenticular levels of HMP pathway activity was observed in the Philly mouse--even after the onset of cataract. Stimulation of the HMP pathway in the Philly lens by P5C, however, was consistently lower than its control. In the lenses from the Nakano mouse and its genetic control, the Balb/c mouse, no difference in the percentage stimulation of the HMP pathway resulting from the addition of P5C was observed, but HMP pathway activity in the Nakano lens was consistently lower than that of the control.
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PMID:Stimulation of the hexose monophosphate pathway by pyrroline-5-carboxylate reductase in the lens. 384 59

Assay of the activities of hexokinase, phosphofructokinase, and pyruvate kinase showed that the first two declined in aging human lens cortex and all three enzymes retained constant activities in the epithelium throughout life. Moreover, both clear and cataractous aging lenses contained the same enzyme activities. ATP contents in cataracts, however, were lower than in clear lenses; in fact, after incubation at 37.5 degrees C in isotonic (290 to 300 mOsm), glucose-containing media, ATP was rapidly lost from cataracts (but not from clear lenses), suggesting excessive ATP expenditure in cataracts for osmotic balance. Cataracts incubated in media containing either glucose-6-phosphate or fructose-1, 6-diphosphate produced significantly higher ATP than with glucose in the media, indicating that glucose metabolism in human senile cataracts could be supplemented with hexose phosphates. Fructose-1, 6-diphosphate appeared to be more efficient than glucose-6-phosphate in preventing lens swelling during incubation.
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PMID:Supplementing glucose metabolism in human senile cataracts. 645 78

The mammalian lens contains an unusually high concentration of glutathione (GSH), the highest level being in the epithelium. GSH is present largely in the reduced state. The high concentration of GSH in a normal lens and the decreased concentration in most types of cataracts have led to many hypotheses on its role in cataract formation. These hypotheses are considered in the light of current evidence. GSH is synthesized and degraded in the lens. Both processes require ATP, derived largely from glycolysis. Carbohydrate metabolism is also involved in the maintenance of GSH in the reduced state. There is a direct link between the rate of formation of oxidized glutathione (GSSG) and the stimulation of the hexose monophosphate shunt through the generation of NADPH. One possible function of GSH in the lens is to maintain the thiol (SH) groups of proteins in the reduced state, thus preventing formation of high molecular weight (HMW) protein aggregates. The formation of HMW proteins in X-ray-induced cataracts through disulphide bond formation and the involvement of SH oxidation in HMW proteins isolated from human cataractous lenses suggest a role for GSH in protecting protein SH groups. GSH in the lens may also protect critical SH groups involved in regulating cation transport and permeability. Studies with mammalian lenses indicate that lowering the lens GSH concentration leads to increased permeability to cations and inactivation of Na+,K+-ATPase. A consequence of the changes in ion distribution is the inhibition of protein synthesis, which may explain the cessation of growth in cataractous lenses. GSH may also protect against oxidative damage to the lens. GSH metabolism is intimately involved in detoxification of H2O2, normally present in the aqueous humour. Lenses with impaired shunt activity or inhibited glutathione reductase are more susceptible to oxidative damage by peroxide. This may contribute to the formation of cataract.
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PMID:Metabolism and function of glutathione in the lens. 656 81

Previously by selection and inbreeding of Wistar rats susceptible or resistant to the cataractogenic effect of galactose the S and R rat strains differing in the intensity of hexose transport into the animal cells were developed. High level of OH-radical generation and enhanced lipid peroxidation are revealed in the liver and myocardium of the S rats in contrast to the R rats. Data are obtained supporting the view that enhanced generation of OH-radicals within the S rat tissues is due to oxidation and autooxidation of the abundant amounts of monosacharides intensely accumulating in the rat cells. In spite of continuous inbreeding for more than 40 generations and a high rate of homozygosity, numerous DNA rearrangements are revealed in the S rat genomes. Fragility of the S rat cell membranes is detected. Cataracts and other lens lesions, emphysema, tumors, cardiomyopathy-like changes in the myocardium, scoliosis, brain disfunctions are characteristic of the S rats, as well as low fertility and short life-span indicative of premature aging.
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PMID:Inherited enhancement of hydroxyl radical generation and lipid peroxidation in the S strain rats results in DNA rearrangements, degenerative diseases, and premature aging. 813 16

Glucose-6-phosphate dehydrogenase (G6PDH) is an important lens enzyme diverting about 14% of the tissue glucose to the hexose monophosphate shunt pathway. The main function of such a pronounced activity of the enzyme is to support reductive biosyntheses, as well as to maintain a reducing environment in the tissue so as to prevent oxy-radical induced damage and consequent cataract formation. Sugars are one of the well-known cataractogenic agents. Several reports suggest that the cataractogenic effect of the sugars in diabetes as well as in normal aging is initiated by the glycation of the proteins including the enzymes and subsequent formation of more complex and biologically inactive or harmful structures. In a diabetic lens the concentration of fructose exceeds significantly the concentration of glucose, suggesting that the contribution of fructosylation may be greater than that of glucosylation. These studies were undertaken to examine further the possibility that in addition to glycation, generation of oxygen free radicals by fructose and consequent oxidative modifications in certain enzymes may be an important participant in the cataractogenic process. This hypothesis was tested by using G6PDH. The enzyme was incubated with various levels of fructose (0-20mM) and its activity determined as a function of time. This led to a significant loss of its activity, which was prevented by superoxide dismutase, catalase, mannitol and myoinositol. Most interestingly, pyruvate at levels between 0.2 and 1.0 mM also offered substantial protection. Hence, the results, while elucidating further the mechanism of enzyme deactivation by sugars such as fructose, also demonstrate the possibility of therapeutic prevention of cataracts by pyruvate and other such keto acids, in diabetes and other disabilities involving oxygen free radicals in the pathogenetic process.
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PMID:Fructose induced deactivation of glucose-6-phosphate dehydrogenase activity and its prevention by pyruvate: implications in cataract prevention. 986 46

We studied the energy metabolism of cataracts induced by ultraviolet (UV) irradiation by observing metabolic changes in lenses using 31P-, 1H-, and 13C-nuclear magnetic resonance (NMR) spectroscopy. % of hexose monophosphate shunt flux activity increased over time. The lactate/glucose ratio in the UV irradiation group decreased to about half of that of the corresponding control group (11.6 +/- 2.0% vs. 20.7 +/- 1.7%, respectively, p < 0.05) after 10 h of irradiation and to about 30% of that of the control group (25 +/- 2% vs. 92 +/- 6%, respectively) after 24 h. The adenosine triphosphate (ATP) level significantly decreased after 3 h of irradiation (86 +/- 29%, p < 0.05) and continuously decreased to 68 +/- 33% (p < 0.01) after 10 h of irradiation and 26 +/- 2% (p < 0.01) after 24 h of irradiation. Conversely, a significant increase in inorganic phosphate (Pi) was observed after 1 h of irradiation (111 +/- 26%, p < 0.05), and the Pi level gradually increased to 140 +/- 28% after 10 h of irradiation (p < 0.01) and 207 +/- 26% after 24 h (p < 0.01). A significant decrease in alpha-glycerophosphate was noted after 24 h (38 +/- 13%, p < 0.01). The ribose-5-phosphate (R-5-P) level gradually increased after irradiation to 128 +/- 13% (p < 0.05) after 10 h and 141 +/- 21% after 24 h (p < 0.01). The results suggest that of these metabolic changes a marked decline in glycolytic production of ATP, which inhibits membrane metabolism, may be an important cataract-inducing factor following UV irradiation.
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PMID:Metabolic changes during cataract formation by ultraviolet radiation in the incubated rabbit lens. 1999 18


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