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)

Calpain I (mu-calpain) and II (m-calpain) are well known calcium-activated neutral cysteine proteases. Many reports have shown that activation of calpain is related to cataract formation, neuronal degeneration, blood clotting, ischemic injuries, muscular dystrophy and cornified cell envelope (CE) formation. Here, we report that insoluble CE formation was reduced after treatment with calpain I inhibitor (N-acetyl-leucyl-leucyl-norleucinal) on normal human epidermal keratinocytes (NHEK), whereas serine and thiol protease inhibitors had no effect on the reduction of CE. When NHEK cells were confluent, keratinocytes were treated with various concentrations (0.5 microM-0.5 mM) of calpain I inhibitor or serine and thiol protease inhibitors under calcium induced differentiation. Insoluble CE formation was reduced about 90% in the 50 microM calpain inhibitor I treated group by day 9 of culture, whereas insoluble CE was reduced only 10% in the same condition. Interestingly TGase activity was blocked by 90% in the 0.5 mM calpain inhibitor treated group within 72 h, whereas TGase activity was retained by 80% in the 0.5 mM serine protease inhibitor treated group at 7 day treatment. Therefore it can be suggested that cysteine protease calpains might be responsible for the activation of the TGase 1 enzyme to complete insoluble CE formation during epidermal differentiation.
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PMID:Calpain inhibitors reduce the cornified cell envelope formation by inhibiting proteolytic processing of transglutaminase 1. 989 58

Tissue transglutaminase has been identified as a contributor to a wide variety of diseases, including cataract formation and Celiac disease. Guinea pig tissue transglutaminase has a very broad substrate specificity and therefore is useful for kinetic studies using substrate analogues. Here, we report the expression in Escherichia coli of a hexahistidine-tagged guinea pig liver tissue transglutaminase (His(6)-tTGase) allowing rapid purification by immobilized-metal affinity chromatography. Using this procedure we have obtained the highest reported specific activity (17 U/mg) combined with a high yield (22 mg/L of culture) for recombinant TGase using a single-step purification protocol. Using two independent spectrophotometric assays, we determined that the K(m) value of the recombinant enzyme with the substrate Cbz-Gln-Gly is in the same range as values reported in the literature for the native enzyme. We have thus developed a rapid and reproducible protocol for the preparation of high quality tissue TGase.
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PMID:Expression and rapid purification of highly active hexahistidine-tagged guinea pig liver transglutaminase. 1471 14

The treatment of cystamine, a transglutaminase(TGase) inhibitor, has beneficial effects in several diseases including CAG-expansion disorders and cataract. We compared the inhibition characteristics of cystamine with those of cysteamine, a reduced form of cystamine expect-ed to be present inside cells. Cystamine is a more potent inhibitor for TGase than cysteamine with different kinetics pattern in a non-reducing condition. By contrast, under reducing conditions, the inhibitory effect of cystamine was comparable with that of cysteamine. How-ever, cystamine inhibited intracellular TGase activity more strongly than cysteamine despite of cytoplasmic reducing environment, suggest-ing that cystamine itself inhibits in situ TGase activity by forming mixed disulfides.
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PMID:Different inhibition characteristics of intracellular transglutaminase activity by cystamine and cysteamine. 1567 41

Transglutaminases (TGases), a family of enzymes that catalyze the formation of epsilon-(gamma-glutamyl)lysine isopeptide linkage, play an important physiological role in hemostasis, wound healing, assembly and remodeling of the extracellular matrix, cell signaling and apoptosis. Although many members of this class of enzymes have been known for decades, their role in various physiological and pathological processes is still a subject of substantial research and debate. Convincing evidence exists that TGases are involved in formation of cytotoxic proteinatious aggregates in Alzheimer's, Huntington's and other neurodegenerative diseases. However, it is not clear if elevated levels of TGases play a causative or protective role in several of these processes. Increased or defective TGase activity is a factor in cortical cataract formation, lamellar ichtyosis and fibrosis. TGase creates epitopes for the production of autoantibodies in celiac disease and possibly other autoimmune diseases. Another TGase, Factor XIIIa, is involved in the etiology of vascular diseases. Modulation of TGase activity through its selective inhibition may have therapeutic benefit in a wide variety of diseases. This paper will examine TGases as targets for the development of new therapeutics and review the progress in discovery of selective inhibitors of these enzymes.
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PMID:Transglutaminases as targets for pharmacological inhibition. 1577 62