Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this experiment was to determine the contribution of calpain proteolytic enzyme (EC 3.4.22.17) in the formation of nuclear cataract during lens culture in xylose. Increased lens calcium was found to be required for formation of xylose nuclear cataract in our culture system. Inhibition of calpain by the cysteine protease inhibitor E64 was effective in slowing the formation of nuclear cataract, even though lens calcium and hydration were markedly elevated. These results showed that hydration and elevated calcium alone do not produce xylose nuclear cataract, and they indicated that calpain proteolysis may be necessary for xylose nuclear cataract in the rat lens.
 ...
PMID:Hydration and elevated calcium alone do not produce xylose nuclear cataract: role of proteolysis by calpain. 160 94

Cataracts were produced in cultured rat lenses by either 10 microM calcium ionophore A23187, 25 microM sodium selenite, or 30 mM xylose. E64, an inhibitor of cysteine proteases, such as calpain (EC, 3.4.22.17), reduced severity of cataract and proteolysis of crystallins when included at a 500 microM concentration in the culture medium along with cataractogenic agents. Calpain II enzyme activity and the amount of calpain antigen were decreased in the cytosol of cataractous lens. However, E64 caused an increase in the amount of an 80-kD calpain subunit associated with the ethyleneglycol-bis-(beta-aminoethylether) tetraacetic acid/ethylenediaminetetraacetic acid-washed insoluble proteins when lenses were incubated with cataractous agents. These data indicate that E64 was at least partially effective in inhibiting lens calpain, and that activation of lens calpain may involve binding to the insoluble fraction. These results provide strong evidence for the activation of calpain in rodent cataracts and suggest testing inhibitors of calpain as anticataract drugs.
 ...
PMID:Amelioration of cataracts and proteolysis in cultured lenses by cysteine protease inhibitor E64. 184 10

The occurrence of chronic mucocutaneous candidiasis accompanying polyglandular autoimmune syndrome type I is reported in a female aged 13. Apart the candidiasis, since the age of 3, she had convulsions beginning at 6, cataract at 9, teeth abnormalities, and basal ganglia calcifications. Laboratory data confirmed the diagnosis of hypoparathyroidism. This picture was accompanied by intestinal malabsorption, leading to a state of progressive malnutrition, with intense hypoalbuminemia and anemia. Although the pathophysiology of malabsorption, in these cases, is still not clear, the therapeutic response to pancreatin, in the present case, suggested pancreatic insufficiency, reinforced by the normal d-xylose test and the small intestinal biopsy with inexpressive result.
 ...
PMID:[Polyglandular autoimmune type I syndrome with hypoparathyroidism, chronic mucocutaneous candidiasis and intestinal malabsorption]. 213 67

Eye MAO-A, MAO-B, semicarbazide-sensitive amine oxidase (SSAO) and aldehyde reductase (AR) activities were measured in young and old rats. When enzyme activity is expressed as nmol (mg protein)-1 min-1, a significant decrease (18-23%) of SSAO activity in the eye of old rats was found, whereas there was no significant difference in MAO-A and MAO-B activities. A significant increase of AR activity with D-xylose (67%), DL-glyceraldehyde (64%), D-glucuronate (43%) and D-glucose (21%) was found in the eye of old rats. These results suggest that changes in the activities of the amine metabolizing enzymes of rat eye with age might have consequences for their function in senescence; particularly, the increase of AR activity might be involved in cataract formation.
 ...
PMID:Age-related changes in the activities of the amine metabolizing enzymes of rat eye. 286 49

The isolated cultured rat lens has been used to examine the effects of the aldose reductase inhibitor sorbinil on lenticular polyol accumulation and sugar cataract formation. Lenses incubated in medium containing 35 mmol/L glucose accumulated sorbitol over a seven-day period without the appearance of overt opacities. Sorbitol accumulation was inhibited in a dose response fashion by sorbinil with an IC50 of 3.1 X 10(-6) mol/L. In lenses incubated in the presence of 29.5 mmol/L xylose, xylitol accumulation was accompanied by an increase in the water content of the lens and the development of a classical sugar cataract. All of these effects could be prevented by the addition of sorbinil to the culture medium. Complete inhibition of cataract formation required greater than an 80% inhibition of the xylitol accumulation. Reversal of a preformed xylose cataract by sorbinil could be achieved if the inhibitor was added at the stage of cortical opacities (20 h). Cataract progression proceeded normally over the next 48 hours and then the lens slowly began to clear. The rate of the reversal was dependent on the dose of sorbinil.
 ...
PMID:Effects of the aldose reductase inhibitor sorbinil on the isolated cultured rat lens. 308 8

To confirm the effect of a new aldose reductase inhibitor (ARI), rat lenses were cultured with xylose. ARI prevented opacities and reduced lens hydration caused by xylose. Next, cataract was produced by feeding a diet containing 50% galactose. ARI was tested for amelioration of cataract. On day 19 after feeding of galactose, nuclear cataracts were visible in 75% of the animals receiving only galactose, while nuclear cataracts were not observed in animals treated with ARI. In galactose cataract, lens hydration and calcium were significantly increased. Calpain in soluble and insoluble fractions was decreased. Alpha- and beta-crystallins were proteolyzed. These changes were inhibited by administration of ARI. These results suggested that proteolysis by calpain is an underlying mechanism in formation of sugar cataract in rat lens.
 ...
PMID:Proteolysis by calpain is an underlying mechanism for formation of sugar cataract in rat lens. 772 Apr 3

Aldose reductase (AR) is implicated in the pathogenesis of the diabetic complications and osmotic cataract. AR has been identified as an osmoregulatory protein, at least in the renal medulla. An outstanding question relates to the response of AR gene expression to diet-induced galactosemia in extrarenal tissues. This paper shows that AR gene expression in different tissues is regulated by a complex multifactorial mechanism. Galactose feeding in the rat is associated with a complex and, on occasions, multiphasic pattern of changes in AR mRNA levels in kidney, testis, skeletal muscle, and brain. These changes are not in synchrony with the temporal sequence of changes in tissue galactitol, galactose, and myoinositol concentrations. Moreover, galactose feeding results in changes in tissue AR activities that are not related, temporally or quantitatively, to the alterations in tissue AR mRNA or galactitol levels. It is concluded that AR gene expression and tissue AR activities are regulated by mechanisms that are not purely dependent on nonspecific alterations in intracellular metabolite concentrations. This conclusion is supported by the finding that chronic xylose feeding, despite being associated with intracellular xylitol accumulation, does not result in alterations in AR mRNA levels, at least in the kidney.
 ...
PMID:Effects of galactose feeding on aldose reductase gene expression. 832 80

Accumulation of sorbitol and xylitol in rat lenses incubated in medium-199 with and without verapamil has been studied. This antihypertensive drug, known to attenuate hypertension by its calcium channel blocking effect, is also known to inhibit cataract formation in diabetes. The present studies have demonstrated that verapamil's effect against cataract could also be partially related to its aldose reductase inhibitory activity, in addition to the Ca++ channel blocking activity. The accumulation of sorbitol in the lenses incubated with high glucose in the presence of 400 microM verapamil was only 2.3 mmoles/Kg wet weight against 11.3 mmoles/Kg in its absence. The level of xylitol attained in the presence of 10 mM xylose was 25.7 +/- 2.4 mmoles/Kg. It decreased to 4.8 +/- 1.2 mmoles/Kg in presence of 400 microM verapamil. Hence, verapamil is significantly effective in inhibiting lens aldose reductase dependent polyol synthesis, an action simultaneous with its effect on calcium penetration.
 ...
PMID:Inhibition of polyol formation in rat lens by verapamil. 857 16

Lenses from Rhesus monkeys were maintained in protein-free medium and both their biochemical and histological changes were examined. Lenses were dissected under a dissecting microscope to ensure minimal contamination by other ocular tissue, which allowed successful observation of whole lens morphology during culture. Lenses in culture showed no acute leakage of protein into medium, indicating that they had not been physically damaged during dissection. Cultured lenses remained transparent for 21 days without any noticeable histological changes. Even at 21 days of culture, 35S-methionine incorporation into lens protein was approximately 60% of the level observed in fresh lenses. The amounts of most protein species were rather constant in the lens capsule/epithelium throughout culture, but the amount of crystallins gradually decreased during the first 14 days, of culture due to selective decrease in crystallin synthesis. After day 14, both the amount of crystallins and their synthesis became stable. When 30 mM fructose, present in the control medium, was replaced with 30 mM xylose, lens opacification with some histological abnormalities such as vacuole formation was observed. In the xylose-induced cataract, the protein synthetic activity decreased dramatically. This system would be a valuable tool in investigating the mechanisms of lens homeostasis as well as mechanisms of cataractogenesis in primate lens.
 ...
PMID:Long-term maintenance of monkey lenses in organ culture: a potential model system for the study of human cataractogenesis. 894 49

Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a lens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H(2)O(2) or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H(2)O(2)-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate (3)H-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract.
 ...
PMID:Tempol-H inhibits opacification of lenses in organ culture. 1460 18


1 2 Next >>