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)

beta-Crystallins (beta 1-, beta 2- and beta 3-crystallin) comprise nearly half the protein of the human lens. The effect of near-UV radiation, which is one of the possible risk factors in cataract formation, on the beta-crystallins is investigated in this study. Protein intersubunit crosslinking, change in charge of the protein subunits to more acidic species and changes in protein tertiary structure (conformation) by 300 nm irradiation are reported. The fluorescence yield of protein tryptophan residues decreases by 300 nm irradiation. There is an increase in nontryptophan fluorescence (lambda cx 340 nm, lambda cm 400-600 nm), and in protein absorption at 340 nm, due to the formation of tryptophan photooxidation products. Both tryptophan and its oxidation products can be photoexcited by 300 nm irradiation and the latter are known to be good photosensitizers. The results provide evidence for the generation of H2O2 in the irradiated human beta-crystallin solutions by the Type I photosensitizing action of the chromophores absorbing at 300 nm. The H2O2 is generated via the intermediate production of O2 anion; the latter spontaneously dismutates to H2O2, presumably via O2- protein interactions. The amount of H2O2 generated per absorbed photon is compared for various solutions of beta 1-, beta 2- and beta 3-crystallins from human lenses of different age.
 ...
PMID:The effects of near-UV radiation on human lens beta-crystallins: protein structural changes and the production of O2- and H2O2. 276 85

Changes in lens proteins induced at the early stages of cataractogenesis in cac (Nakano) mice were investigated by two-dimensional gel electrophoresis (2D-PAGE). The 2D-PAGE profile of lens proteins in 21-day-old cac mice differed from that in 27-day-old normal mice, even though the appearance of 'pin-head' nuclear opacity (26-day-old) had not yet been observed in the lenses. Especially noticeable were great differences in the polypeptides associated with the alpha- and beta- crystallin subfractions, the appearances of which corresponded to an increase in a ratio of the amounts of Na+ to that of K+ in the lenses of defective mice. No dramatic decrease in the gamma-crystallin fraction was observed until the mature cataract stage.
 ...
PMID:Changes in lens proteins induced at the early stage of cataractogenesis in cac (Nakano) mice. 280 24

The ability of 2,6-dimethoxyquinone (DMQ) to impair 86Rb uptake by bovine lens epithelial cells was found to be independent of exogenous ascorbate in contrast to the impairment induced by Fe/Cu or riboflavin plus light. The cytotoxicity was associated with an electron spin resonance (ESR) detectable singlet radical (g = 2.0062) which also formed on incubation of DMQ with glutathione (GSH) or gamma-crystallin in vitro. Formation of the stable free radical appeared to require conjugation of DMQ by peptidyl thiol and required transition metal catalysis. A structure for the DMQ-glutathione free radical conjugate is proposed. Redox activity of quinone conjugates is suggested to be of relevance to an oxidative damage hypothesis of cataract.
 ...
PMID:Pro-oxidant activation of ocular reductants. 2. Lens epithelial cell cytotoxicity of a dietary quinone is associated with a stable free radical formed with glutathione in vitro. 282 94

The possibility that defects in lenticular proteins are one cause of hereditary cataract is discussed. Possible mutant loci for such proteins can be detected by linkage to restriction fragment length polymorphisms within or around these loci. In a family in which a Coppock cataract occurs, close linkage between the locus for this cataract and the gamma-crystallin gene cluster was found. The restriction fragment length polymorphism within the gamma-crystallin gene family is sufficiently informative to allow prenatal diagnosis of this disease within this family.
 ...
PMID:Hereditary cataract. Perspective for prenatal screening. 288 56

The age-related changes of calpain II (high-Ca2+-requiring form of Ca2+-dependent cysteine proteinase; EC 3.4.22.17) and alpha-crystallin in the lens of hereditary cataract (Nakano; cac/cac) mouse were studied. Before the onset of the cataract formation, i.e., at the end of the 2nd week after birth, the calpain activity in Nakano mice was as high as that in the control ICR mice, but it decreased rapidly as the cataract progressed to completion during the 4th and the 12th week. Marked degradation of lens proteins ensued between the 2nd and the 4th weeks, and one of these proteins was identified, using monospecific antibodies, as B chain of alpha-crystallin. A chain of alpha-crystallin was not degraded in vivo, in contrast to its known susceptibility to calpain in vitro. The present data suggest that in Nakano mice, calpain may be involved in the onset or early stage of the cataract formation.
 ...
PMID:Age-related changes of calpain II and alpha-crystallin in the lens of hereditary cataract (Nakano) mouse. 299 2

Within the human gamma-crystallin gene cluster polymorphic Taq I sites are present. These give rise to three sets of allelic fragments from the gamma-crystallin genes. Together these restriction fragment length polymorphisms define eight possible haplotypes, three of which (Q, R, and S) were found in the Dutch and English population. A fourth haplotype (P) was detected within a family in which a hereditary Coppock-like cataract of the embryonic lens nucleus occurs in heterozygotes. Haplotype P was found only in family members who suffered from cataract, and all family members who suffered from cataract had haplotype P. The absolute correlation between the presence of haplotype P and cataract within this family shows that the gamma-crystallin gene cluster and the locus for the Coppock-like cataract are closely linked [logarithm of odds (lod) score of 7.58 at its maximum at phi = 0]. This linkage provides genetic evidence that the primary cause of a cataract in humans could possibly be a lesion in a crystallin gene.
 ...
PMID:A locus for a human hereditary cataract is closely linked to the gamma-crystallin gene family. 302 77

Nuclear cataract resulting from an overdose of selenite was characterized by a five-fold increase in nuclear urea-soluble protein. The origin of this urea-soluble protein was examined by two-dimensional electrophoresis, immunoblotting with monospecific antisera against rat lens crystallins, and tryptic mapping. Cataractous urea-soluble protein was primarily composed of insolubilized beta- and gamma-crystallin polypeptides. Polypeptides from cataractous urea-soluble protein, and normal beta L-crystallin aggregates were compared by tryptic mapping. Approximately 19% of the urea-soluble protein from opaque nuclei was composed of 24.7 and 24.0 K polypeptides derived by limited proteolysis of 26.5 K beta L-crystallin polypeptide. Incubation of 26.5 K beta-crystallin polypeptide with purified rat lens calpain II in vitro caused production of fragments with similar molecular weights to polypeptides found in cataractous lenses. These results support the hypothesis that proteolysis may contribute to formation of urea-soluble protein in selenite cataract.
 ...
PMID:Origin of urea-soluble protein in the selenite cataract. Role of beta-crystallin proteolysis and calpain II. 303 41

A long-term system of organ culture for bovine lenses was used to investigate the effect of osmotic stress on lens opacification and crystallin loss. Lenses were pre-incubated in control medium containing L-[U-14C]tyrosine so that labelled crystallins were produced. The fate of these crystallins was studied in relation to two forms of osmotic stress. The addition of either ouabain or EGTA to the medium induced severe osmotic swelling and disturbance of the lens monovalent cation balance, but only the former treatment was followed by an increase in lens calcium. The changes due to osmotic stress were accompanied by loss of transparency and protein only in the lenses with increased calcium. Both opacification and increased calcium were found largely to be confined to the outer cortical fibres. Protein loss increased with time as lens calcium continued to increase. The protein recovered from the incubation medium was characterized by gel filtration and immunological techniques. The first protein detected was beta L-crystallin, and this formed the major part of the lost protein throughout, although alpha- and gamma-crystallins were detected at a later stage. Increased calcium also resulted in a change in the susceptibility of the crystallins to aggregation, since there was an increase in [14C]tyrosine incorporated into the lens high-molecular-weight (HM) fraction after exposure to ouabain, but not after exposure to EGTA. The relevance of these findings to human cataract is discussed.
 ...
PMID:Calcium-induced opacification and loss of protein in the organ-cultured bovine lens. 308 64

The authors studied a four-generation family with autosomal dominant congenital cataracts (ADCCs) using linkage analysis with 23 polymorphic phenotypic markers and DNA restriction fragment length polymorphisms (RFLPs) detected by lens-specific DNA probes. A total of 19 family members were studied and the ten affected members had embryonal lens opacities. Close linkage was rejected with DNA probes encoding beta-crystallin, gamma-crystallin, and the major intrinsic protein of the lens fiber membrane (MIP) excluding defects of these genes as the cause of the cataract in this family. No statistically significant lod scores were produced with the polymorphic phenotypic markers. These results support the genetic heterogeneity of ADCCs.
 ...
PMID:Genetic linkage analysis of autosomal dominant congenital cataracts with lens-specific DNA probes and polymorphic phenotypic markers. 317 13

The beta-crystallin basic principal polypeptide (beta Bp) appears to be altered in the lens of the Philly mouse and may be the main defect in this hereditary cataract. Northern blot analysis showed that an mRNA encoding for beta Bp is present in the Philly mouse lens, but normal beta Bp could not be detected. Instead, a different protein related to beta Bp has been observed. Western blot analysis with antibodies against specific beta Bp peptide sequences showed that the Philly protein shares the same amino-terminal residue as beta Bp but lacks a part of the carboxyl-terminal half of normal beta Bp. The altered protein is slightly smaller than beta Bp and has a more acidic isoelectric point by two-dimensional gel electrophoresis. It also lacks the property of heat stability characteristic of normal beta Bp. The mapping of the alteration in beta Bp may give insight into the nature of the heat stability of this protein as well as some indication of the structural components that are necessary to maintain optical clarity in the lens.
 ...
PMID:Alteration of a developmentally regulated, heat-stable polypeptide in the lens of the Philly mouse. Implications for cataract formation. 319 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>