Calpains, particularly conventional dimeric calpains, have claimed to be involved in the cell degeneration processes that characterize numerous disease conditions linked to dysfunctions of cellular Ca 2+ homeostasis. The evidence supporting their involvement has traditionally been indirect and circumstantial, but recent work has added more solid evidence supporting the role of ubiquitous dimeric calpains in the process of neurodegeneration. The only disease condition in which a calpain defect has been conclusively involved concerns an atypical monomeric calpain: the muscle specific calpain-3, also known as p94. Inactivating defects in its gene cause a muscular dystrophy termed LGMD-2A. The molecular mechanism by which the absence of the proteolytic activity of calpain-3 causes the dystrophic process is unknown. Another atypical calpain, which has been characterized recently as a Ca 2+ - dependent protease, calpain 10, appears to be involved in the etiology of type 2 diabetes. The involvement has been inferred essentially from genetic evidence. Also in the case of type 2 diabetes the molecular mechanisms that could link the disease to calpain 10 are unknown
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alvarez, A., Toro, R., Caceres, A., Maccioni, R.B., 1999, Inhibition of tau phosphorylating protein kinase cdk5 prevents β amyloid-induced neuronal death, FEBS Lett., 459, 421–426
Anderson, L.V.B., Harrison, L.V.B., Pogue, R., Vafiadaki, E., Pollitt, C., Davison, K., Moss, J.A., Keers, S., Pyle, A., and Shaw, P.J., et al., 2000, Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies), Neuromuscul. Dis., 10, 553–559
Arrington, D., Van Vleet, T., Schnellmann, R., 2006, Calpain 10: A Mitochondrial Calpain and its Role in Calcium-induced Mitochondrial Dysfunction, Am. J. Physiol.Cell. Physiol., Baghdiguian, S., Martin, M., Richard, I., Pons, F., Astier, C., Bourg, N., Hay, R.T., Chemaly, R., Halaby, G., Loiselet, J., Anderson, L.V., Lopez de Munain, A., Fardeau, M., Mangeat, P., Beckmann, J.S., Lefranc, G., 1999, Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IkappaB alpha/NF-kappaB pathway in limb-girdle muscular dystrophy type 2A, Nat Med., 5, 503–11
Baier, L.J., Permana, P.A., Yang X., Pratley, R.E., Hanson, R.L., Shen, G.Q., Mott, D., Knowler, W.C., Cox, N.J., Horikawa, Y., Oda, N., Bell, G.I., Bogardus, C., 2000, A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance, J. Clin. Invest., 106, 69–73
Baki, A., Tompa, P., Molnár, O., Friedrich, P., 1995, Autolysis parallels activation of μ -calpain, Biochem. J., 318, 897–901
Banik, N.L., Matzelle, D., Terry, E., Hogan, E.L., 1997, A new mechanism of methylprednisolone and other corticosteroids action demonstrated in vitro: inhibition of a proteinase (calpain) prevents myelin and cytoskeletal protein degradation, Brain. Res.; 748,,205–210
Bano, D., Young, K.W., Guerin, C.J., LeFeuvre, R., Rothwell, N.J. ,Naldini, L., Rizzuto, R., Carafoli, E. and Nicotera, P., 2005, Cleavage of the plasma membrane Na(+)/Ca(2+) exchanger in excitotoxicity, Cell ,120, 275–285
Bansal, D., and Campbell, K.P., 2004, Dysferlin and the plasma membrane repair in muscular dystrophy, Trends Cell Biol., 14, 206–213
Bashir, R., Britton, S., Strachan, T., Keers, S., Vafiadaki, E., Lako, M., Richard, I., Marchand, S., Bourg, N., and Argov, Z., et al., 1998, A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B, Nat. Genet., 20, 37–42
Beckmann, J.S., Richard, I., Hillaire, D., Broux, O., Antignac, C., Bois, E., Cann, H., Cottingham, R.W., Feingold, N., and Feingold, J., et al.,1991, A gene for limb-girdle muscular dystrophy maps to chromosome 15 by linkage , C. R. Acad. Sci. III, 312, 141–148
Besse, S., Delcayre, C., Chevalier, B., Hardouin, S., Heymes, C., Bourgeois, F., Moalic, J.M., Swynghedauw, B., 1994, Is the senescent heart overloaded and already failing, Cardiovasc. Drugs Ther., 8, 581–587
Blalock, E.M., Porter, N.M., Landfield, P.W., 1999, Decreased G-protein-mediated regulation and shift in calcium channel types with age in hippocampal cultures, J. Neurosci, 19, 8674–8684
Blanchard, H., Li, Y., Cygler, M., Kay, C.M., Simon, J., Blanchard, H., Li, Y., Cygler, M., Kay, C.M., Simon, J.C., Davies, P.L., Elce, J. S., 1996, Ca(2+)-binding domain VI of rat calpain is a homodimer in solution: hydrodynamic, crystallization and preliminary X-ray diffraction studies, Protein Sci., 5, 535–537
Blomgren, K., Zhu, C., Wang, X., et al., 2001, Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia: a mechanism of “pathological apoptosis”?, J. Biol. Chem., 276, 10191–10198
Branca, D., Gigliucci, A., Bano, D., Brini, M., Carafoli, E., 1999, Expression, partial purification and functional properties of the muscle specific calpain isoform p94, Eur. J. Biochem., 265, 839–46
Buee, L., Bussiere, T., Buee-Scherrer, V., Delacourte, A., Hof, P.R., 2000, Tau protein isoforms, phosphorylation and role in neurodegenerative disorders, Brain. Res. Rev., 33, 95–130
Bushby, K.M.D., 1999, Making sense of the limb-girdle muscular dystrophies, Brain,122, 1403–1420
Butler, A.E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R.A., and Butler, P.C., 2003, Þ-Cell Deficit and Increased Þ-Cell Apoptosis in Humans With Type 2 Diabetes, Diabetes, 52, 102–110
Cai, D., Frantz, J.D., Tawa, N.E., P.A. Jr., Melendez, B.C., Oh, H.G., Lidov, P.O., Hasselgren, W.R., Frontera, J. and Lee, D.J. et al., 2004, IKKbeta/NF-kappaB activation causes severe muscle wasting in mice, Cell ,119 ,,285–298
Carafoli, E., and Molinari, M., 1998, Calpain: a protease in search of a function?, Biochem. Biophys. Res. Commun., 247, 193–203.
Chae, J., Minami, N., Jin, Y., Nakagawa, M., Murayama, K., Igarashi, F. and Nonaka, I., 2001, Calpain 3 gene mutations: genetic and clinical-pathologic findings in limb-girdle muscular dystrophy, Neuromuscul. Dis., 11, 547–555
Chen, M., and Fernandez, H.L., 2005, Mu-calpain is functionally required for alpha-processing of Alzheimer’s beta-amyloid precursor protein, Biochem. Biophys. Res. Commun., 330, 714–21
Chrobakova, T., Hermanova, M., Kroupova, I., Vondracek, P., Marikova, T., Mazanec, R., Zamecnik, J., Stanek, J., Havlova, M. and Fajkusova, L., 2004, Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome, Neuromuscul. Disord., 14, 659–665
Coolican, S., and Hathaway, D., 1984, Effect of L-alpha-phosphatidylinositol on a vascular smooth muscle Ca 2+ -dependent protease, J. Biol. Chem. , 259, 11627–11630
Cottin, P., Thompson, V., Sathe, S., Szpacenko, A., Goll, D., 2001, Autolysis of ν - and m-calpain from bovine skeletal muscle, Biol. Chem., 382, 767–776
Crocker, S.J., Smith, P.D., Jackson-Lewis, V., Lamba, W.R., Hayley, S.P., Grimm, E., Callaghan, S.M., Slack, R.S., Melloni, E., Przedborski, S., Robertson, G.S., Anisman, H., Merali, Z., Park, D.S., 2003, Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson’s disease, J. Neurosci., 23, 4081–4091
Dayton, W., Goll, D., Zeece, M., Robson, R., Reville, W., 1976, A Ca 2+ -activated protease possibly involved in myofibrillar protein turnover. Purification from porcine muscle, Biochemistry, 15, 2150–2158
Dear, T.N., and Boehm, T., 2000, Identification and characterization of two novel calpain large subunit genes, Gene , 274, 245–252
Dear, T.N., and Boehm, T., 1999, Diverse mRNA expression patterns of the mouse calpain genes Capn5, Capn6, and Capn 11 during development, Mech. Dev., 89, 201–209
Diaz, B., Moldoveanu, T., Kuiper, M., Campbell, R., Davies, P., 2004, Insertion Sequence 1 of Muscle-specific Calpain, p94, Acts as an Internal Propeptide, J. Biol. Chem., 279, 27656–27666
Fanin, M., Nascimbeni, A.C., Fulizio, L., Trevisan, C.P., Meznaric-Petrusa, M. and Angelini, C., 2003, Loss of calpain-3 autocatalytic activity in LGMD2A patients with normal protein expression, Am. J. Pathol., 163, 1929–1936
Fokkema, I.F., den Dunnen, J.T., and Taschner, P.E., 2005, LOVD: easy creation of a locus-specific sequence variation database using an “LSDB-in-a-box” approach , Hum.Mutat., 26, 63–68
Fougerousse, F., Gonin, P., Durand, M., Richard, I. and Raymackers, J.M., 2003, Force impairment in calpain 3-deficient mice is not correlated with mechanical disruption, Muscle Nerve, 27, 616–623
Garcia Diaz, B.E, Gauthier, S., Davies, PL., 2006, Ca 2+ dependency of calpain 3 (p94) activation, Biochemistry, 45, 3714–22
Garvey, S.M., Rajan, C., Lerner, A.P., Frankel, W.N. and Cox, G.A., 2002, The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin, Genomics, 79, 146–149
Gil-Parrado, S., Fernàndez-Montalvàn, A., Assfalg-Machleidt, I., Popp, O., Bestvater, F., Holloschi, A., Knoch, T.A., Auerswald, E.A., Welsh, K., Reed, J.C., Fritz, H., Fuentes-Prior, P., Spiess, E., Salvesen, G.S., Machleidt, W., 2002, Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members, J. Biol. Chem., 277, 27217–27226
Gil-Parrado, S., Popp, O., Knoch, T., Zahler, T., Bestvater, F., Felgenträger, M., Holloschi, A., Fernàndez-Montalavan, A., Auerswald, D., Fritzh, H., Fluentes-Prior, P., Machleidt, W., Spiess, E., 2003, Subcellular localization and in vivo subunit interactions of ubiquitous ν -calpain, J. Biol. Chem., 278
Goll, D.E., Thompson, V.F., Li, H., Wei, W., and Cong, J., 2003, The Calpain System, Physiol. Rev., 83, 731–801
Gonzalez, A., Abril, E., Roca, A., Aragon, M.J., Figueroa, M.J., Velarde, P., Royo, J.L., Real, L.M., Ruiz, A., CAPN10 alleles are associated with polycystic ovary syndrome, J. Clin. Endocrinol. Metab., 87, 3971–3976
Gregorio, C., Granzier, H., Sorimachi, H., Labeit, S.,1999, Muscle assembly: a titanic achievement?, Curr. Opin. Cell. Biol., 11, 18–25
Griffin, M.E., Marcucci, M.J., Cline, G.W., Bell, K., Barucci, N., Lee, D., Goodyear, L.J., Kraegen, E.W., White, M.F., Shulman, G.I., 1999, Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 48, 1270–4
Guroff, G., 1964, A neutral, calcium-activated proteinase from the soluble fraction of rat brain, J. Biol. Chem., 239, 149–55
Guyon, J.R., Kudryashova, E., Potts, A., Dalkilic, I., Brosius, M.A., Thompson, T.G., Beckmann, J.S., Kunkel, L.M. and. Spencer M.J., 2003, Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans, Muscle Nerve, 28, 472–483
Hanis, C.L., Boerwinkle, E., Chakraborty, R., Ellsworth, D.L., Concannon, P., Stirling, B., Morrison, V.A., Wapelhorst, B., Spielman, R.S., Gogolin-Ewens, K.J., Shephard, J.M., Williams, S.R., Risch, N., Hinds, D., Iwasaki, N., Ogata, M, Omori, Y., Petzold, C., Rietzch, H., Schroder, H.E., Schulze, J., Cox, N.J., Menzel, S., Boriraj, V.V., and Chen, X., et al., 1996, A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2, Nat. Genet., 13 , 161–166
Haravuori, H., Vihola, A., Straub, V., Auranen, M., Richard, I., Marchand, S., Voit, T., Labeit, S., Somer, H. and Peltonen, L., et al., 2001 , Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene, Neurology, 56, 869–877
Harris, F., Chatfield, L., Singh, J., Phoenix, D.A., 2004, Role of calpains in diabetes mellitus: a mini review, Mol. Cell. Biochem., 261, 161–7
Hosfield, C., Elce, J., Davies, P., Jia Z., 1999, Crystal structure of calpain reveals the structural basis for Ca 2+ -dependent protease activity and a novel mode of enzyme activation, EMBO J., 18, 6880–6889
Hoffstedt, J., Naslund, E., Arner, P., 2002, Calpain-10 gene polymorphism is associated with Reduced Þ 3-Adrenoceptor function in human fat cells, J. Clin. Endocr. Metab., 87, 3362–3367
Horikawa, Y., Oda, N., Cox, N.J., et al., 2000, Genetic varation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus, Nat. Genet., 26, 163–165
Illa, I., Serrano-Munuera, C., Gallardo, E., Lasa, A., Rojas-Garcia, R., Palmer, J., Gallano, P., Baiget, M., Matsuda, C., and Brown, R.H., 2001, Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype, Ann. Neurol., 49, 130–134
Inomata, M., Saito, Y., Kon, K., Kawashima, S., 1990, Binding sites for calcium-activated neutral protease on erythrocyte membranes are not membrane phospholipids. Biochem.Biophys. Res. Commun., 171, 625–632
Jia, Z., Petrounevitch, V., Wong, A., Moldoveanu, T., Davies, P.L., Elce, J.S., and Beckmann, J.S., 2001, Mutations in calpain 3 associated with limb girdle muscular dystrophy: analysis by molecular modeling and by mutation in m-calpain, Biophys. J., 80, 2590–2596
Johnson, J.D., Ahmed, N.T., Luciani, D. S., Han, Z., Tran, H., Fujita, J., Misler, S., Edlund, H., and Polonsky, K.S., 2003, Increased islet apoptosis in Pdx1+/– mice, J. Clin. Invest., 111, 1147–1160
Jordàn, J., Galindo, M.F., Miller, R.J.,1997, Role of calpain- and interleukin-1 beta converting enzyme-like proteases in the beta-amyloid-induced death of rat hippocampal neurons in culture, J. Neurochem., 68, 1612–1621
Saito, K., Elce, J.S., Hamos, J.E., and Nixon, R.A., 1993, Widespread Activation of Calcium-Activated Neutral Proteinase (Calpain) in the Brain in Alzheimer Disease: A Potential Molecular Basis for Neuronal Degeneration, Proc. Natl. Acad. Sci. U. S. A., 90, 2628–2632
Kawai, H., Akaike, M., Kunishige, M., Inui, T., Adachi, K., Kimura, C., Kawajiri, M., Nishida, Y., Endo, I., and Kashiwagi, S. et al., 1998, Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families , Muscle Nerve, 21, 1493–1501
Kim, M.J., Jo, D.G., Hong, G.S., Kim, B.J., Lai, M., Cho, D.H., Kim, K.W., Bandyopadhyay, A., Hong, Y.M., Kim, D.H., Cho, C., Liu, J.O., Snyder, S.H., Jung, Y.K., 2002, Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death, Proc. Natl. Acad. Sci. USA, 99, 9870–9875
Kinbara, K., Ishiura, S., Tomioka, S., Sorimachi, H., Jeong, S.Y., Amano, S., Kawasaki, H., Kolmerer, B., Kimura, S., Labeit, S., Suzuki, K., 1998 , Purification of native p94, a muscle-specific calpain, and characterization of its autolysis, Biochem J., 335, 589–96
Kinbara, K., Sorimachi, H., Ishiura, S., Suzuki, K., 1997, Muscle-specific calpain, p94, interacts with the extreme C-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs, Arch. Biochem. Biophys, 342, 99–107
Kotaka, M., Kostin, S., Ngai, S., Chan, K., Lau, Y., Lee, S.M., Li H., Ng, E.K., Schaper, J., Tsui SK, Fung K, Lee C, Waye MM. ,2000,Interaction of hCLIM1, an enigma family protein, with alpha-actinin 2.,J. Cell. Biochem. ,78,,558–65
Kotaka, M., Lau, Y.M., Cheung, K.K., Lee, S.M., Li, H.Y., Chan, W.Y., Fung, K.P., Lee, C.Y., Waye, M.M., Tsui, S.K., 2001, Elfin is expressed during early heart development, 83, 463–72
Kramerova, I., Kudryashova E., Venkatraman, G., and Spencer, M.J., 2005, Calpain 3 participates in muscle remodeling by acting upstream of the ubiquitin-proteasome pathway, Hum. Mol. Genet., 14, 2125–2134
Kuboki, M; Ishii, H; Kazama, M., 1990, Characterization of calpain I-binding proteins in human erythrocyte plasma membrane, J. Biochem., 107, 776–780
Kuboki, M., Ishii, H., and Kazama, M., 1987, Procalpain is activated on the plasma membrane and the calpain acts on the membrane, Biochim. Biophys. Acta, 929, 164–172
Labeit, S., Kolmerer, B., 1995, Titins: giant proteins in charge of muscle ultrastructure and elasticity, Science, 270, 293–296
Lankiewicz, S., Luetjens, C.M., Nguyen, T.B., Krohn, A.J., Poppe, M., Cole, G.M., Saido, T.C., Prehn, J.H.M., 2000, Activation of calpain I converts excitotoxic neuron death into a caspase-independent cell death, J. Biol. Chem., 275, 17064–17071
Lee, W. J., Adachi, Y., Maki, M., Hatanaka, M., and Murachi, T., 1990, Factors influencing the binding of calpain I to human erythrocyte inside-out vesicles, Biochem. Int., 22, 163–171
Liu, J., Aoki, M., Illa, I., Wu, C., Fardeau, M., Angelini, C., Serrano, C., Urtizberea, J.A., Hentati, F., and Hamida, M.B., et al., 1998, Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy, Nat. Genet., 20, 31–36
Logie, L.J., Brown, A.E., Yeaman, S.J., Walker, M., 2005, Calpain inhibition and insulin action in cultured human muscle cells, Mol. Genet. Metab, 85, 54–60
Lynn, S., Evans, J.C., White, C.B., Frayling, T.M., Hattersley, A.T., Turnbull, D.M., Horikawa, Y., Cox, N.J., Bell, G.I., and Walker, M. , 2002, Variation in the calpain-10 gene affects blood glucose levels in the British population, Diabetes, 51, 247–250
Ma, H., Fukiage, C., Kim, Y.H., Duncan, M.K., Reed, N.A., Shih, M., Azuma, M., and Shearer, T.S., 2001, Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization, J. Biol. Chem., 276, 28525–28531
Marshall, C., Hitman, G.A., Partridge, C.J., Clark, A., Ma, H., Shearer, T.R., Turner, M.D., 2005, Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic beta-cells, Mol. Endocrinol., 19, 213–24
Mathews, P.M., Jiang, Y., Schmidt, S.D., Grbovic, O.M., Mercken, M., Nixon, R.A., 2002, Calpain activity regulates the cell surface distribution of amyloid precursor protein. Inhibition of calpains enhances endosomal generation of B-cleaved C-terminal APP fragments, J. Biol. Chem., 277, 36415–36424
Mcclelland, P., Lash, J., Hataway, D., 1989, Identification of major autolytic cleavage sites in the regulatory subunit of vascular Calpain II. A comparison of partial amino-terminal sequences to deduced sequence from complementary DNA, J. Biol. Chem., 264, 17428–17431
Mellgren, R., Song, K., Mericle, M., 1993, m-Calpain requires DNA for activity on nuclear proteins at low calcium concentrations, J. Biol. Chem., 268, 653–657
Melloni, E., Michetti, M., Salamino, F., Pontremoli, S., 1998, Molecular and functional properties of a calpain activator protein specific for ν -isoforms, J. Biol. Chem., 273, 12827–12831
Moldoveanu, T., Hosfield, C., Lim, D., Elce, J., Jia, Z., Davies, P., 2002, A Calcium switch aligns the active site of calpain, Cell, 108, 649–660
Mouatt-Prigent, A., Karlsson, J.O., Agid, and Hirsch E.C., 1996, Increased M-calpain expression in the mesencephalon of patients with Parkinson’s disease but not in other neurodegenerative disorders involving the mesencephalon: a role in nerve cell death, Neuroscience, 73, 979–987
Mundo, E., Soldati, L., Bellodi, L., Bianchi, G., 1997, The calpain-calpastatin system in obsessive-compulsive disorder, Biol. Psychiatry; 42, 228–229
Nath, R., Davis, M., Probert, A.W., Kupina, N.C., Ren, X., Schielke, G.P., Wang, K.K.W., 2000, Processing of cdk5 Activator p35 to Its Truncated Form (p25) by Calpain in Acutely Injured Neuronal Cells, Biochem. Biophys. Res. Commun., 274, 16–21
Nixon, R.A., Mohan, P., 1999, Calpains in the pathogenesis of Alzheimer’s disease. in: Wang KKW, Yuen P-W, eds. Calpain: pharmacology and toxicology of calcium-dependent protease. Philadelphia: Taylor & Francis, 267–91
Okitani, A., Goll, D., Stromer, M., Robson, R., Intracellular inhibitor of a Ca 2+ -dependent proteinase involved in myofibrillar protein turnover, Federation Proc., 35, 1746
Ono, Y., Sorimachi, H., Suzulu, K., 2004, Structure, Activation, and Biology of Calpain, Biochem. Biophys. Res. Commun, 245, 284–294
Ono, Y., Shimada, H., Sorimachi, H., Richard, I., Saido, T.C., Beckmann, J.S., Ishiura, S., and Suzuki, K., 1998, Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A, J. Biol. Chem., 273, 17073–17078
Ono, Y., Torii, F., Ojima, K., Doi, N., Yoshioka, K., Kawabata, Y., Labeit, D., Labeit, S., Suzuki, K., Abe, K., Maeda, T., Sorimachi, H., 2006, Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a genetic reporter system, J. Biol. Chem., 281, 18519–31
Orho-Melander, M., Klannemark, M., Svensson, M.K., Ridderstrale, M., Lindgren, C.M., and Groop, L., 2002, Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels, Diabetes, 51, 2658–2664
Otani, K., Han, D.H., Ford, E.L., Garcia-Roves, P.M., Ye, H., Horikawa, Y., Bell, G.I., Holloszy, J.O., Polonsky, K.S., 2004, Calpain system regulates muscle mass and glucose transporter GLUT4 turnover, J. Biol. Chem., 279, 20915–2
Otani, K., Polonsky, K.S., Holloszy, J.O., Han, D.H., 2006, Inhibition of calpain results in impaired contraction-stimulated GLUT4 translocation in skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 291, 544–8
Papp, Z., van der Velden, J., Stienen, G.J., 2000, Calpain-I induced alterations in the cytoskeletal structure and impaired mechanical properties of single myocytes of rat heart,. Cardiovasc. Res., 45, 981–993
P.F. van der Ven, Wiesner, S., Salmikangas, P., Auerbach, D., Himmel, M., Kempa, S., Hayess, K., Pacholsky, D., Taivainen, A., and Schröder, R., et al., 2000, Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin, J. Cell Biol., 151, 235–248
Pintèr, M., and Friedrich, P., 1988, The calcium dependent proteolytic system calpain-calpatatin in Drosophila melanogaster, Biochem J., 253, 467–473
Pintèr, M., Stierandova, A., and Friedrich, P., 1992, Purification and characterization o a Ca 2+ activated thiol protease from drosophila melanogaster, Biochemistry, 31, 8201–8206
Pontremoli, S., Melloni, E., Michetti, M., Salamino, F., Sparatore, B., Horecker, B., 1988, An endogenous activator of the Ca 2+ -dependent proteinase of human neutrophils that increases its affinity for Ca 2+ , Proc. Natl. Acad. Sci., USA, 85, 1740–1743
Pontremoli, S., Melloni, E., Viotti, PL., Michetti, M., Di Lisa, F., Siliprandi, N., 1990, Isovalerylcarnitine is a specific activator of the high calcium requiring calpain forms, Biochem. Biophys. Res. Commun., 167, 373–380
Pontremoli, S., Viotti P., Michetti, M., Sparatore, B., Salamino, F., Melloni, E., 1990, Identification of an endogenous activator of calpain in rat skeletal muscle, Biochem. Biophys. Res. Commun., 171, 569–574
Rey, M., and Davies, P., 2002, The protease core of the muscle-specific calpain, p94, undergoes Ca 2+ -dependent intramolecular autolysis, FEBS Lett., 532, 401–6
Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J.A., Fardeau, M., Jackson, C.E., Cohen, D., and Beckmann, J.S., 1995, Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A, Cell, 81, 27–40
Richard, I., Roudant, C., Saenz, A., et al., 1999, Calpainopathy, a survey of mutations and polymorphism, Am. J. Hum. Genet., 64, 1524–1540
Rizo, J., and Sudhof, T.C., 1998, C2-domains, structure and function of a universal Ca 2+ -binding domain, J. Biol. Chem., 273, 15879 –15822
Romero, P.J., Salas, V., Hernandez, C.,,2002,Calcium pump phosphoenzyme from young and old human red cells.,,26,,945–949
Saito, K., Elce, J.S., Hamos, J.E., Nixon, R.A., 1993, Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration, Proc. Natl. Acad. Sci. U.S.A., 90, 2628–2632
Saido, T., Shibata, M., Takenawa, T., Murofushi, H., Suzuki, K., 1992, Positive regulation of ν -calpain action by polyphosphoinositides, J. Biol. Chem., 267, 24585–24590
Sandmann, S., Yu, M., Unger, T., 2001, Transcriptional and translational regulation of calpain in the rat heart after myocardial infarction – effects of AT(1) and AT(2) receptor antagonists and ACE inhibitor, Br. J. Pharmacol.; 132, 767–777
Sedarous, M., Keramaris, E., O’Hare, M., Melloni, E., Slack, R.S., Elce, J.S., Greer, P.A., Park, D.S., 2003, Calpains mediate p53 activation and neuronal death evoked by DNA damage, J. Biol. Chem., 278, 26031–26038
Shearer, T.R., Ma, H., Shih, M., Fukiage, C., Azuma, M., 2000, Calpains in the lens and cataractogenesis, Methods Mol. Biol.; 144, 277–285
Shields, D.C., Schaecher, K.E., Saido, T.C., Banik, N.L., 1999, A putative mechanism of demyelination in multiple sclerosis by a proteolytic enzyme, calpain, Proc. Natl. Acad. Sci. U S A; 96,11486–11491
Shollmeyer, J., 1986, Possible role of calpain I and calpain II in differentiating muscle, Exp. Cell. Res., 163, 413–422
Shollmeyer, J., 1986, Role of Ca 2+ and Ca 2+ -activated protease in myoblast fusion, Exp. Cell. Res.,162, 411–422
Sokol, S.B., and Kuwabara, P.E., 2000, Proteolysis in Caenorhabditis elegans sex determination: cleavage of TRA-2A by TRA-3, Genes.Dev., 14, 901–906
Sorimachi, H., Forsberg, N.E., Lee, H.J., Joeng, S.Y., Richard, I., Beckmann, J.S., Ishiura, S., and Suzuki, K., 1996, Highly conserved structure in the promoter region of the gene for muscle-specific calpain, p94, Biol. Chem., 377, 859–864
Sorimachi, H., Imajoh, O.S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., and Suzuki, K., 1989, Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types. Specific expression of the mRNA in skeletal muscle, J. Biol. Chem., 264, 20106–20111
Sorimachi, H., Ohmi, S., Emori, Y., Kawasaki, H., Saido, T., Ohno, S., Minami, Y., Suzuki, K., 1990, A novel member of the calcium-dependent cysteine protease family, Biol. Chem. Hoppe Seyler., 371, 171–6
Sorimachi, H., Ono, Y., Suzuki, K., 2000, Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A, Adv. Exp. Med. Biol., 481, 383–95
Sorimachi, H., and Suzuki, K., 2001, The structure of calpain, J. Biochem., 129, 653–654
Sorimachi, H., Toyama-Sorimachi, N., Saido, T. C., Kawasaki, H., Sugita, H., Miyasaka, M., Arahata, K., Ishiura, S., Suzuki, K., 1993, Muscle-specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle, J. Biol. Chem., 268, 10593–10605
Stossel, T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M., and Shapiro, S.S., 2001, Filamins as integrators of cell mechanics and signalling, Nat. Rev. Mol. Cell. Biol., 2, 138–145
Strobl, S., Fernandez-Catalan, C., Braun, M., Huber, R., Masumoto, H., Nakagawa, K., Irie, A., Sorimachi, H., Bourenkow, G., Bartunik, H., Suzuki, K., Bode, W., 1999, The crystal structure of calcium free human m-calpain suggests an electrostatic switch mechanism for activation by calcium, PNAS, 97, 588–592
Sugimoto, K., Katsuya, T., Ishikawa, K., Iwashima, Y., Yamamoto, K., Fu, Y., Matsuo, A., Motone, M., Rakugi, H., Ogihara, T., 2003, UCSNP-43 G/A polymorphism of calpain-10 gene is associated with hypertension and dyslipidemia in Japanese population, Am. J. Hypertens., 16, A82
Suzuki, K., Hata, S., Kawabata, Y., Sorimachi, H.,. Structure, activation, and biology of calpain, 2004, Diabetes, ;53, 12–8.
Suzuki, K., Tsuji, S., Kubota, S., Kimura, Y., Imahori, K., 1981, Limited autolysis of Ca 2+ -activated neutral protease (CANP) changes its sensitivity to Ca 2+ ions, J. Biochem., 90, 275–278
Taveau, M., Bourg, N., Sillon, G., Roudaut, C., Bartoli, M., and Richard, I., 2003, Calpain 3 is activated through autolysis within the active site and lyses sarcomeric and sarcolemmal components, Mol. Cell. Biol., 23, 9127–9135
Thompson, T.G., Cha, Y.M., Hack, A.A., Brosius, M., Rajala, M., Lidov, H.G., McNally, E.M., Watkins, S., and Kunkel, L.M., 2000, Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting protein, J. Cell Biol., 148, 115–126
Thompson, V.F., and Goll, D.E., 2000, Purification of mu-calpain, m-calpain, and calpastatin from animal tissues, Methods. Mol. Biol., 144, 3–16
Tidball, J.G, Spencer, M.J., 2000, Calpains and muscular dystrophies, Int. J. Biochem. Cell. Biol.; 32, 1–5
Tompa, P., Emori, Y., Sorimachi, H., Suzuki, K., Friedrich, P., 2001, Domain III of calpain is a Ca 2+ -regulated phospholipid-binding domain, Biochem. Biophys. Res. Commun., 280, 1333–1339
Tompa, P., Mucsi, Z., Orosz, G., Friedrich, P., 2002, Calpastatin subdomains A and C are activators of calpain, J. Biol. Chem., 277, 9022–6
Tsuji, T., Ohga, Y., Yoshikawa, Y., et al., 2001, Rat cardiac contractile dysfunction induced by Ca 2+ overload: possible link to the proteolysis of alpha-fodrin, Am. J. Physiol. Heart. Circ. Physiol., 281, 1286–1294
Tsuji, T., Shimohama, S., Kimura, J., Shimizu, K., 1998, m-Calpain (calcium-activated neutral proteinase) in Alzheimer’s disease brains, Neurosci. Lett.; 248, 109–112
Vanderklish, P.W., and Bahr, B.A., 2000, The pathogenic activation of calpain: a marker and mediator of cellular toxicity and disease states, Int. J. Exp. Path., 81, 323–339
Vorgerd, M., P.F., van der Ven, Bruchertseifer, M., Lowe, T., Kley, R.A., Schroder, R., Lochmuller, H., Himmel, M., Koehler, K., and Furst, D.O., et al., 2005, A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy, Am. J. Hum. Genet., 77, 297–304
Walton, J.N., and Nattrass, F.J., 1954, On the classification, natural history and treatment of the myopathies, Brain, 77, 169–231
Wang, K.K.W., 2000, Calpain or caspase: can you tell the difference?, Trends. Neurosci., 23, 20–26
Wood, D.E., Thomas, A., Devi, L.A., Berman, Y., Beavis, R.C., Reed, J.C., Newcomb, E.W., 1998, Bax cleavage is mediated by calpain during drug-induced apoptosis, Oncogene, 17, 1069–1078
Xiao, G., Rabson, A.B., Young, W., Qing, G., Qu, Z., 2006, Alternative pathways of NF-kappaB activation: a double-edged sword in health and disease, Cytokine Growth Factor Rev., 17, 281–93
Xu, K., Driscoll, M., Tavernarakis, N., 2002, Specific aspartyl and calpain proteases are required for neurodegeneration in C, elegans, Nature , 419, 939–944
Yoshida, K., Inui, M., Harada, K., et al., 1995, Reperfusion of rat heart after brief ischemia induces proteolysis of calspectin (nonerythroid spectrin or fodrin) by calpain, Circ. Res., 77, 603–610
Yoshikawa, Y., Mukai, H., Hino, F., Asada, K., Kato, I., 2000, Isolation of two novel genes, down-regulated in gastric cancer, Jpn. J. Cancer Res.; 91,,459–463
Yoshizawa, T., Sorimachi, H., Tomioka, S., Ishiura, S., Suzuki, K., 1995, Calpain dissociates into subunits in the presence calcium ions, Biochem. Biophys. Res. Commun., 208, 376–383
Zatz, M., Vainzof, M., Passos-Bueno, M.R., 2000, Limb-girdle muscular dystrophy: one gene with different phenotypes, one phenotype with different genes, Curr. Opin. Neurol., 13, 511–517
Zimmerman, U., and Schlapfer, W., 1991, Two stage autolysis of the catalytic subunit initiates activation of calpain I, Biochim. Biophys. Acta, 1078, 192–198
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer
About this chapter
Cite this chapter
BERTIPAGLIA, I., CARAFOLI, E. (2007). Calpains and Human Disease. In: Carafoli, E., Brini, M. (eds) Calcium Signalling and Disease. Subcellular Biochemistry, vol 45. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6191-2_2
Download citation
DOI: https://doi.org/10.1007/978-1-4020-6191-2_2
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-6190-5
Online ISBN: 978-1-4020-6191-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)