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)

We used an animal model of hypocalcemic cataract to investigate the changes of the cation levels and the Ca2+ pump (Ca(2+)-ATPase) function in the lens. Wistar rats (4 weeks old) were fed with a low calcium and no vitamin D3 diet. After 4 weeks on this diet, anterior subcapsular cataract was recognized, when calcium concentration in the aqueous humor and serum had significantly decreased. Calcium content in the lens decreased and sodium content increased. Ca(2+)-ATPase activity detected by [gamma-32P] ATP assay did not show significant change. We concluded that cataract during the early stage of hypocalcemia is caused by membrane damage with low calcium level in the aqueous humor and sodium content increase in the lens. We also studied the ultracytochemical localization of Ca(2+)-ATPase activity and found it in the plasma membrane of the lens epithelium and cortex and also in the epithelium organelles.
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PMID:[Ca(2+)-ATPase activity in the hypocalcemic cataract]. 810 58

The lens has a very high content of UDP sugars. These are required for glycoprotein and proteoglycan synthesis, as components of fiber cell membranes and the capsule. In diabetes, changes in these sugar nucleotides are related to pathological changes in the basement membranes of cells from non-insulin-requiring tissues. We have investigated whether this is the case in the lens in diabetes and we report here that UDP-sugar levels are, in contrast to the norm in other non-insulin-requiring tissues, decreased at 2 and 4 weeks of diabetes. This is despite an elevation in the precursors of their formation, both of the pyrimidine (PPRibP) and carbohydrate (glucose, glucose 6-phosphate) components. Also reported here is the observation that lens pyrimidine biosynthesis occurs primarily by the de novo route, and that orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase are unchanged in diabetes. We have measured the energy charge of the adenine and uridine nucleotide pools and report both to be compromised under the diabetic condition. The fall in ATP provision is proposed to be responsible for the fall in UTP and hence leads to the recorded decrease in the UDP sugars. These changes are discussed in relation to the change in capsular and fiber cell composition and the functional significance of this in cataract formation.
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PMID:Changes in uridine nucleotides and uridine nucleotide sugars in diabetic rat lens: implications in membrane glycoprotein formation. 812 94

Previous work has demonstrated that photochemically induced oxidative stress generated with 4 microM riboflavin in a 4% oxygen atmosphere utilizing daylight type radiation is capable of causing cataract in cultured rat lenses. Such cataract is prevented by the GSH peroxidase type mimic, AL-3823A. Examination of the early stages of cataract formation produced by short-term oxidative stress and recovery is now reported. A 24-hr oxidative stress, under the above conditions, causes loss of transparency, particularly in the equatorial region, increased hydration, loss of glyceraldehyde-3-PO4 dehydrogenase activity, oxidation of non-protein thiol and a decrease in 86Rb and [14C]choline uptake and ATP levels. Examination of recovery of these parameters during a 72-hr period indicates, in most cases, little or no reversal of oxidative damage. Hydration and loss of non-protein thiol continued during the recovery period. The presence of AL-3823A during the stress period prevented change in all parameters. Transport systems appear to be particularly vulnerable to this type of oxidative stress losing 50% or more activity within 4 hr. Even after a 2-hr stress, choline transport did not recover even though, under these conditions, ATP levels had only decreased slightly. Cytosolic components such as non-protein thiol and glyceraldehyde-3-PO4 dehydrogenase also showed little change after a 4-hr insult. 86Rb efflux experiments indicated no change in permeability during a 24-hr stress period. The overall conclusion from these studies is that a 24-hr oxidative stress which appears to reflect physiological conditions existing during cataract development, causes extensive, irreversible damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prevention of cataract caused by oxidative stress in cultured rat lenses. II. Early effects of photochemical stress and recovery. 815 19

delta 1-pyrroline-5-carboxylate synthetase (P5CS) catalyzes the ATP and the NAD(P)H-dependent conversion of L-glutamate to glutamic gamma-semialdehyde (GSA) which is the metabolic precursor for proline biosynthesis. We cloned a human P5CS cDNA by database cloning strategy and sequenced 2,907 bp from this cDNA which has a closed open reading frame (ORF) of 2,385 bp coding for a polypeptide of 795 amino acid residues. This cDNA, as its plant counterpart, encodes a bifunctional enzyme, with both gamma-glutamyl kinase (gamma-GK) and gamma-glutamyl phosphate reductase (gamma-GPR) activities that catalyzes the first 2 steps in proline biosynthesis and it hybridizes to a 4.5 kb mRNA from various tissues. A human genetic disease caused by a deficient P5CS has been recognized. The phenotypic features for deficiency of P5CS include joint hyperlaxity, skin hyperelasticity, cataract and mental retardation with hyperammonemia and low plasma levels of proline, citrulline and ornithine.
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PMID:Database cloning human delta 1-pyrroline-5-carboxylate synthetase (P5CS) cDNA: a bifunctional enzyme catalyzing the first 2 steps in proline biosynthesis. 876 62

microPx-11, a ferriheme undecapeptide proteolytic degradation product of cytochrome C is shown to be a peroxidase with broad specificity degrading H2O2 and tertiary butyl hydroperoxide. It is also capable of effectively eliminating superoxide and hydroxyl radical. The peroxidase loses activity in the presence of peroxide unless it is stabilized by ascorbate (Asc) or solutions such as aqueous humor or medium 199. While thiol but not disulfides inactivates the microPx-11, it is not inhibited in the presence of the rat lens which has a high GSH content. microPx-11 at concentrations 10 to 50 fold greater than are required to achieve good protective activity exhibits no toxicity based on cell viability, ATP levels and lens transparency after long-term incubations of alpha TN4-1 cells or cultured rat lens. The peroxidase is capable of protecting cultured rat lenses from photochemical stress where H2O2, O2.- and OH. are generated based on transparency, choline transport, epithelial cell viability and protein integrity as indicated by SDS-PAGE of the rat lens protein. In the absence of the peroxidase, extensive epithelial cell death and other degradative changes are observed. The DNA of alpha TN4-1 cells can also be protected from H2O2 induced single strand breaks by the microPx-11. The overall results suggest that a number of cytochrome C proteolytic degradation products are peroxidases which may be effective anti-cataract agents protecting the lens from oxidative stress.
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PMID:Microperoxidases catalytically degrade reactive oxygen species and may be anti-cataract agents. 946 80

delta 1-pyrroline 5-carboxylate synthetase (P5C synthetase) catalyzes the ATP and the NAD(P)H-dependent conversion of L-glutamate to glutamate semialdehyde (GSA) which is the metabolic precursor for proline biosynthesis. We described in two siblings a paradoxical hyperammonemia with hypoprolinemia and hypoornithinemia associated to bilateral cataract, mental retardation, joint laxity and skin hyperelasticity. We cloned human P5C synthetase-cDNA by database cloning strategy: this cDNA has an open reading frame of 2,385 bases coding for a polypeptide of 795 amino acids. Both patients are homozygous for an L396S substitution, this amino acid being highly conserved across species. This is the first report of a P5C synthetase deficiency in human.
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PMID:[A new inherited metabolic disease: delta1-pyrroline 5-carboxylate synthetase deficiency]. 962 38

The concentration of taurine is high in the lens. However, its function therein remains unknown. Studies from other tissues suggest that in addition to several other modes of action, it acts as an antioxidant. We therefore hypothesize that taurine may be a part of the antioxidant defense mechanisms involved in protecting the lens against oxidative stress and consequent cataract formation. In these studies, the protective effect of taurine was examined using lens culture system with menadione as an oxidant. Inclusion of this compound in the incubation medium was found to have several adverse effects on the lens, such as a decrease in its ability to accumulate rubidium against a concentration gradient and fall in the levels of glutathione, ATP and an increase in water insoluble proteins. All these deleterious effects were attenuated significantly by addition of physiological amounts of taurine to the menadione-containing medium.
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PMID:Oxidative stress to rat lens in vitro: protection by taurine. 980 50

Data in the present paper demonstrate a significant inhibition in the progress of sugar cataract formation by systemic administration of pyruvate. The formation of the cataract was induced by feeding young rats a diet containing 30% galactose. All animals fed this diet developed nuclear lens opacity by the end of 30 days. This was delayed if the diet and water contained, in addition, 2% sodium pyruvate. The incidence of cataract in the latter group was 0% at day 30 and only 25% at day 55. Physiologically, the inhibition was associated with the prevention of lens membrane damage as reflected by its ability to maintain transport of rubidium ions against a concentration gradient; decreased tissue hydration as indexed by the lens wet weight; inhibition of protein glycation, and higher levels of ATP. Since pyruvate, being a normal tissue metabolite, is likely to be non-toxic, the findings are considered useful for further pharmacological studies with this and other similar metabolites, relevant to protection against various secondary complications of diabetes and galactosemia.
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PMID:Attenuation of galactose-induced cataract by pyruvate. 1023 Aug 4

The effects of lysophosphatidic acid (LPA), a bioactive phospholipid, on the response of the cytosolic free Ca2+ concentration ([Ca2+]i) to hypotonic stress were studied in cultured bovine lens epithelial cells, to test whether LPA affects cellular swelling-mediated increase in [Ca2+]i, which may relate to formation of sugar cataracts. Exposure of the cells to a 30% hypotonic stress caused only a slight increase in [Ca2+]i. Pretreatment with LPA (10 microM) significantly augmented the hypotonic stress-induced [Ca2+]i response, whereas addition of LPA to the cells did not affect [Ca2+]i. The hypotonic stress-induced increase in [Ca2+]i in the presence of LPA was inhibited by Gd3+, a blocker of mechanosensitive cation channels, but not by nicardipine, a L-type Ca2+ channel blocker, or thapsigargin, an inhibitor of endoplasmic reticulum-ATPase pump. These results show that LPA sensitizes the response to hypotonic stress via increase in Ca2+ influx through Gd3+-sensitive stretch-activated ion channels, and not via Ca2+ release from intracellular stores. On the other hand, LPA did not affect the [Ca2+]i response to ATP, a Ca2+ mobilizing agonist. Therefore, LPA sensitizes the hypotonic stress-induced [Ca2+]i response in lens epithelial cells, suggesting that LPA potentiates the development of cataracts induced by cellular swelling such as sugar cataract.
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PMID:Sensitizing effect of lysophosphatidic acid on Ca2+ response to hypotonic stress in cultured lens epithelial cells. 1044 15

Studies describe an attenuation of sugar cataract formation by topical administration of ethyl pyruvate. Cataract formation was induced by feeding young rats a 30% galactose diet. Mature cataracts appeared in about thirty days. Instillation of the eye drops containing 5% ethyl pyruvate decelerated the process significantly. Biochemically, the effect was reflected by lowering in the contents of dulcitol and glycated proteins. The ATP levels were also higher in comparison to the placebo treated group. The effects are hence attributable to the effect of pyruvate in inhibiting dulcitol synthesis and protein glycation, in addition to its antioxidant properties and metabolic support. The use of esterified pyruvate instead of the unesterified pyruvate was preferred because of its greater penetration through the cornea and consequently a higher concentration attained in the aqueous humor.
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PMID:Attenuation of sugar cataract by ethyl pyruvate. 1056 89


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