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 these experiments was to examine the relationship between oxidation cataract and proteolysis in cultured rat lens. Hydrogen peroxide cataract showed insolubilization of protein, loss of 31 kDa beta B1-crystallin polypeptide, decreases in soluble calpain, and increases in insoluble calpain. This suggested that calpain may be activated in hydrogen peroxide treated lenses, since beta B1 is a known calpain substrate, and calpain undergoes autolysis and degradation when activated. Furthermore, the cysteine protease inhibitor E64 was partially effective in preventing development of H2O2-cataract. E64 also prevented the loss of the 31 kDa beta B1-crystallin polypeptide and decreased the loss of calpain in the lens. These results suggested that development of hydrogen peroxide induced cataract in rat lenses was associated with activation of calpain.
 ...
PMID:Role of calpain in hydrogen peroxide induced cataract. 831 93

The aim of this study was to determine if the unusual coloured species characteristic of age-related nuclear cataract could be localised to specific residues of the crystallins. The insoluble, crosslinked and coloured cataract protein fraction (CPF) was isolated from cataract human lenses. Using a combination of tryptic digestion, gel filtration and multiple reversed phase high performance liquid chromatography (RP-HPLC), coloured peaks were isolated and subjected to amino acid sequence analysis. With these techniques, it was hoped to identify and locate the modified residues. Sequence information was obtained on 16 'coloured' peptides. Many of the peptides were found to be derived from alpha B-crystallin. When redundancies are taken into account, six distinctive peptides were found to be derived from alpha B-crystallin; one from beta B1-crystallin, two from beta A3/A1-crystallin and three from gamma S-crystallin. Three sites of possible crystallin residue isomerisation to modification were detected in the alpha B- and beta A3/beta A1-crystallins, including probable asp isomerisation at residues 25 and 36 in alpha B-crystallin. Since the CPF is unique to nuclear cataract lenses, these data suggest that alpha-crystallin, and alpha B-crystallin in particular, may be implicated in the cataract process. This finding supports that of a recent study on cataract proteins using pronase digestion [Chen YC, Reid GE, Simpson RJ, Truscott RJW. Exp Eye Res 1997;65:835.]
 ...
PMID:Evidence for the participation of alpha B-crystallin in human age-related nuclear cataract. 965 87

The purpose of these experiments was to determine if truncation and deamidation alter the structure of a human lens protein, beta B1-crystallin. Recombinant wild type and a deamidated form of recombinant beta B1 were expressed in Escherichia coli. Wild type beta B1 was also enzymatically cleaved to generate a physiologically-relevant truncated beta B1. Purity and size of the expressed proteins were confirmed by SDS-PAGE and electrospray ionization mass spectrometry. Size exclusion chromatography and light scattering were used to determine aggregation states of beta B1. Protein conformations were predicted from sedimentation velocity analysis. Molecular weights of 49,000 and 54,000 Da were obtained for wild type beta B1 by sedimentation equilibrium and light scattering, respectively. A sedimentation coefficient of 2.7 S was determined for wild type beta B1. Molecular weights of 54,000 and 60,000 Da were determined for deamidated beta B1 by sedimentation equilibrium and light scattering, respectively. However, deamidated beta B1 eluted earlier than wild type beta B1 on size exclusion chromatography, with an estimated molecular weight between 78,000 and 116,000 Da. Loss of the extensions of beta B1 caused abnormal association of the protein with the stationary phase during size exclusion chromatography. Wild type beta B1 was predicted to form a dimer with an elongated structure. The earlier elution of the deamidated beta B1 dimer on size exclusion chromatography suggested the dimer was less compact. Truncation caused abnormal column interactions suggesting an altered conformation. These changes are important because truncation and deamidation occur extensively in aging human lenses and may be important for senile cataract formation.
 ...
PMID:Deamidation of human beta B1 alters the elongated structure of the dimer. 1118 Sep 77

Cataract is a common cause of blindness and results from destruction of the microarchitecture of the lens. It is observed in many genetic syndromes, infections, inflammatory diseases and during aging. Fluctuations in lens density and light scattering by altered refraction index form the physical basis for this process, but the pathogenesis is poorly understood. Increased levels of gelatinase B/matrix metalloproteinase-9 have been reported for cataract-associated disorders such as eye inflammation and diabetes. We demonstrate that incubation of lenses with gelatinase B leads immediately to cataract. In complete eye extracts, betaB1 crystallin was identified as the major gelatinase B substrate by combination of proteomics, mass spectrometry, and Edman degradation analysis. The cleavage of betaB1 crystallin was also observed in vivo after endogenous gelatinase B-induction by the chemokine granulocyte chemotactic protein-2 in wild-type mice but not in gelatinase B-/- mice.
 ...
PMID:Gelatinase B/matrix metalloproteinase-9 provokes cataract by cleaving lens betaB1 crystallin. 1562 92

DeltaFosB is a truncated form of a FosB transcription factor, which is created by alternative splicing. Previous work has shown that transgenic mice expressing DeltaFosB both in the retina and in the lens developed a posterior subcapsular cataract resulting from the misalignment of the fibres in the suture region. In the previous study, it was not clear whether DeltaFosB expression was required in both tissues to produce the cataract. Therefore, DeltaFosB expression targeted to either the lens or the retina was undertaken in order to clarify the contribution of each tissue to cataract development. For lens expression, the R2betaB1DeltaFosB construct was synthesized (R2, an enhancer; betaB1, a chicken betaB1 crystallin gene promoter fragment). For the retina, RhoDeltaFosB was prepared. As a promoter, the bovine rhodopsin upstream region was used. DeltaFosB expression in heterozygote animals was monitored by Western blotting. Cataract development in heterozygotes of R2betaB1DeltaFosB transgenics and in both heterozygotes and homozygotes of RhoDeltaFosB transgenics was followed by slitlamp examination. The transgenic mice prepared with RhoDeltaFosB expressed DeltaFosB only in the retina and showed no sign of lens opacity. One line of the R2betaB1DeltaFosB transgenic was found to have expression only in the lens and developed posterior subcapsular cataract. We concluded that retinal expression of DeltaFosB is not sufficient to cause cataract while expression exclusively in the lens produces posterior subcapsular cataract.
 ...
PMID:DeltaFosB expression and cataract. 1564 31