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 reagent 2, 4, 6-trinitrobenzenesulfonic acid was used to probe the status of protein amino groups in the nuclei of control (cortical cataract) and advanced senile nuclear cataractous lenses. There was no significant difference in the content of reactive amino groups in control and senile nuclear cataractous lenses. The great majority, if not all, of the epsilon-amino groups of lysine residues in lens protein exist in the free form. There was no detectable difference in the protein sulfhydryl content of control and advanced senile nuclear cataractous lens proteins after reduction with mercaptoethanol.
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PMID:Availability of protein amino groups in senile nuclear cataract. 640 54

Bendazac, as such or in the form of its l-lysine salt, has a protective effect against lens protein denaturation both in vitro and in vivo. In vitro this effect has been documented on the lens proteins of rats, rabbits and pigs by using nephelometry, electrophoresis and electron microscopy. In vivo the protective effect has been observed after treatments ranging in duration from 3 to 14 days depending on the dosage used; the minimal effective dose produced a serum level of 35 micrograms/ml of bendazac. The penetration of the drug into the lens has been shown by both radioassay and HPLC; the lens concentration of bendazac increases with the duration of treatment. The mechanism of the protective action of bendazac against lens protein denaturation is discussed together with the implications of such protective action in the treatment of cataract.
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PMID:Basic data supporting the use of the l-lysine salt of bendazac in cataract. 661 87

Free amino groups were analyzed in the water-insoluble fraction (WIF) of cataractous human lenses of the nuclear sclerosis, pigmented type. Two modified versions of the trinitrobenzene sulfonic acid (TNBS) procedure for the determination of free amino groups in proteins (AFSA Habeeb, Anal Biochem 14:328-336, 1966) were used for this purpose. The concentration of free amino groups in WIF was found to be inversely related to the dry weight of this fraction. Taking WIF weight as a measure of the severity of nuclear cataract, it can be thus said that a relative loss of free amino groups apparently occurs during the insolubilization process associated to this type of senile cataract. The disappearance rate has been estimated as about 0.9%--NH2 per 1 mg of material added to WIF. After considering other possible alternatives (loss of accessibility of amino groups to TNBS, dilution of amino groups by materials with a low primary amine content) we have interpreted this finding as most likely due to the postsynthetic blockade of lysine epsilon-amino functions in WIF proteins. The potential involvement of lysine residues in Schiff base formation is discussed within the context of current views of cataractogenesis. The reaction of lysine epsilon-NH2 with unidentified carbonyl compounds could represent a partial but quantitatively important mechanism of yellowing in nuclear cataracts.
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PMID:Loss of free amino groups in the water-insoluble fraction of nuclear senile cataracts. 688 6

Ascorbate (vitamin C) degradation products can undergo non-enzymatic glycation (Maillard reaction) with proteins to form highly crosslinked structures with brown pigmentation and characteristic fluorescence. Proteins in the body, especially the long-lived proteins develop similar changes during aging and diabetes. Several studies have shown excessive degradation of ascorbate in plasma in diabetes, and in ocular lens during aging and cataract formation. Recent studies have suggested that ascorbate degradation products-mediated glycation plays a role in lens pigmentation and cataract formation. However, the precise chemical nature of ascorbate-specific advanced glycation end-products are not known. Here, we report the purification and characterization of a glycation end-product derived from one of the major degradation products of ascorbate, L-threose. This compound was characterized to be 2-acetamido-6-(3-(1,2-dihydroxyethyl)-2-formyl-4-hydroxymethyl-1- pyrrolyl)hexanoic acid (formyl threosyl pyrrole or FTP) formed by the condensation of epsilon-amino group of lysine with two molecules of threose. Formation of FTP occurred rapidly in the incubation of threose and lysine and reached plateau level within a day. We have developed a sensitive assay for its quantification in proteins based on enzyme digestion followed by HPLC. Ribonuclease A and human lens crystallins incubated with L-threose showed time- and sugar concentration-dependent increases in FTP, reaching 8.2 and 2.48 nmol per mg protein, respectively after one week of incubation. Human plasma proteins showed a peak with identical retention time as that of purified FTP under two different HPLC conditions. FTP may be used as a sensitive marker to assess ascorbate-mediated protein glycation and modifications in aging and diabetes.
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PMID:Protein modification by the degradation products of ascorbate: formation of a novel pyrrole from the Maillard reaction of L-threose with proteins. 749 3

Cataract formation in diabetes may be via non-enzymic glycosylation (glycation) of lens proteins due to increased concentrations of sugars present in the lenses of diabetic patients. The objective of this project was to identify the site(s) of glycation of bovine gamma-II-crystallin by [14C]fructose. gamma-II-crystallin was isolated from soluble lens nucleus proteins by gel chromatography, followed by ion-exchange chromatography and was then glycated by incubation with [14C]fructose. Radioactively labelled gamma-II-crystallin was cleaved with trypsin. Affinity chromatography of the tryptic peptides gave a single main peak containing the majority of the radioactivity. This indicated that fructose had reacted at a single site on the protein. Amino acid analysis of this peptide showed it to contain only lysine and a trace amount of glycine. By relating the results of the amino acid analysis to the amino acid sequence of gamma-II-crystallin, it was concluded that the labelled peptide corresponded to the N-terminal dipeptide. The site of glycation of bovine gamma-II-crystallin by fructose was thereby identified as the alpha-NH2 group of the N-terminal glycine.
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PMID:Identification of the site of glycation of gamma-II-crystallin by (14C)-fructose. 820 63

The amino acid lysine has been reported to delay cataractogenesis by 'some unknown mechanism'. Lysine and glycine were found to react with glucose at physiological pH and temperature and undergo non-enzymic glycation. The formation of glycated lysine was shown by paper and thin-layer chromatography, HPLC and using an authentic sample of epsilon-fructosyl lysine. Confirmation was made by studies on incorporation of U-[14C]glucose into lysine and glycine. The extent of glycation of lysine was 15.5% in 96 hr and rose to 20% in 20 days. Lysine and glycine alone of varying concentrations lowered the extent of glycation of lens proteins significantly in glucose-treated homogenates of normal lens from humans and goats. Scavenging of intracellular glucose and thereby protecting the lens proteins from excessive glycation appears to be the mechanism of action by which lysine and glycine could exercise beneficial effect on cataract.
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PMID:Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis. 828 49

Acetylation of the lysines of bovine lens alpha A-crystallin has been examined after 0-48-hr incubations of whole alpha-crystallins in 100 mM aspirin. The alpha A-crystallins were isolated after the incubation, proteolytically digested into peptides which were separated by reversed phase HPLC and analysed by mass spectrometry. For the reaction conditions used in this investigation, acetylated lysyl residues were the principal products. The extent of acetylation was quantified from the intensities of the peaks in the fast atom bombardment mass spectra of the modified and unmodified peptides. The modified lysine containing peptides demonstrated that all seven lysyl residues of alpha A-crystallin reacted with aspirin; the extent of acetylation at each lysyl residue varied. Plots of the extent of acetylation vs. time were used to calculate rate constants for the reaction at each lysyl residue. The rate constant for the acetylation of Lys 166, the most reactive, was about seven times greater than for Lys 88, the least reactive. These rate constants were used to calculate the yield of predicted products for the reaction of alpha-crystallin with therapeutic concentrations of aspirin. Comparison of the yield of acetylated alpha-crystallin with the yield of carbamylated alpha-crystallin that might occur due to renal failure indicates that aspirin is not likely to be an effective inhibitor of cataract due to carbamylation of lysyl residues.
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PMID:The reaction of bovine lens alpha A-crystallin with aspirin. 840 69

The autoxidation and reactivity towards proteins of 3-hydroxykynurenine, a tryptophan metabolite found in the human lens, has been studied. At neutral pH, 3-hydroxykynurenine was readily oxidized using molecular oxygen with the formation of several coloured products. The autoxidation of both 3-hydroxykynurenine and the related aminophenol, 3-hydroxyanthranilic acid, was inhibited by the inclusion of sulphydryl compounds such as glutathione or cysteine. Covalent adducts involving the thiols were not observed with either aminophenol. 3-Hydroxykynurenine was found to react with proteins, including lens proteins, to produce brown-coloured polypeptides characterized by an indistinct long wavelength absorption. This protein tanning was inhibited by glutathione. Despite the presence of an amino group in the side chain of 3-hydroxykynurenine, this tanning of proteins was found to involve amino groups including those of lysine residues, as has been found for 3-hydroxyanthranilic acid. Although both aminophenols tanned polylysine, only 3-hydroxykynurenine induced precipitation of the polyamino acid. 3-Hydroxykynurenine tanned all of the purified crystallins but induced precipitation only in the case of alpha A-crystallin. The implications of these findings for senile cataract are discussed.
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PMID:The modification of proteins by 3-hydroxykynurenine. 840 81

Calf lens alpha-crystallin was isolated and the lysine residues were extensively modified with a variety of chemical agents. The effect of these modifications on elastase inhibitor activity, apparent molecular size, antibody reactivity and solubility were determined. The addition of either a methyl group or a threose residue did not alter the charge on the lysine residues and had little or no effect on either inhibitor activity or apparent molecular size. The introduction of a negative charge by either carboxymethylation or citraconylation caused a marked decrease in size and an almost complete loss of inhibitor activity. The introduction of a hydrophobic residue by reaction with either a trinitrobenzenesulfonic acid or Bolton Hunter reagent caused a slight increase in size, but a 70% increase in elastase inhibitor activity. Reaction with fluorescamine resulted in the dissociation of alpha-crystallin in a 200-kDa species, yet caused a two to four-fold increase in elastase inhibitor activity, which was similar to the activity of the water-insoluble fraction isolated from aged human lens and cataract. Several of these modified alpha-crystallins were compared for reactivity with a polyclonal alpha-crystallin antiserum using a quantitative slot blot assay. Charge neutral modifications resulted in a two to three-fold loss of antibody recognition, whereas the other preparations showed an almost complete loss of antigenic activity. None of the modifications caused the alpha-crystallin to precipitate at higher salt concentrations (0.3 M) with the exception of threose which caused a 30% decrease in soluble protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemical modification of alpha crystallin. 843 30

Uremia has been implicated in cataractogenesis due to protein carbamylation by cyanate derived from urea. The present study was designed to directly identify the effects of carbamylation on actin polymerization and the possible contribution to cataract formation. The susceptibility of actin to carbamylation is expected because of the 19 lysines distributed along its length. The lysines of actin were selectively carbamylated by methylisocyanate (MIC) at pH 8.0 and 4 degrees C and actin polymerization assayed by high-shear viscometry, fluorescence and transmission electron microscopy. Our results provide evidence that non-enzymatic carbamylation of the lysine residues prevents the polymerization of actin. In addition, this carbamylated actin inhibited the polymerization of nascent, unmodified actin. High-shear viscosity measurements demonstrated decreased initial apparent rates and decreased steady-states (final specific viscosities) of polymerization. Fluorescence measurements showed decreased relative intensities of fluorescence versus control and confirmed the inhibitory effects of carbamylation by MIC on the steady state of F-actin. Transmission electron microscopy (TEM) showed the presence of disorganized filaments when carbamylated actin was added to polymerizing unmodified actin. Our results suggest that carbamylation of actin can cause a loss of ordered filament structure and shape of the lens fiber cell, thus predisposing it to cataract development.
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PMID:Methylisocyanate and actin polymerization: the in vitro effects of carbamylation. 844 78


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