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 aim of the present study was to investigate biochemical and morphological changes in rat lenses following long-term UV B irradiation. After an irradiation period of 156 days with follow-up documentation by means of Scheimpflug photography, section-related biochemical analyses of the lenses as well as histological investigations were performed. The video-based Scheimpflug photography (Zeiss SLC) again proved to be an excellent method for the documentation of the UV cataract induced in rats. The biochemical analyses provided indications to potential damaging mechanisms; the section-related technique used allows more precise analyses than the processing of whole lenses in a cataract type restricted to a certain layer, as is the case with UV B damage. The most prominent biochemical findings were a significant decrease in glyceraldehyde-3-phosphate dehydrogenase in the equatorial region in the group with the highest irradiation dosage and a decrease in lactate dehydrogenase in the nuclear region. The histological results reflect the local extent of the UV damage as well as its progression after a prolonged irradiation period.
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PMID:Biochemical and morphological changes in rat lenses after long-term UV B irradiation. 128 10

Oxidative stress is known to cause cataracts in lens culture systems and is believed to be an important factor contributing to human cataracts. In this communication, it is demonstrated that cataract development of cultured rat lenses produced as a result of photochemically induced oxidation in a 4% oxygen atmosphere similar to the native environment of the lens can be blocked by the transition metal complex AL-3823A. In this system, riboflavin is added to the medium as a photosensitizer. AL-3823A acts primarily as a glutathione peroxidase mimic, which catalytically metabolizes H2O2 and also has low superoxide dismutase-like activity. Measurements of H2O2, O2.-, and OH. indicate that appreciable levels of the first two of these oxidants and low levels of OH. are produced by this photochemical stressing system. The H2O2 concentrations are similar to those found in some patients with cataracts. The development of cataracts was followed over a 96-hr period. Transparency, hydration, glyceraldehyde-3-phosphate dehydrogenase activity, and protein and nonprotein thiol were monitored. All parameters show marked changes during the 96-hr period. However, in the presence of 200 microM AL-3823A, no difference between control and light-exposed lenses was observed with respect to these parameters. The results suggest that in vivo human cataract development caused by oxidative stress may be prevented by compounds of this type.
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PMID:Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic. 835 43

The aim of this study was to estimate the anticataract action of vitamin E using an in vitro methylprednisolone (MP)-induced cataract model. The same severity of early cortical cataract was induced in lenses isolated from male Wistar rats aged 6 weeks by incubation with MP (1.5 mg/ml) in TC-199 medium. The cataractous lenses showed slight increases in lipid peroxide (LPO) content and Na+/K+ ratio and slight decreases in reduced glutathione (GSH) content and glyceraldehyde-3-phosphate dehydrogenase (GAP-DH), a sensitive index of oxidative stress, and Na+,K(+)-ATPase activities. When the cataractous lenses were further incubated in TC-199 medium with and without vitamin E (250 micrograms/ml) for 48 h, the progression of cataract was prevented in the vitamin E-treated lenses, but not in the vitamin E-untreated lenses. The vitamin E-untreated lenses showed a decrease in vitamin E content and an increase in water content in addition to further increases in LPO content and Na+/K+ ratio and further decreases in GSH content and GAP-DH and Na+,K(+)-ATPase activities. In contrast, the changes of these components and enzymes except for GSH were attenuated in the vitamin E-treated lenses. From these results, it can be estimated that vitamin E prevents in vitro cataractogenesis in rat lenses treated with MP by protecting the lenses against oxidative damage and loss of membrane function.
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PMID:Anticataract action of vitamin E: its estimation using an in vitro steroid cataract model. 888 85

The high content of glutathione (GSH) in the lens is believed to protect the thiols in structural proteins and enzymes for proper biological functions. The lens has both biosynthetic and regenerating systems for GSH to maintain its large pool size (4-6 mM). However, we have observed that, in aging lenses or lenses under oxidative stress, the size of GSH pool is diminished; and some protein thiols are being S-thiolated by oxidized nonprotein thiols to form protein-thiol mixed disulfides, either as protein-S-S-glutathione (PSSG) or protein-S-S-cysteine (PSSC). We have shown in an H2O2-induced cataract model that PSSG formation precedes a cascade of events starting with protein disulfide crosslinks, protein solubility loss, and eventual lens opacification. Recently, we discovered that this early oxidative damage in protein thiols could be spontaneously reversed in H2O2 pretreated lenses if the oxidant was removed in time. This dethiolation process is likely mediated through a redox regulating enzyme, thioltransferase (TTase), which has been discovered recently in the lens. To understand if the role of oxidative defense and repair is the physiological function of TTase in the lens, we cloned the TTase gene and purified the recombinant human lens TTase. Although TTase required GSH for its activity, TTase was far more efficient in dethiolating lens proteins than GSH alone. It favored PSSG over PSSC and dethiolated gamma-crystallin-S-S-G better than the alpha-crystallin counterparts. Furthermore, TTase showed a remarkable resistance to oxidation (H2O2) in cultured rabbit lens epithelial cells when GSH peroxidase, GSH reductase, and glyceraldehyde-3-phosphate dehydrogenase were severely inactivated. We further showed that activity loss in those SH sensitive enzymes could be attributed to S-thiolation, but reactivation via dethiolation could be attributed to TTase. We conclude that TTase can regulate and repair the thiols in lens proteins and enzymes through its dethiolase activity, thus contributing to the maintenance of the function of the lens.
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PMID:Thiol regulation in the lens. 1080 24

Glycation initiated changes in tissue proteins, which are triggered by the Schiff base formation between the sugar carbonyl and the protein -NH2, have been suggested to play an important role in the development of diabetes-related pathological changes such as the formation of cataracts. While the initial reaction takes place by the interaction of >C=O of the parent sugars with the -NH2 of proteins, reactive oxygen species (ROS) dependent generation of more reactive dicarbonyl derivatives from the oxidation of sugars also plays a significant role in these changes, altering the structural as well as functional properties of proteins. The purpose of this study was to examine whether the activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), catalase and superoxide dismutase (SOD) could be affected by the high levels of fructose prevalent in diabetic lenses. Incubation of the enzymes with this sugar led to a significant loss of their activities. GAPDH was inactivated within a day. This was followed by the inactivation of catalase (3-4 days) and SOD (6 days). The loss of the activities was prevented significantly by incorporation of pyruvate in the incubation mixture. The protective effect is ascribable to its ability to competitively inhibit glycation as well as to its ROS scavenging activity. Hence, it could play a significant role in the maintenance of lens physiology and cataract prevention.
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PMID:Fructose induced deactivation of antioxidant enzymes: preventive effect of pyruvate. 1082 18

Hyperglycaemia, triose phosphate decomposition and oxidation reactions generate reactive aldehydes in vivo. These compounds react non-enzymatically with protein side chains and N-terminal amino groups to give adducts and cross-links, and hence modified proteins. Previous studies have shown that free or protein-bound carbonyls inactivate glyceraldehyde-3-phosphate dehydrogenase with concomitant loss of thiol groups [Morgan, Dean and Davies (2002) Arch. Biochem. Biophys. 403, 259-269]. It was therefore hypothesized that modification of lysosomal cysteine proteases (and the structurally related enzyme papain) by free and protein-bound carbonyls may modulate the activity of these components of the cellular proteolytic machinery responsible for the removal of modified proteins and thereby contribute to a decreased removal of modified proteins from cells. It is shown that MGX (methylglyoxal), GO (glyoxal) and glycolaldehyde, but not hydroxyacetone and glucose, inhibit catB (cathepsin B), catL (cathepsin L) and catS (cathepsin S) activity in macrophage cell lysates, in a concentration-dependent manner. Protein-bound carbonyls produced similar inhibition with both cell lysates and intact macrophage cells. Inhibition was also observed with papain, with this paralleled by loss of the active site cysteine residue and formation of the adduct species S-carboxymethylcysteine, from GO, in a concentration-dependent manner. Inhibition of autolysis of papain by MGX, along with cross-link formation, was detected by SDS/PAGE. Treatment of papain and catS with the dialdehyde o-phthalaldehyde resulted in enzyme inactivation and an intra-molecular active site cysteine-lysine cross-link. These results demonstrate that reactive aldehydes inhibit cysteine proteases by modification of the active site cysteine residue. This process may contribute to the accumulation of modified proteins in tissues of people with diabetes and age-related pathologies, including atherosclerosis, cataract and Alzheimer's disease.
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PMID:Evidence for inactivation of cysteine proteases by reactive carbonyls via glycation of active site thiols. 1667 91

Differential expression of apoptotic genes has been demonstrated in selenite-induced cataract. Acetyl-l-carnitine (ALCAR) has been shown to prevent selenite cataractogenesis by maintaining lenticular antioxidant enzyme and redox system components at near normal levels and also by inhibiting lenticular calpain activity. The aim of the present experiment was to investigate the possibility that ALCAR also prevents selenite-induced cataractogenesis by regulating the expression of antioxidant (catalase) and apoptotic [caspase-3, early growth response protein-1 (EGR-1) and cytochrome c oxidase subunit I (COX-I)] genes. The experiment was conducted on 9-day-old Wistar rat pups, which were divided into normal, cataract-untreated and cataract-treated groups. Putative changes in gene expression in whole lenses removed from the rats were determined by measuring mRNA transcript levels of the four genes by RT-PCR analysis, using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal control. The expression of lenticular caspase-3 and EGR-1 genes appeared to be upregulated, as inferred by detecting increased mRNA transcript levels, while that of COX-I and catalase genes appeared to be downregulated (lowered mRNA transcript levels) in the lenses of cataract-untreated rats. However, in rats treated with ALCAR, the lenticular mRNA transcript levels were maintained at near normal (control) levels. These results suggest that ALCAR may prevent selenite-induced cataractogenesis by preventing abnormal expression of lenticular genes governing apoptosis.
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PMID:Regulatory effect of acetyl-l-carnitine on expression of lenticular antioxidant and apoptotic genes in selenite-induced cataract. 2006 79