Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.54 (calpain 3)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steers of known percentage Brahman (B) and Angus (A) breeding (100% A, n = 6; F1 B x A, n = 6; and 100% B, n = 6) were used to determine the effect of calcium chloride injection on the calpain proteinase system and meat tenderness. The steers were slaughtered in six replications (at either 9 or 14 mm of backfat, determined ultrasonically), with each breed type represented. Calpains and calpastatin activities were measured on fresh, prerigor longissimus muscle samples. Carcass data were collected after a 24-h chill, and the short loin (IMPS #180), top sirloin (IMPS #184), and top round (IMPS #168) were removed from both sides of each carcass. The cuts from the right side were then injected at 5% (wt/wt) with CaCl2 solution (2.2%). Longissimus muscle calpain and calpastatin activities were also measured at 48 h postmortem from the injected and control sides of each carcass. Warner-Bratzler shear force was measured on steaks from the three subprimals aged 1, 2, 5, 15, or 31 d. Marbling scores and USDA quality grades were higher (P<.05) in A than in F1 B x A and B carcasses. Calpastatin activity was higher (P<.05) in muscle from B than in muscle from A and F1 B x A steers, and postmortem storage (O vs 48 h) and CaCl2 injection reduced (P<.05) the activity of the calpains and calpastatin. Strip loin and top sirloin steaks from A and F1 B x A steers were more tender (P<.05) than steaks from B steers; however, top round steak tenderness did not differ (P>.05) across breed type. Calcium injection improved strip loin and top sirloin steak tenderness, but it did not affect top round steak tenderness. Collectively, these data show that CaC12 injection can be used to improve meat tenderness, with similar responses shown in cattle containing 0, 50, and 100% B inheritance. However, even with CaCl2 injection, B steaks are less tender than their A and F1 B x A counterparts.
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PMID:Calcium-activated tenderization of strip loin, top sirloin, and top round steaks in diverse genotypes of cattle. 1064 69

This lecture traces recent advances in knowledge of the muscular dystrophies, as well as their increasing complexity. They are described through the eyes of the author from his first exposure to and complete ignorance of the disease in the late 1950s, through the advent of modern techniques, to the molecular genetic revolution, with the recognition of individual genes and proteins for disorders within the muscular dystrophy umbrella. There initially seemed to be a logical sequence of linked membrane proteins from dystrophin in Duchenne and Becker dystrophy, through the dystrophin-associated glycoproteins (sarcoglycans) in some of the limb girdle muscular dystrophies (LGMD), to the extracellular matrix protein merosin (alpha-2 laminin) in congenital muscular dystrophy (CMD). The first spoke in the wheel came with the discovery of a calcium activated protease enzyme, calpain 3, in one form of LGMD, and subsequently another novel non-membrane protein, dysferlin, in another. There are currently at least eight distinct genetic forms of LGMD alone, and another eight separate genetic entities in the CMD group. This has highlighted our ignorance of the pathogenesis of the muscular dystrophies in relation to a diverse array of protein deficiencies. To compound things further, the X-linked and dominant forms of Emery-Dreifuss muscular dystrophy have recently been linked to emerin and lamin A/C, respectively, two proteins of the nuclear membrane, opening up yet another new ballpark of discovery.
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PMID:What is muscular dystrophy? Forty years of progressive ignorance. 1107 61

The effects of dantrolene on serum TNFalpha and corticosterone levels and on muscle calcium, calpain gene expression, and protein breakdown were studied in rats with abdominal sepsis induced by cecal ligation and puncture. Treatment of rats with 10 mg/kg of dantrolene 2 h before and 8 h after induction of sepsis reduced serum TNFalpha and corticosterone, muscle calcium levels, mRNA levels for m- and mu-calpain, and the muscle specific calpain p94, as well as total and myofibrillar protein breakdown rates, determined as release of tyrosine and 3-methylhistidine, respectively, from incubated extensor digitorum longus muscles. The results support the concept that increased calcium concentrations may be an important mechanism of sepsis-induced muscle protein breakdown. The data also indicate that other mechanisms, in addition to reduced muscle calcium concentrations such as decreased levels of TNFalpha and glucocorticoids, may contribute to the anti-catabolic effects of dantrolene during sepsis. The observations are important from a clinical standpoint because they suggest that the catabolic response in skeletal muscle during sepsis may be prevented by treatment with a calcium antagonist.
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PMID:Dantrolene reduces serum TNFalpha and corticosterone levels and muscle calcium, calpain gene expression, and protein breakdown in septic rats. 1123 3

The proteins nCL-2 and nCL-2' are members of the Ca2+-dependent cysteine protease (calpain) superfamily, with stomach-specific expression. Like other typical calpains, nCL-2 has three distinct domains, a protease, a C2-like, and a 5EF-hand Ca2+-binding domain, as well as the N-terminal propeptide region. On the other hand, nCL-2' lacks the C2-like and 5EF-hand domains but is otherwise identical to nCL-2, except for the three C-terminal residues. To examine the stomach-specific and presumed alternative expression mechanisms of nCL-2 and nCL-2', we have cloned and characterized the mouse gene for nCL-2 and nCL-2'. The mouse nCL-2 gene contains at least 23 exons, spanning more than 50 kb, and possesses an exon specific for nCL-2' in the middle. Therefore, nCL-2 and nCL-2' are generated by alternative splicing of the same gene, Capn8. Capn8 shows the highly conserved gene organization of the other typical calpain large subunit genes, CAPN1, CAPN2, CAPN3, CAPN9, CAPN11, and Capn12, except for the unique exon between exon 9 and exon 10 of Capn8, which encodes the 3' half of the nCL-2' transcript. No such exon in the corresponding regions was found in CAPN1, CAPN2, CAPN3, CAPN9, or CAPN11. Gene and cDNA structures of a presumed human orthologue of mouse nCL-2, CAPN8, were determined, revealing that it overlaps human CAPN2, the gene for the m-calpain large subunit, in head-to-head orientation at 1q32-41. These features of Capn8 and CAPN8 illustrate a process of calpain gene evolution, i.e., the protease, C2-like, and 5EF-hand domains presumably functioned as independent genes, and the calpain superfamily has evolved by ordered fusions of these ancestral gene units, with subsequent amplifications.
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PMID:Both the conserved and the unique gene structure of stomach-specific calpains reveal processes of calpain gene evolution. 1152 6

Eye tissues contain splice variants of muscle-preferred p94 (calpain 3), such as lens-specific Lp82 and Lp85, retina-specific Rt88, and cornea-specific Cn94. The purpose of the present experiment was to analyze the activation and regulation of the best characterized p94 splice variant, Lp82. Recombinant rat Lp82 (rLp82) was expressed using the baculovirus system, purified with Ni-NTA affinity and DEAE-ion exchange chromatographies, and characterized by SDS-PAGE, casein zymography, and immunoblotting. After incubation with calcium, rLp82 autolyzed into two major fragments at approximately 60 and 22 kDa. Sequencing of the autolytic fragments showed loss of three amino acids from the N terminus and cleavage near the IS2 region. Also, Lp82 and calpain 2 were found to hydrolyze each other. Calpastatin inhibited calpain 2 activity, but not Lp82. Homology modeling suggested that the lack of inhibition of Lp82 by calpastatin was due to molecular clashes at the unique AX1 region of Lp82. Lp82 also hydrolyzed calpastatin. These results suggested that Lp82 might regulate other calpain activities and cause hydrolysis of substrates such as crystallins during lens cataract formation.
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PMID:Characterization and regulation of lens-specific calpain Lp82. 1190

Many studies have demonstrated that the calcium-dependent proteolytic system (calpains and calpastatin) is involved in myoblast differentiation. It is also known that myogenic differentiation can be studied in vitro. In the present experiments, using a mouse muscle cell line (C2C12) we have analyzed both the sequences of appearance and the expression profiles of calpains 1, 2, 3 and calpastatin during the course of myoblast differentiation. Our results mainly show that the expression of ubiquitous calpains (calpain 1 and 2) and muscle-specific calpain (calpain 3) at the mRNAs level as well as at the protein level do not change significantly all along this biological process. In the same time, the specific inhibitor of ubiquitous calpains, calpastatin, presents a stable expression at mRNAs level as well as protein level, all along myoblast to myotube transition. A comparison with other myogenic cells is presented.
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PMID:Characterization of the calcium-dependent proteolytic system in a mouse muscle cell line. 1195 56

p94 belongs to the calpain family of enzymes, also called calcium-activated neutral proteases and is mainly expressed in the skeletal muscle. Mutations affecting the gene coding for p94 are responsible for a myopathy syndrome called Limb Girdle Muscular Dystrophy type 2A (LGMD2A). Although the activity of p94 seems necessary for muscle function, the biological role of the enzyme is still unknown. The goal of this study was to develop a muscle cell line in which the expression level of p94 can be regulated, by an inducible way. In this study, a biological system was developed which allowed mimicking, in vitro, of part of the events occurring in patients (i.e. a decrease of p94 activity). The first results indicate that the decrease in p94 activity results in a significant increase of myogenin level, a high specific transcription factor involved in myoblast fusion. This muscle specific inducible system is an interesting biological tool to assess specifically p94 function(s) in cultured muscle cells. According to the present results, p94 seems at least to be involved in a myogenesis regulation pathway via its action on certain proteins belonging to the myogenic regulator factor family.
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PMID:Development of an inducible system to assess p94 (CAPN3) function in cultured muscle cells. 1204 55

Reduced sarcolemmal integrity in dystrophin-deficient muscles of mdx mice and Duchenne muscular dystrophy (DMD) patients has been reported to result in altered calcium homeostasis. Previous studies have shown a correlative relationship between calcium-dependent protease (calpain) activity in dystrophic muscle and muscle necrosis, but have not tested whether calpain activation precedes cell death or is a consequence of it. To test a causal relationship between calpain activation and muscle cell death in dystrophin deficiency, mdx mice were generated that overexpress a calpastatin transgene in muscle. Calpastatin (CS) is a specific, endogenous inhibitor of m- and micro -calpains that does not inhibit calpain 3 (p94). CS overexpression on a C57/BL 10 background produced no phenotype. Transgenic (Tg) mice crossed with mdx mice were tested for pathological indicators of necrosis, regeneration and membrane damage. Two lines of mice were examined, with different levels of CS overexpression. Both lines of Tg/mdx mice showed reductions in muscle necrosis at 4 weeks of age. These mice had fewer as well as smaller lesions. In addition, one line of mice had significantly less regeneration, indicating a reduction in previous necrosis. The extent of improvement correlated with the level of CS protein expression. Membrane damage, as assessed by procion orange and creatine kinase assays, was unchanged, supporting the idea that calpains act downstream of the primary muscle defect. These data suggest that calpains play an active role in necrotic processes in dystrophic muscle and that inhibition of calpains might provide a good therapeutic option for treatment of DMD.
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PMID:Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology. 1235 90

The calpain system is a family of calcium activated proteases that degrade myofibrillar protein. Male broiler chickens (Ross) were provided a standard starter diet top-dressed with Oasis((R)) nutritional supplement (fed; Novus International, St. Louis, MO, USA), or they were not provided any feed (starved) for the first 3 days posthatch. Subsequently, the standard starter diet was provided to all chickens between 3 and 7 days posthatch. RNA was extracted from the Pectoralis thoracicus, and skeletal muscle-specific n-calpain-1 (p94) calpain, mu-calpain, and m-calpain expression was evaluated using quantitative Northern analysis. Early posthatch starvation did not (P>0.05) affect calpain mRNA levels on each day examined. Similarly, there were no (P>0.05) changes in mu-calpain or m-calpain mRNA levels between 0 and 7 days posthatch in fed birds. However, p94 calpain mRNA levels were significantly (P<0.05) lower at 7 days posthatch compared to 0 or 2 days posthatch. Therefore, in the early posthatch chicken, it appears that the calpain system may not be affected by the presence of oral nutrition, and that there is an age-related downregulation of p94 calpain mRNA expression.
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PMID:The effect of early posthatch starvation on calpain mRNA levels. 1238 84

We have performed expression profiling to define the molecular changes in dysferlinopathy using a novel dedicated microarray platform made with 3'-end skeletal muscle cDNAs. Eight dysferlinopathy patients, defined by western blot, immunohistochemistry and mutation analysis, were investigated with this technology. In a first experiment RNAs from different limb-girdle muscular dystrophy type 2B patients were pooled and compared with normal muscle RNA to characterize the general transcription pattern of this muscular disorder. Then the expression profiles of patients with different clinical traits were independently obtained and hierarchical clustering was applied to discover patient-specific gene variations. MHC class I genes and genes involved in protein biosynthesis were up-regulated in relation to muscle histopathological features. Conversely, the expression of genes codifying the sarcomeric proteins titin, nebulin and telethonin was down-regulated. Neither calpain-3 nor caveolin, a sarcolemmal protein interacting with dysferlin, was consistently reduced. There was a major up-regulation of proteins interacting with calcium, namely S100 calcium-binding proteins and sarcolipin, a sarcoplasmic calcium regulator.
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PMID:Gene expression profiling in dysferlinopathies using a dedicated muscle microarray. 1247 Oct 55


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