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)

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

In this study we have investigated the oxidative metabolism of red blood cells (RBC), plasma, serum, aqueous humor, and lens of healthy subjects and of age-matched cataractous patients with and without diabetes. Reduced and oxidized glutathione (GSH GSSG) levels in RBC were similar among the three groups. Plasma levels of GSSG were higher in diabetics than in cataractous and control subjects. No differences in plasma content of GSH were noted among the three groups. The activity of the enzyme glucose-6-phosphate dehydrogenase was significantly diminished in diabetic patients. Controls and cataractous patients showed similar levels of malondialdehyde (MDA). Although not significant the MDA content in RBC from diabetics was elevated. No differences in plasma levels of vitamin E were noted among the three groups. The biological liquid oxidant activity of serum in diabetic patients was significantly higher than in controls and cataractous patients. GSH levels in aqueous humor were similar in diabetic and nondiabetic cataractous patients. The content of GSSG in aqueous humor was highest in diabetic patients. Control clear lenses showed low levels of MDA. The MDA levels in cataractous lenses from nondiabetic patients were significantly higher than those of controls. In diabetic patients the content of MDA in the lens was approximately twice as high as the cataractous values. Our results seem to demonstrate that oxidative damage could play a role in the pathogenesis of cataract in diabetes.
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PMID:Systemic human diseases as oxidative risk factors in cataractogenesis. I. Diabetes. 318 3

Acetaminophen has been shown to be cataractogenic in mice and rabbits. C57BL/6 and DBA/2 mice respectively are genetically susceptible and resistant to the induction of cytochrome P-448 by 3-methylcholanthrene (3-MC). This isoenzyme is thought to bioactivate acetaminophen to a toxic reactive intermediate. These two murine strains also are correspondingly susceptible and resistant to acetaminophen cataractogenesis. To evaluate the potential role of enzymatic bioactivation as a determinant of acetaminophen cataractogenesis, C57BL/6 and DBA/2 mice were treated with acetaminophen, 300 or 400 mg/kg intraperitoneally (ip), with or without pretreatment 48 hr earlier using 3-MC, 200 mg/kg ip. Lenticular cataracts were evaluated using the unaided eye and a slit lamp, and hepatotoxicity was evaluated by determination of peak plasma concentration of alanine aminotransferase (ALT). Plasma concentrations of acetaminophen and metabolites, particularly the glutathione (GSH)-derived conjugates (cysteine and mercapturic acid) reflecting enzymatic bioactivation, were measured by high-performance liquid chromatography. Cataracts developed only in C57BL/6 mice pretreated with 3-MC, occurring in 1 of 5 and 5 of 5 animals treated respectively with 300 and 400 mg/kg of acetaminophen. Comparing these two groups of induced C57BL/6 mice, production of the cysteine conjugate of acetaminophen was 2.5-fold higher with the 400 mg/kg dose of acetaminophen (p less than 0.05). Compared to their respective dose-matched, noninduced controls, cysteine conjugate production in the 300 and 400 mg/kg dose groups of induced C57BL/6 mice respectively was 3-fold and 4-fold higher (p less than 0.05). No DBA/2 mice developed cataracts. No mercapturic acid conjugate was detectable in the plasma of DBA/2 mice, and production of the cysteine conjugate was not altered in this strain by increasing the dose of acetaminophen or by pretreatment with 3-MC. The mean peak plasma concentration of the cysteine conjugate, reflecting acetaminophen bioactivation, was 5-fold higher in animals developing cataracts compared with those without cataracts (p less than 0.001). Plasma concentrations of unmetabolized acetaminophen were similar in all groups and unrelated to the development of cataracts. All mice of both strains pretreated with 3-MC showed evidence of hepatotoxicity, indicating a dissociation between hepatotoxic and cataractogenic susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolic evidence for the involvement of enzymatic bioactivation in the cataractogenicity of acetaminophen in genetically susceptible (C57BL/6) and resistant (DBA/2) murine strains. 340 97

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

The effect of (1-benzoyl-1H-indazol-3-yl)oxylacetate L-Lysine (bendazac-lysine) on some enzymatic activities involved in the metabolism of reduced glutathione (GSH) was studied in the rabbit lens during developing cataract induced by a single dose of X-rays (2000 rads). The specific activities of glutathione reductase (G.R.), glutathione peroxidase (GSH.Px) and glutathione S-transferase (GSHS-tr.) do not change following irradiation and treatment with bendazac-lysine. The activity of the same enzymes expressed as a function of water soluble proteins (WSP) per lens significantly decreases (P less than 0.01) as compared to controls in the irradiated lens not treated with bendazac-lysine (ILNTB) at the 8th week, whereas no significant decrease as compared to controls is observed in the irradiated lens treated with bendazac-lysine (ILTB). In the ILNTB the specific activity of glucose-6-phosphate dehydrogenase (G6PDH) is reduced by 10% after 0.3 weeks and by 29% after 12 weeks. In the ILTB the specific activity of G6PDH is reduced by 8% after 0.3 weeks and by 14.5% after 12 weeks. The specific activity of superoxide dismutase (SOD) in the ILNTB is reduced by 19% after 0.3 weeks and reached 31% after 12 weeks. In the ILTB the specific activity of SOD is reduced by 11% after 0.3 weeks and 19.8% after 12 weeks. The mechanism of protective effect of bendazac-lysine on cataract is discussed.
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PMID:Effects of bendazac L-lysine salt on some metabolic enzymes of glutathione in the rabbit lens after X-irradiation. 361 May 98

The disposition and disposal of the -SH groups of the lens during aging and cataractogenesis have been investigated by laser Raman spectroscopy as a noninvasive microprobe in the intact living lens. In this procedure -SH and -S-S- give unique discrete Raman signals (at 2580 and 508 cm-1) that may be used to calculate relative concentrations in a very small volume of the lens. We present evidence showing an unexpected and remarkable difference with respect to these groups between the mouse lens and the lenses of guinea pig and man. The mouse lens nucleus exhibits a precipitous fall in the -SH concentration on aging from 1 to 6 months; concomitantly, there is a rise in -S-S- of comparable magnitude, indicating a direct conversion. The guinea pig lens, however, is quite different with respect to the age-dependent change in nuclear -S-S-: there is none between 6 months and 5 years. In the human lens -S-S- behaves exactly as in the guinea pig lens: the level is low and does not change with age between 9 and 65 years. With respect to nuclear -SH, these two latter species of lenses show some decrease with age but nothing like the approach to zero found in the aging mouse lens nucleus. These differences involving lenticular -SH and -S-S- appear to be correlated with the hard nucleus in the mouse lens and the softer nuclei of lenses in guinea pigs and humans. The relatively high level of -S-S- in the old but clear mouse lens does not support the idea that protein aggregation involving formation of intermolecular -S-S- bonds is necessarily an important cause of nuclear cataract. The small but significant age-related depression of -SH in guinea pig lens nuclei without any accumulation of -S-S- may be explained as a result of glutathione (GSH) oxidation and subsequent extrusion of glutathione disulfide (GSSG) by the lens. We propose that the oxidation of glutathione proceeds by reaction with protein disulfide groups to yield protein sulfhydryl (PSH) and a mixed disulfide of glutathione and protein; the mixed disulfide is capable of being reduced by glutathione reductase and NADPH, yielding the original PSH and GSSG, which is extruded from the lens. It remains to be determined if this mechanism is more active in guinea pig and human lenses than in the mouse lens.
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PMID:Disulfide bond formation in the eye lens. 386 9

1. Cataracts were developed by incubating rabbit lenses for 22hr. at 37 degrees in a culture medium containing tyrosine and tyrosinase (EC 1.10.3.1). 2. A 45% diminution in the content of GSH and significant inhibition of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) activity were observed in the cataractous lenses compared with controls. 3. GSSG accumulated in both cataractous and control lenses. Significant amounts of GSSG were transported outward from the cataractous lenses and small amounts from control lenses. 4. Transport of GSSG from rabbit lens incubated in a diffusate of plasma from a naphthalene-fed rabbit was also observed. 5. GSSG was found in the aqueous humour obtained between 2 and 24hr. after feeding of naphthalene to rabbits; subsequently the GSSG in the aqueous humour decreased to almost undetectable amounts in 48hr.; in controls, GSSG was not detectable. 6. A possible mechanism of formation of experimental and senile cataract is briefly discussed.
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PMID:Cataract produced by tyrosinase and tyrosine systems in rabbitens in vitro. 497 83

A new method has been developed for the conjugation of rat lens glutathione by 1-chloro-2,4-dinitrobenzene (CDNB). This reaction is catalysed by glutathione S-transferase present in the lens. One milliliter of 1 mM CDNB per two rat lenses conjugates more than 95% of the lens GSH in 30 min at 37 degrees. Lenses incubated with 1 mM CDNB for 30 min, followed by incubation in the culture medium without CDNB remained apparently clear for up to 24 hrs. The CDNB treated lenses were more susceptible to protein precipitation (cataract formation) when challenged with oxidants such as hydrogen peroxide and superoxide anions.
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PMID:Role of glutathione in the prevention of cataractogenesis in rat lenses. 629 3

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

A dose of 20 mumol selenite/kg body weight is a potent and a very rapid inducer of cataracts in young rats. We investigated the rate at which physiological concentrations of selenite would catalyze the oxidation of glutathione in vitro and found that selenite was a strong sulfhydryl oxidant. To test if selenite had the same effect in vivo, the oxidation state of five kinds of lenticular sulfur were measured in suckling rats following a cataractous dose of selenite. The measurements included reduced glutathione (GSH), oxidized glutathione (GSSG), protein-bound glutathione ( PSSG ), reduced protein sulfhydryl ( PSH ), and oxidized protein sulfhydryl ( PSSP ). While selenite caused a 44% decrease in lens GSH by 6 days postinjection, there was no concurrent increase in either GSSG or PSSG . Likewise, there was no evidence for increased oxidation of PSH to PSSP . To determine if GSH loss were the cause of the selenite cataracts, we injected normal rats with the glutathione synthesis inhibitor buthionine sulfoximine (BSO). Lens GSH dropped more than 96% by 4 days post-BSO injection; however, no cataracts formed. Thus, selenite cataract does not appear to be caused by extensive sulfhydryl oxidation and cannot be attributed exclusively to GSH loss.
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PMID:State of sulfhydryl in selenite cataract. 672 15


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