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)

This paper presents an overview of the current state of our knowledge concerning the metabolism and function of glutathione (GSH) in the lens, with particular reference to the contributions of Dr Jin H. Kinoshita to this field. Glutathione in the lens is synthesized from its constituent amino acids and degraded by mechanisms involving transpeptidation and hydrolysis. The turnover of GSH in the lens is due to its catabolism rather than transport of GSSG as is the case in red blood cells and some other tissues. Three aspects of the functional role of GSH in cataract formation are considered. First, GSH may be important in maintaining protein thiols in the reduced state, thus preventing the formation of high molecular weight protein aggregates which are the basis for light scattering and lens opacification. A second function may be to protect membrane -SH groups that are important in cation transport and permeability. A third functional role is to detoxify hydrogen peroxide and other organoperoxides. The glutathione redox cycle is intimately involved in the detoxification of H2O2 which is normally present in the aqueous humor.
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PMID:Glutathione and its function in the lens--an overview. 219 12

In this study we have investigated the oxidative metabolism of red cells (RBC), plasma, serum and aqueous humour of healthy subjects and of age-matched cataractous patients with and without chronic renal failure (CRF). Reduced glutathione (GSH) levels in RBC were lower in CRF patients than in the other groups. Oxidized glutathione (GSSG) plasma levels in CRF patients were higher than those of controls and cataractous subjects. The activity of the enzyme glucose-6-phosphate dehydrogenase in RBC was significantly reduced in CRF patients with respect to the other two groups. The levels of malondialdehyde (MDA) in RBC and in lens were about twice in CRF patients compared with the other two groups. The plasma levels of vitamin E were diminished in CRF patients; on the contrary, the biological liquid oxidant activity (BLOA) of serum in CRF patients was significantly higher than in controls and in cataractous patients without CRF. Cataractous patients with and without CRF showed similar levels of GSH in aqueous humour; on the contrary, the content of GSSG was significantly higher in CRF patients. Our findings seem to demonstrate that CRF patients are exposed to oxidative stresses that could probably act synergistically with uraemia and carbamylation of lens proteins. This synergism could explain why CRF represents a relatively high risk factor for cataract.
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PMID:Systemic human diseases as oxidative risk factors in cataractogenesis. II. Chronic renal failure. 226 73

The study has examined the effects of the SH-oxidizing agent diamide (Diazane dicarboxylic acid bis-(N,N-dimethyl-amide)) on the water-soluble portion of proteins from rabbit lenses. The dialyzed protein extracts were incubated for 1-1.5 hrs with various concentrations of diamide. Treatments were monitored for alterations in sulphydryl contents, gel filtration and gel electrophoresis profiles of proteins. The response to 2 mM diamide treatment for 1 hr consists of rapid oxidation (up to 40%) of protein-bound sulphydryl groups accompanied by an appearance of polypeptides with apparent molecular weights. The protein with molecular weight of 29 kilodaltons was shown to be involved in cross-linking. The linkages in the dialyzed water-soluble lens polypeptide fraction induced by diamide may be reduced by GSH (10 mM) treatment of protein extract. The main target of oxidative insult induced by diamide in the water-soluble proteins of the lens is probably the superficially localized sulphydryl groups of crystallins. Our observations suggest that the described oxidative system of proteins may be a useful tool for cataract research.
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PMID:[Oligomerization of water soluble proteins of rabbit crystalline lens under the action of diamide]. 226 11

Clinicopathological studies were performed on 156 lenses of human senile cataract obtained by cataract operations between 1970 and 1988. It became clear that the aging influences the functional destruction of the equatorial region, the pathological changes of the bow area, and changes of the extralens environment. After operation for the atrophic type of the posterior subcapsular cataract, aftercataract easily develops on the intraocular lens and this requires treatment. Long-term observations were carried out in 180 Wistar male rats under the same laboratory condition and histological studies were performed. The similarities between the senile Wistar rat cataract and the human senile cataract indicate that the Wistar rat cataract is useful as a model for studying the human senile cataract. These rats were initially classified into six groups (control, vitamin E diet, EPC eye drops, catalin eye drops and reduced catalin eye drops). To study the effects of the agents (vitamin E, ARI, EPC, catalin, reduced catalin) on the cataract in senile Wistar rats the mean cell density of lens epithelia were measured at 2 or 3-month intervals. There were no statistically significant differences in treated groups and the control group. The results suggest that these agents affect another factor of lens apart from the proliferative activity of lens epithelial cell. Effects of anti-cataract agents were investigated using cultured lens epithelial cells. When cultured rat lens epithelial cells were incubated in medium containing selenite, super-oxide dismutase (SOD) activity and GSH in the cells markedly decreased, and GSSG was markedly increased. When cultured rabbit lens epithelial cells were incubated in medium contained selenite and glutathione, SOD activity was maintained normal level. When cultured lens epithelial cells were incubated in medium contained selenite and pirenoxin, SOD activity also maintained a normal level. These results suggest that both glutathione and pirenoxin are effective as anti-cataract agents. Cataracts in spontaneously hypertensive rats (SHR) was investigated on male of Wistar-Kyoto rats (WKY), stroke resistant SHR (SHRSR) and stroke-prone SHR (SHRSP) rats aged 3 to 9 months. Cataracts in these rats were classified as follows: Type 0: no opaciiy, Type 1: nuclear opacity, Type 2: posterior subcapsular opacity, Type 3: nuclear opacity associated posterior subcapsular opacity and Type 4: complete opacity in both lenses. Incidence of cataract in WKY was 2.6%, SHRSR, 76.8% ant SHRSP, 88.2%. Incidence of nuclear opacity was remarkably higher in SHRSP (48.5%). In SHR aged from 3 to 5 months, nuclear opacity was ahead of the appearance of posterior subcapsular opacity which was increased during aging.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cataract--clinic and pathology]. 227 35

Protein-thiol mixed disulfides in lenses have been implicated in the mechanism of protein-protein disulfide and other cross-linking leading to protein aggregation. The methodology for the detection and quantitation of protein-thiol mixed disulfides has been successfully established in our laboratory. Examination of mixed disulfides at different stages during development of a cataract may give relevant information on the mechanism of cataractogenesis, and whether oxidation is a part of that mechanism. In this study we investigated the involvement of mixed disulfides in cataract formation by using the H2O2-exposed lens as a model. Rat lenses, after being exposed to 0.5 mM H2O2 in culture showed an inverse relationship between the GSH loss and the protein-GSH formation with no effect on the protein-cysteine level. The H2O2-induced protein modification was also demonstrated indirectly by isoelectric focusing. The rate of protein-GSH production is dependent on the time of exposure and the concentration of H2O2. Age also plays some role as the lens GSH level decreases and the protein-thiol mixed disulfides increase as the animal becomes older. Lenses of older rats did not display more susceptibility to H2O2-induced mixed disulfide formation. The two protein-thiol mixed disulfides have a well-defined pattern of distribution in the rat lens. Most of the protein-GSH was found in the cortex and the water-soluble protein fraction whereas more protein-cysteine was found in the nucleus and water-insoluble protein fraction. Lens of older rat has more protein-cysteine as well as more water-insoluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of protein-thiol mixed disulfides in cataractogenesis. 237 74

When 0.25 mumol of hydrocortisone succinate sodium (HC) was administered to 15-day-old fertile eggs, almost all lenses of chick embryos treated with HC for 48 hr were classified as cataract stage IV-V (95%). A triple application of potassium pyrroloquinoline quinone (PQQ) (1.25 mumol/egg) at 3, 10 and 20 hr after HC treatment showed a preventive effect against the HC-induced cataract formation (I:45%, II:25%, III: 30%). PQQ also prevented the decline of GSH in the lens caused by HC. The decline of GSH in liver 24 hr after HC administration was prevented by PQQ. These data indicate that PQQ can modify HC-induced effects and that the preventive effect of PQQ against HC-induced decline of hepatic GSH seemed to influence HC-induced events in lens.
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PMID:Preventive effects of pyrroloquinoline quinone on formation of cataract and decline of lenticular and hepatic glutathione of developing chick embryo after glucocorticoid treatment. 254 18

Fluorescence of intact lenses of F1 (CBA x C57BL6) mice at different stages of X-ray cataract induced by gamma irradiation (5.00 Gr) has been studied by synchronous scanning of fluorescence, the shift between emission and excitation wave lengths being 20 nm. The ratio between peek intensities of the nontryptophan and tryptophan fluorescence within the synchronous scanning spectra (K) has increased 3.5 times as much at the stage of singular dot-like opacities. K-parameter correlated with GSH level in the lenses (r = -0.9). According to the results achieved, K could be regarded as an informative indicator of the development of X-ray cataract at the stage previous to turbidity.
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PMID:[The fluorescence of mouse crystalline lenses at different stages of radiation cataract studied by synchronous scanning]. 265 53

The polycyclic aromatic hydrocarbon naphthalene is bioactivated by cytochromes P450 to an electrophilic epoxide intermediate, which subsequently is metabolized to naphthoquinones (NQ) and possibly to a free radical intermediate. These reactive intermediates may bind covalently to lenticular tissues, cause oxidant stress and/or lipid peroxidation, thereby initiating cataracts. To evaluate this hypothesis, male C57BL/6 or DBA/2 mice were treated with naphthalene or one of several naphthoquinone and naphthol metabolites, in the presence or absence of modulators of chemical bioactivation and detoxification. In C57BL/6 mice, cataracts were caused by naphthalene (500-2000 mg/kg ip) in a dose-dependent fashion. The incidence of naphthalene-induced cataracts was decreased by pretreatment with the P450 inhibitors SKF 525A and metyrapone, the antioxidants caffeic acid and vitamin E, the glutathione (GSH) precursor N-acetylcysteine, and the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (p less than 0.05). Naphthalene cataractogenicity was enhanced by pretreatment with the cytochrome P450 inducer phenobarbital and the GSH depletor diethyl maleate (DEM) (p less than 0.05), and was unaffected by pretreatment with the prostaglandin synthetase inhibitors aspirin or naproxen, or the epoxide hydrolase inhibitor trichloropropene oxide. Cataracts were initiated by 1,2-NQ and 1,4-NQ (5-250 mg/kg ip) in a dose-dependent fashion, with a molar potency about 10-fold higher than that for naphthalene. NQ cataractogenicity was enhanced by pretreatment with DEM (p less than 0.05). 1-Naphthol (56 to 562 mg/kg ip) demonstrated a cataractogenic potency intermediary to that for naphthalene and NQ. DBA/2 mice treated with naphthalene (2000 mg/kg ip), 1,4-NQ (65-250 mg/kg ip), 1,2-NQ (30-250 mg/kg ip), or DEM followed by 1,4-NQ (125 mg/kg ip) did not develop cataracts. These results suggest that naphthalene cataractogenesis in C57BL/6 mice requires P450-catalyzed bioactivation to a reactive intermediate, which may be the NQ and/or a free radical derivative, either of which is dependent upon GSH for detoxification.
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PMID:In vivo murine studies on the biochemical mechanism of naphthalene cataractogenesis. 274 33

The effect of vitamin E-containing liposome on experimental sugar cataract formation in vitro was investigated. The lenses of male Wistar rats aged 6 weeks were prepared by incubating with 55. 6 mM glucose with vitamin E-containing liposome (dipalmitoyl phosphatidylcholine: DPPC). We examined the formation of lens opacity and assayed vitamin E and its related compounds. Incubation with vitamin E-containing liposome prevented sugar cataract formation. In Addition, vitamin E concentration in lens was significantly elevated by incubation with vitamin E-containing liposome. In lenses of the high level glucose group incubated without vitamin E-containing liposome, lipid peroxide (LPO) content was increased, but in lenses of the high-level glucose group incubated with vitamin E-containing liposome the increase was significantly inhibited at each incubation time. Vitamin E had no effect either on the decrease of reduced glutathione (GSH) or the increase of sorbitol content in lens incubated with high level glucose medium. In conclusion vitamin E-containing liposome was transported from medium to lens well and was significantly effective in preventing experimental sugar cataract formation in vitro. The protective effects of vitamin E are probably caused not only by its antioxidative action.
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PMID:[Effect of vitamin E-containing liposome on experimental sugar cataract]. 275 Jun 6

Cataract is a long-term complication of diabetes mellitus. Diabetics have increased glucosamine levels and it is possible that the non-enzymic glycosylation of the lens structural proteins by glucosamine induces conformational changes in the lens that contribute to cataract formation. Aspirin and aspirin-like analgesics may protect against glycosylation. In this paper the binding of glucosamine to bovine lens proteins and the effects of aspirin, paracetamol and ibuprofen on this reaction were investigated. Significant binding of glucosamine to the lens proteins was found. Gel-chromatography indicated that beta H-crystallin was most reactive to the amino-sugar. Of the analgesics studied, aspirin was the most effective inhibitor of glycosylation, followed by the other anti-inflammatory drug, ibuprofen. Preincubation of the lens homogenate with aspirin was no more effective at decreasing binding of glucosamine than was simultaneous incubation with aspirin. Glutathione significantly inhibited glucosamine binding. Glucosamine is active in non-enzymic glycosylation but the reaction can be inhibited by agents thought to protect against cataract.
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PMID:The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. 275 89


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