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)

Calpains are calcium-dependent intracellular nonlysosomal proteases that are believed to hydrolyze specific substrates important in calcium-regulated signaling pathways. Recently, an atypical member of the calpain family, calpain 10, was described, and genetic variation in this gene was associated with an increased risk of type II diabetes mellitus in humans. In the present report, a polyclonal antibody directed against rat calpain 10 was developed. This antibody was used to monitor the expression of calpain 10 protein in tissues from rats, mice, and humans. Calpain 10 protein was found to be present in all tissues examined by Western blotting including the lens, retina, brain, heart, and skeletal muscle. Although some calpain 10 was detectable in the water-soluble protein fraction of these tissues, it was preferentially found in the water-insoluble fraction. In the lens, immunohistochemistry revealed that calpain 10 was predominately located in the cytoplasm of epithelial and newly differentiating lens fibers at the transition zone. However, calpain 10 was found to be associated with the plasma membrane of differentiated lens fiber cells and the sarcolemma of skeletal muscle. In the lens epithelium-derived cell line, alphaTN4-1, the calpain 10 protein was found in a punctate distribution in the cell nucleus as well as the cytoplasm. After the elevation of intracellular calcium levels with ionomycin, calpain 10 protein levels in the nucleus of alphaTN4-1 cells increased markedly, whereas those in the cytoplasm decreased. In the lens, the elevation of intracellular calcium levels after selenite administration resulted in increased levels of calpain 10 RNA within 1 day and a loss of calpain 10 protein from the lens nucleus coincident with the onset of selenite cataract. In conclusion, calpain 10 seems to be a ubiquitous calpain, the expression level and subcellular distribution of which are dynamically influenced by calcium.
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PMID:Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization. 1137 82

To determine the involvement of calpains in human cataractogenesis, studies in aged animal models are needed. Aged, male WBN/Kob rats spontaneously develop cataract along with severe, persistent diabetes with hyperglycemia and nephropathy. The purpose of present experiments was to provide a biochemical mechanism for the involvement of ubiquitous calpains in cataractogenesis in WBN/Kob rats. Serum and urinary glucose were measured to confirm diabetes, and cataracts were observed by slit lamp biomicroscopy. Calcium determinations were performed on lens samples from several ages of WBN/Kob and Wistar rats. Casein zymography, immunoblot analysis for alpha-spectrin, calpain 2, and calpain 10 were performed to detect activation of calpain in lens samples. Serum glucose levels increased and cortical cataract developed in male WBN/Kob rats within 1 year, indicating diabetic cataract. Cataract was accompanied by several presumptive biochemical indicators of calpain activation, including increased calcium, proteolysis of alpha-spectrin, and decreased caseinolytic activity for calpains suggesting calpain activation followed by autolytic degradation. Activation of ubiquitous calpains may contribute to biochemical mechanism of cataractogenesis in spontaneously diabetic WBN/Kob rats. The WBN/Kob model may be useful for elucidating the roles of calpain 2 and calpain 10 in human cataractogenesis.
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PMID:Contribution of ubiquitous calpains to cataractogenesis in the spontaneous diabetic WBN/Kob rat. 1245 73

Calcium activated proteases (calpains) have been implicated in the processing of lens crystallins during lens maturation and cataract formation. Ubiquitous type calpain 2 and calpain 10 and lens specific Lp82 and Lp85 protein distribution were determined using immunohistochemistry and immunoblotting in embryonic and post-natal mouse eyes. Calpain 2 was first expressed late in embryonic development and localized to the lens epithelium and transition zone. Lp82 was expressed at E9.5 in the lens placode, head ectoderm, and throughout the fiber cells during embryonic lens maturation. Lp82 co-localized at sites of crystallin modification in the juvenile lens. In the adult lens, Lp82 protein was maintained in cortical fibers but could not be detected in the lens nucleus. Lp85, the slightly larger splice variant of Lp82, was first observed at E9.5 and throughout early embryonic lens development. Abundant localization of this enzyme was observed in the cell nuclei of lens epithelium, elongating fibers, and undifferentiated mesoderm. Robust peri-nuclear localization of calpain 10 was observed in the head ectoderm, lens placode, and optic vesicle during early eye induction. Further, calpain 10 protein was maintained in the lens epithelium of pre- and post-natal lens. These data support the hypothesis that Lp82 in rodent lens has an important role in crystallin proteolysis during normal lens maturation. In contrast, calpain 2, Lp85, and calpain 10 may have roles in cell signaling pathways.
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PMID:Protein expression patterns for ubiquitous and tissue specific calpains in the developing mouse lens. 1263 8

Calpain, a Ca(2+)-requiring cytoplasmic cysteine protease, plays indispensable roles in various cellular functions such as signal transduction, cell growth and differentiation, apoptosis, necrosis, and so on. Although most of the detailed physiological functions of calpains have not yet been elucidated, the importance of calpain is obvious from the increasing numbers of papers describing relationships between human disease states (such as Alzheimer's disease, cataract, and muscular dystrophies) and malfunction of calpain. One of the recent remarkable topics of calpain is that a single nucleotide polymorphism of CAPN10, the gene for calpain 10, is related to type 2 diabetes. However, physiological functions of calpain 10 and its relation to diabetes are still unclear. Among 14 human calpain genes, mutations in CAPN3, the gene for p94/calpain 3a and Lp82/calpain 3b, are the only example that genetically connects the calpain gene and human disease, in this case, limb-girdle muscular dystrophy type 2A (LGMD2A). p94 has unique characteristics such as apparent Ca(2+)-independent activation and very rapid autolytic activity, which are dependent on p94-specific regions, NS, IS1, and IS2. Based on the 3D structures of micro - and m-calpain, molecular functions of p94 in relation to LGMD2A are discussed, with the hope of providing us with some clues to understand calpain functions and its relationships to human diseases.
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PMID:[Calpain and pathology in view of structure-function relationships]. 1284 69

Premature visual impairment due to lens opacification is a debilitating characteristic of untreated diabetes. Lens opacification is primarily due to the insolubilization of crystallins, proteins essential for lens optical properties, and recent studies have suggested that a major cause of this insolubilization may be the unregulated proteolysis of crystallins by calpains. These are intracellular cysteine proteases whose activation requires the presence of calcium (Ca2+) and elevated levels of lens Ca2+ is a condition associated with both diabetic cataractogenesis and other forms of the disorder. A number of calpains have been identified in the lens, including calpain 2, calpain 10 and two isozymes of calpain 3: Lp82 and Lp85. The use of animal hereditary cataract models have suggested that calpain 2 and/or Lp82 may be the major calpains involved in murine cataractogenesis with contributions from calpain 10 and Lp85. However, calpain 2 appears to be the major calpain involved in murine diabetic cataractogenesis and the strongest candidate of the calpains for a role in human types of cataractogenesis. Here, we present an overview of recent evidence on which these observations are based with an emphasis on the ability of calpains to proteolyse lens crystallins and calpain structural features, which appear to be involved in the Ca2+-mediated activation of these enzymes.
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PMID:Role of calpains in diabetes mellitus-induced cataractogenesis: a mini review. 1536 98