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 purpose of this experiment was to assess the roles of free, intracellular calcium and calcium-dependent neutral protease (calpain II, EC.34.22.17) in selenite nuclear cataract. Free calcium ion concentrations within lens nuclear fibers during selenite cataractogenesis increased to 3 microM on day 2 post-injection (clear lens) and to 108 microM at day 4 (nuclear cataract). Calpain II is known to be activated in vitro by calcium levels above 50 microM. Calpain II activity was present in the lens nucleus at time periods preceding formation of selenite cataract. These data suggested that after selenite injection, calpain II was activated by elevated free calcium in the nucleus, and that calpain II-induced proteolysis of nuclear proteins was an important mechanism in selenite cataract. Calpain II levels were also observed to decrease in the nucleus during selenite cataractogenesis, probably due to autolysis. This was supported by the finding that incubation of purified lens calpain II with 100 microM calcium caused partial inactivation of the protease.
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PMID:Regional distribution of free calcium in selenite cataract: relation to calpain II. 282 Aug 91

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.
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PMID:Age-related changes of calpain II and alpha-crystallin in the lens of hereditary cataract (Nakano) mouse. 299 2

Calpain II (EC 3.4.22.17), a calcium-dependent neutral protease, was purified approximately 7000-fold from the soluble of rat lens. The estimated molecular weight of rat lens calpain II was 120,000, and the enzyme was composed of 80,000 and 28,000 MW subunits. Calpain II required 400 microM calcium, a reducing agent, and pH = 7.5 for maximal activity. The enzyme could not be activated by magnesium, and was inhibited by leupeptin and iodoacetate, but not by phenylmethylsulfonyl fluoride. Purified calpain II degraded rat alpha, beta H-, and beta L-crystallins, insoluble proteins, and intrinsic membrane proteins, gamma-Crystallin was not degraded. The proteolysis caused by purified calpain II was similar to proteolysis occurring during the formation of several experimental cataracts in rodents; this suggested that the enzyme may play a role in cataract formation.
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PMID:Purification of calpain II from rat lens and determination of endogenous substrates. 301 81

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.
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PMID:Origin of urea-soluble protein in the selenite cataract. Role of beta-crystallin proteolysis and calpain II. 303 41

The purpose of these experiments was to study the mechanism for precipitation of lens crystallins in cataract. An in vitro model was developed to activate the endogenous protease calpain II in the soluble proteins from young rat lens by addition of calcium in the presence of 120 mM KCl. Light-scattering, insoluble proteins were produced approximately 4-6 days after calpain II activation. Results showed that proteolysis was caused by activation of lens calpain II, proteolysis preceded precipitation by several days, and alpha-crystallin acted as a molecular chaperone against precipitation of crystallins caused by proteolysis. These data supported our hypothesis that calpain-induced proteolysis of the N-terminal arms of beta-crystallin polypeptides leads to a loss of normal oligomerization of beta-crystallin polypeptides and formation of abnormal insoluble aggregates, possibly stabilized by hydrophobic interactions.
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PMID:Precipitation of crystallins from young rat lens by endogenous calpain. 755 77

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.
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PMID:Proteolysis by calpain is an underlying mechanism for formation of sugar cataract in rat lens. 772 Apr 3

Lens epithelium from patients with cataract was obtained during surgery and frozen. The samples were subjected to SDS-electrophoresis and Western blotting. Calpains were quantified using polyclonal antibodies against m- and mu-Calpain could be detected but not the isoenzyme mu-calpain, indicating that m-calpain is the significant most important calpain in human lens epithelium. Quantification of m-calpain showed no relationship to age or gender, but there were significant differences between different types of cataract.
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PMID:Calpains in lens epithelium from patients with cataract. 782 81

Calpains (CANPs) are a family of calcium-dependent cysteine proteases under complex cellular regulation. By making selective limited proteolytic cleavages, they activate or alter the regulation of certain enzymes, including key protein kinases and phosphatases, and induce specific cytoskeletal rearrangements, accounting for their suspected involvement in intracellular signaling, vesicular trafficking, and structural stabilization. Calpain activity has been implicated in various aging phenomena, including cataract formation and erythrocyte senescence. Abnormal activation of the large stores of latent calpain in neurons induces cell injury and is believed to underlie neurodegeneration in excitotoxicity, Wallerian degeneration, and certain other neuropathologic states involving abnormal calcium influx. In Alzheimer's disease, we found the ratio of activated calpain I to its latent precursor isoform in neocortex to be threefold higher than that in normal individuals and those with Huntington's or Parkinson's disease. Immunoreactivity toward calpastatin, the endogenous inhibitor of calpain, was also markedly reduced in layers II-V of the neocortex in Alzheimer's disease. The excessive calpain system activation suggested by these findings represents a potential molecular basis for synaptic loss and neuronal cell death in the brain in Alzheimer's disease given the known destructive actions of calpain I and its preferential neuronal and synaptic localization. In surviving cells, persistent calpain activation may also contribute to neurofibrillary pathology and abnormal amyloid precursor protein trafficking/processing through its known actions on protein kinases and the membrane skeleton. The degree of abnormal calpain activation in the brain in Alzheimer's disease strongly correlated with the extent of decline in levels of secreted amyloid precursor protein in brain. Cytoskeletal proteins that are normally good calpain substrates become relatively calpain resistant when they are hyperphosphorylated, which may contribute to their accumulation in neurofibrillary tangles. As a major effector of calcium signals, calpain activity may mirror disturbances in calcium homeostasis and mediate important pathologic consequences of such disturbances.
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PMID:Calcium-activated neutral proteinase (calpain) system in aging and Alzheimer's disease. 784 93

Increasing evidence now suggests that excessive activation of the Ca(2+)-dependent protease calpain could play a key or contributory role in the pathology of a variety of disorders, including cerebral ischaemia, cataract, myocardial ischaemia, muscular dystrophy and platelet aggregation. In this review, Kevin Wang and Po-Wai Yuen discuss the evidence linking these disorders to calpain overactivation. At present, it is difficult to confirm the exact role of calpain in these disorders because of the lack of potent, selective and cell-permeable calpain inhibitors. However, given the multiple therapeutic indications for calpain, it appears that achievement of selective calpain inhibition is an important pharmacological goal.
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PMID:Calpain inhibition: an overview of its therapeutic potential. 785 6

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.
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PMID:Role of calpain in hydrogen peroxide induced cataract. 831 93


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