Differential Regulation of μ-Calpain and m-Calpain in Rat Hearts Perfused with Ca2+ and cAMP

Salamino, Franca; Detullio, R.; Mengotti, P.; Melloni, Edon; Pontremoli, S.

doi:10.1006/bbrc.1994.2057

Cited by 8 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both PKA and PKC, which are activated downstream of the CT receptor (29,34,36,37), phosphorylate the two calpains (42,43,83) and the endogenous calpain inhibitor calpastatin (84 -86), whose specificity and inhibitory efficiency are modulated by both PKA and PKC (40,41). In addition, calpastatin is activated by lower, more physiological cytosolic Ca 2ϩ concentrations (87)(88)(89), suggesting that the increase in [Ca 2ϩ ] i induced by CT (38) might contribute to calpain inhibition in osteoclasts.…”

Section: Discussionmentioning

confidence: 99%

Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin

Marzia

Chiusaroli

Neff

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Osteoclast motility is thought to depend on rapid podosome assembly and disassembly. Both -calpain and m-calpain, which promote the formation and disassembly of focal adhesions, were observed in the podosome belt of osteoclasts. Calpain inhibitors disrupted the podosome belt, blocked the constitutive cleavage of the calpain substrates filamin A, talin, and Pyk2, which are enriched in the podosome belt, induced osteoclast retraction, and reduced osteoclast motility and bone resorption. The motility and resorbing activity of -calpain ؊/؊ osteoclast-like cells were also reduced, indicating that -calpain is required for normal osteoclast activity. Histomorphometric analysis of tibias from -calpain ؊/؊ mice revealed increased osteoclast numbers and decreased trabecular bone volume that was apparent at 10 weeks but not at 5 weeks of age. In vitro studies suggested that the increased osteoclast number in the -calpain ؊/؊ bones resulted from increased osteoclast survival, not increased osteoclast formation. Calcitonin disrupted the podosome ring, induced osteoclast retraction, and reduced osteoclast motility and bone resorption in a manner similar to the effects of calpain inhibitors and had no further effect on these parameters when added to osteoclasts pretreated with calpain inhibitors. Calcitonin inhibited the constitutive cleavage of a fluorogenic calpain substrate and transiently blocked the constitutive cleavage of filamin A, talin, and Pyk2 by a protein kinase C-dependent mechanism, demonstrating that calcitonin induces the inhibition of calpain in osteoclasts. These results indicate that calpain activity is required for normal osteoclast activity and suggest that calcitonin inhibits osteoclast bone resorbing activity in part by down-regulating calpain activity.Osteoclasts are large multinucleated cells of the monocyte-macrophage lineage that play a critical role in skeletal development and repair and in calcium homeostasis by resorbing mineralized cartilage and bone. They display a high degree of motility, which is required for normal bone resorbing activity. As in other highly motile cells, the integrinbased attachment complexes of osteoclasts are podosomes, which are structurally and functionally distinct from focal adhesions (1-6). Although many of the same proteins are present in both podosomes and focal adhesions, podosomes are notably more dynamic, undergoing assembly and disassembly within minutes (5-7). The rapid and cyclic podosome assembly and disassembly and their dynamic interaction with elements of the actin cytoskeleton are thought to be critical for the high motility of osteoclasts (7).Recently, calpains have been found to play crucial roles in the regulation of motility in cells such as fibroblasts that form focal adhesions (8). Calpains are a family of cytosolic cysteine proteases, many of which are Ca 2ϩ -dependent, that catalyze the limited cleavage of specific proteins during regulatory signaling (9, 10). The most studied members of the calpain family are the ubiquitously expressed -calpain ...

show abstract

Section: Discussionmentioning

confidence: 99%

Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin

Marzia

Chiusaroli

Neff

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…This essentially means that the period for which calcium remains in the cytosol is higher for canB2 mutants thereby leading to uncontrolled contraction and untimely activation of several calcium-activated proteases like calpains leading to cell death. Possible substrates of calpains are the membrane cytoskeleton, the Ca 2+ -ATPase of the plasma membrane, and ion channel proteins (Salamino et al, 1994). The action of calpain on plasma membrane Ca 2+ channels can lead to increase openings of these channels (Turner et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Knock down of Calcineurin-B2, a calcium binding regulatory subunit of Calcineurin, gives rise to hypercontraction myopathy in indirect flight muscles ofDrosophilathrough dysregulation of calcium homeostasis

Jhonsa

Nongthomba

2017

Preprint

View full text Add to dashboard Cite

Abstract/SummaryMuscle is a calcium responsive tissue and requires calcium for initiation of muscle contraction. Calcium concentration in muscle is tightly regulated by calcium binding proteins. Calcineurin-B2 (canB2), a calcium binding, regulatory subunit of calcineurin, is the isoform maximally expressed in the indirect flight muscles (IFMs) of Drosophila. The developmental and functional roles of CanB2 particularly in the maintenance of calcium homeostasis are not understood. In this study, we show that the loss of canB2 causes hypercontraction of IFMs. Genetic interaction studies with hypercontraction mutants suggest a synergistic interaction between Calcineurin-B2 and structural protein Troponin-T. Similarly, interaction studies with dSERCA mutant reveal that Calcineurin-B2 is important for regulating calcium homeostasis in muscles. In vivo calcium imaging showed that Calcineurin-B2 deficiency leads to arrhythmicity in the calcium oscillations. We show that Calcineurin-B2 knockdown causes deregulation of calcium homeostasis, which results in unregulated acto-myosin interaction. However, overexpression of Calcineurin-A, which inhibits calcium oscillations, had no effect on myofibrillogenesis suggesting that calcium activation is dispensable for myofibrillar assembly. Our findings contribute to the understanding of muscle physiology in normal as well as pathophysiological conditions.

show abstract

“…On the contrary, the lack of effect observed on µ-calpain activity was unexpected. This agerelated discrepancy between calpastatin behaviour on the two ubiquitous enzymes could be explained by the existence of a differential regulation by distinct phosphorylated forms of the inhibitor like postulated in the past (Salamino et al, 1994). Moreover it is important to highlight that in our study, we tested calpastatin activity on each purified enzyme (µ-and mcalpain), while most of the reports have been done using one single calpain isoform (Averna et al, 2007;Shwarz-Benmeir, 1994).…”

Section: Accepted Manuscriptmentioning

confidence: 90%

Involvement of the calcium-dependent proteolytic system in skeletal muscle aging

Dargelos

Brulé

Combaret

et al. 2007

Experimental Gerontology

View full text Add to dashboard Cite

Aging is associated with a progressive and involuntary loss of muscle mass also known as sarcopenia. This condition represents a major public health concern with high socio-economics implications. Although sarcopenia is well documented, the aetiology of this condition still remains poorly understood. Calpains are ubiquitous proteases regulated in part by a specific inhibitor, calpastatin. They are well known to have major implications in muscle growth and differentiation. The aim of the present study was to determine if this proteolytic system could be involved in the phenotype associated with sarcopenia. Calpains and calpastatin levels, subcellular distributions and activities were compared between muscles from 3 and 24 months old rats. Altogether, the results we obtained showed an overall increase in calpain activities associated with muscle aging. These findings suggest that the calcium-dependent proteolytic system is indeed involved in sarcopenia.

show abstract

Differential Regulation of μ-Calpain and m-Calpain in Rat Hearts Perfused with Ca2+ and cAMP

Cited by 8 publications

References 0 publications

Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin

Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin

Knock down of Calcineurin-B2, a calcium binding regulatory subunit of Calcineurin, gives rise to hypercontraction myopathy in indirect flight muscles ofDrosophilathrough dysregulation of calcium homeostasis

Involvement of the calcium-dependent proteolytic system in skeletal muscle aging

Contact Info

Product

Resources

About