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)

The objectives of this experiment were to assess effects of animal age and castration on activities of calpain I, calpain II, and calpastatin in sheep skeletal muscle. Ten newborn male lambs (2.9 kg), six weaned wethers (23.2 kg), six weaned rams (22.2 kg), six market wethers (55.4 kg), and six market rams (60.2 kg) were slaughtered and samples of biceps femoris were taken for assay of calpain I (micromolar calcium-dependent proteinase), calpain II (millimolar calcium-dependent proteinase), and calpastatin. Preweaning weight gain was similar for rams and wethers; however, postweaning ram growth exceeded (P less than .05) that of wethers. Ram biceps femoris weights at market were greater than those of wethers (P less than .05). Irrespective of age or gender, activity of calpain II was two- to threefold greater than that of calpain I. Muscle calpastatin activity was severa fold higher than calpain I and II activities. Activities of calpains and calpastatin declined (P less than .05) between birth and weaning. A portion of these losses were due to a dilution effect caused by accumulation of muscle proteins. Neonatal attenuation of calpain activities may underlie age-related attenuation of fractional rates of muscle protein degradation. Although ram muscle growth exceeded that of wethers, no differences (P greater than .05) in activities of muscle calpains or calpastatin were detected between these two groups at weaning or at market weight. Hence, castration did not influence lamb muscle growth by altering muscle calpain or calpastatin activities.
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PMID:Effects of age and castration on activities of calpains and calpastatin in sheep skeletal muscle. 171 52

Our objectives were to characterize events underlying changes in skeletal muscle calpain and calpastatin activities, using maturation as a model. Muscle samples were taken from rabbits of four ages (newborn and 1, 2, and 5 mo old). Concentrations of RNA and protein and activities of calpains I and II and calpastatin were determined. Steady-state concentrations of mRNAs encoding calpain I, calpain II, calpastatin, alpha- and beta-tubulin, and beta-actin were determined using Northern blot analysis. Calpain and calpastatin activities declined markedly between birth and 1 mo of age and remained unchanged thereafter. Several factors accounted for the neonatal losses of calpains and calpastatin. First, muscle protein concentration increased between birth and 1 mo of age and diluted calpain and calpastatin specific activities. Second, there was a marked reduction of muscle RNA concentration between birth and 1 mo of age, which indicates that protein synthetic capacity declined with age. Finally, calpastatin mRNA concentration declined between birth and 1 mo of age and further contributed to developmental losses of calpastatin activity. Calpain I mRNA concentration was unaffected by age, and although calpain II mRNA concentration declined with age, losses were not detected between birth and 1 mo; hence age-related changes in calpain I and II activities are not mediated at the mRNA level. The age-related reductions in calpain II and calpastatin mRNA concentrations resembled age-related changes in alpha- and beta-tubulin and beta-actin mRNA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determination of skeletal muscle calpain and calpastatin activities during maturation. 176 27

Two forms of calpastatin, differing in their specificity for the homologous calpain isozymes I and II, have been separated from rat skeletal muscle extracts and purified to homogeneity. Calpastatin I, the first form to elute in chromatography on DE32, is more effective against calpain I, while calpastatin II is more effective as an inhibitor of calpain II. Based on their molecular mass (approximately 105 kDa) both calpastatin forms belong to the high molecular mass class found in muscles of other animal species (Murachi, T., 1989, Biochem. Int. 18, 263-294). For calpain I, which is active with low (mu-M) concentrations of Ca2+, maximum inhibition with either calpastatin form was observed over a wide range of Ca2+ concentrations. With calpain II, which requires high (mM) concentrations of Ca2+ for activity, maximum inhibition required Ca2+ concentrations above 1 mM. Both calpastatin forms were found to be highly sensitive to degradation by calpain II, but almost completely resistant to degradation by calpain I. Degradation of calpastatin by calpain II is competitively inhibited by the addition of a calpain substrate. Isovaleryl carnitine (IVC), an intermediate product of L-leucine catabolism, previously demonstrated to be a potent and specific activator of rat skeletal muscle calpain II (Pontremoli, S., Melloni, E., Viotti, P. L., Michetti, M., Di Lisa, F., and Siliprandi, N., 1990. Biochem. Biophys. Res. Commun. 167, 373-380) greatly enhances the rate of degradation of calpastatins by calpain II. IVC, which decreases the Ca2+ requirement for maximal calpain II activity, also decreases the concentration of Ca2+ required for digestion of the inhibitor. For calpain II, regulation by either calpastatins may occur only in the presence of high [Ca2+].
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PMID:Identification of two calpastatin forms in rat skeletal muscle and their susceptibility to digestion by homologous calpains. 189 54

The muscle enzyme calpain II, in contrast to muscle calpain I, was markedly inhibited by millimolar concentrations of the polyamines spermine and spermidine. These compounds and the calpain inhibitor calpastatin had synergistic inhibitory effects on calpain II. These results suggest that the polyamines may have possible regulatory effects on the in vivo activity of calpain II enzymes.
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PMID:Inhibitory effects of spermine and spermidine on muscle calpain II. 231 18

An additional component of the regulatory system of rat skeletal muscle calpain has been identified. It exerts a potent activating effect on calpain activity and is a heat stable small molecular weight protein. Of the two calpain isozymes present in muscle, the activator is specific for calpain II, being uneffective with calpain I. It promotes activation of the proteinase by reducing 50 fold, from 1 mM to of 20 microM, the requirement of Ca2+ for maximum catalytic activity of the proteinase. However in the presence of the activator calpain II expresses a consistent fraction of the maximum activity even at significantly lower concentrations of Ca2+ (below 5 microM Ca2+). The activator effect follows kinetics that are consistent with the presence of specific binding sites on the calpain molecules. The activator not only removes in a dose dependent fashion the inhibition of calpain by calpastatin, but also prevents inhibition of the proteinase upon the addition of calpastatin. Competition experiments revealed that the proteinase contains distinct sites for the activator and the inhibitor, and that both ligands can bind to calpain with the formation of an almost fully active ternary complex.
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PMID:Identification of an endogenous activator of calpain in rat skeletal muscle. 240 49

Observations described here provide the first demonstration that calpain (Ca2+-dependent cysteine protease) can degrade proteins of skeletal muscle plasma membranes. Frog muscle plasma membrane vesicles were incubated with calpain preparations and alterations of protein composition were revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Calpain II (activated by millimolar concentrations of Ca2+) was isolated from frog skeletal muscle, but the activity of calpain I (activated by micromolar concentrations of Ca2+) was lost during attempts at fractionation. Calpain I obtained from skeletal muscle and erythrocytes of rats was tested instead, and exerted effects similar to those of frog muscle calpain on the membrane proteins. All of the calpain preparations caused striking losses of a major membrane protein of molecular mass of approximately 97 kDa, designated band c, and diminution of a thinner band of approximately 200 kDa. There were concomitant increases in 83- and 77-kDa polypeptides. These effects were absolutely dependent on the presence of free Ca2+, and were completely blocked by calpastatin, a specific inhibitor of calpain action. Frog muscle calpain differed only in being relatively more active at 0 degree C than were the calpains from rat tissues. Experimental observations suggest that calpain acts at the cytoplasmic surface of the plasma membrane.
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PMID:Degradation of skeletal muscle plasma membrane proteins by calpain. 255 77

1. Carnosine, anserine and L-1-methyl-histidine activated muscle calpain II assayed at 2.5 mM Ca2+. 2. At 5 microM Ca2+, none of these compounds activated calpain II sufficiently to bring its activity up to the level measured at 2.5 mM Ca2+. 3. Carnosine increased, whereas both anserine and L-1-methyl-histidine decreased the inhibitory effect of calpastatin on calpain II. 4. These results suggest that although the compounds are not potent activators of calpain II, the ratio of the dipeptides in muscle may have an effect on calpain II-calpastatin interaction.
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PMID:Effects of L-1-methyl-histidine and the muscle dipeptides carnosine and anserine on the activities of muscle calpains. 255 85

Calpain (Ca2+-dependent cysteine proteinase) was purified to apparent homogeneity from carp muscle by the method of DEAE-cellulose, hydroxylapatite and Ultrogel AcA 34 column chromatographies. The purified enzyme is classified as calpain II (high-Ca2+-requiring form of calpain) from the effects of Ca2+ concentration, pH and the antibiotics on the activity. Carp muscle calpain II was inhibited by rat liver calpastatin, the specific inhibitor for calpain. It is probable that the calpain-calpastatin system may play a biologically fundamental and common role in various cells, since the inhibitory effect of calpastatin on calpain from different tissues of different species is well conserved.
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PMID:Purification and properties of carp (Cyprinus carpio) muscle calpain II (high-Ca2+-requiring form of calpain). 299 71

Structural changes in the Z disk were sensitively detected by measuring fragmentation indexes of myofibrils. The Ca2+-induced weakening of Z disks and the Z-disk removal by muscle calpain could be clearly distinguished by using muscle calpastatin, an endogenous inhibitor of muscle calpain. The Ca2+-induced weakening of Z disks occurred without concomitant release of alpha-actinin and had maxima at 10(-4) M Ca2+ and 45 degrees C and a minimum at pH 6.5, while the Z-disk removal by calpain had similar optima to the caseinolytic activity of calpain, at 10(-3) M Ca2+, 20 degrees C and pH 7.0. The Ca2+-induced weakening of Z disks is therefore not due to the proteolytic action of calpain. In postmortem muscle, moreover, the Ca2+-induced weakening of Z disks was inferred to be predominate over calpain proteolysis, and therefore to be the major factor in the characteristic weakening of Z disks.
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PMID:Calcium-induced weakening of skeletal muscle Z-disks. 629 Apr 62

The objectives were to investigate the mechanisms by which glucocorticoids control proteolysis in muscle cells and the relationship between the calpain:calpastatin system and proteolysis in muscle. Female rabbits were treated with 1 mg dexamethasone (Dex)/kg body weight per day for 0, 1, 2 or 4 days after which animals were killed and muscle samples taken for analyses. Dex reduced urinary N tau-methylhistidine (NMH) 48% (day 4 versus day 1 of Dex treatment) and muscle NMH concentrations by 49% (day 1) to 40% (day 2) respectively, suggesting that protein degradation was reduced. To investigate whether the changes in apparent proteolysis were related to calpains, we examined the effects of Dex on muscle calpain and calpastatin activities. These were unaffected by Dex. This implies that Dex-dependent changes in degradation are not mediated by changes in muscle calpain or calpastatin activities. We studied the effects of Dex on calpain and calpastatin gene expression as a means of clarifying the relationships between proteinase gene expression and proteinase activities. mu-Calpain mRNA concentration was unaffected by Dex but m-calpain mRNA and calpastatin mRNA concentrations were reduced by 42-55% and 40% respectively. Dex had a similar effect on beta-actin mRNA. Although calpain and calpastatin genes behaved as house-keeping genes, changes in their expression mimicked apparent changes in proteolysis. The observation that calpain and calpastatin activities were unchanged indicates that additional regulation of the calpain:calpastatin system exists at other sites in muscle cells. To determine whether Dex-dependent changes in proteolysis were mediated indirectly, we assayed the effects of Dex on plasma thyroid hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dexamethasone on muscle protein homeostasis and on calpain and calpastatin activities and gene expression in rabbits. 751 33


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