Share This Article:

New Caspases’ inhibitors belonging to the serpin superfamily: A novel key control point of apoptosis in mammalian tissues

Abstract Full-Text HTML Download Download as PDF (Size:1071KB) PP. 740-750
DOI: 10.4236/abb.2012.326095    4,268 Downloads   7,409 Views   Citations

ABSTRACT

The present report overviews a new family of bovine serpins able to inhibit pseudo-irreversibly initiator and effector caspases, a group of cysteine proteases in charge of cell dismantling during apoptosis, a finely regulated cell death process. The 8 members identified at the gene level showed a high homology with human SERPINA3 and were therefore designed bovSERPINA3-1 to A3-8. At least six of them are able to inhibit caspases. Two of them (bovSERPINA3-1 and A3-3) have been purified from bovine muscle and extensively investigated during these last years. After a general presentation of the serpin superfamily, the kinetic aspects of their interaction with human cas-pases 3 and 8 were studied and findings obtained suggest that caspases could be their target enzymes in living cells. In muscle and primary myoblast in culture, they showed an intracellular localization and because of their high level in blood, they can be exported. Two biological functions (potential regulator of apoptosis and expression during myoblast differentiation) were investigated and it was concluded that they are very likely a efficient regulator of apoptosis, a proposal supported by their high expression in proliferating myoblast (cell survival is essential during this differentiation phase) but not in myotubes.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Gagaoua, M. , Boudida, Y. , Becila, S. , Picard, B. , Boudjellal, A. , Sentandreu, M. and Ouali, A. (2012) New Caspases’ inhibitors belonging to the serpin superfamily: A novel key control point of apoptosis in mammalian tissues. Advances in Bioscience and Biotechnology, 3, 740-750. doi: 10.4236/abb.2012.326095.

References

[1] Taylor, R. C., Cullen, S. P., and Martin, S. J. (2008) Apoptosis: controlled demolition at the cellular level, Nat Rev Mol Cell Bio,9, 231-241. Doi:10.1038/Nrm2312
[2] Hengartner, M. O. (2000) The biochemistry of apoptosis, Nature,407, 770-776. Doi:10.1038/35037710
[3] Sirzen, F., Zhivotovsky, B., Nilsson, A., Bergh, J., and Lewensohn, R. (1998) Higher spontaneous apoptotic index in small cell compared with non-small cell lung carcinoma cell lines; lack of correlation with Bcl-2/Bax, Lung Cancer,22, 1-13.
[4] Fuentes-Prior, P., and Salvesen, G. S. (2004) The protein structures that shape caspase activity, specificity, activation and inhibition, Biochem J,384, 201-232. Doi:10.1042/BJ20041142
[5] Philchenkov, A. (2004) Caspases: potential targets for regulating cell death, J Cell Mol Med,8, 432-444.
[6] Saelens, X., Festjens, N., Vande Walle, L., van Gurp, M., van Loo, G., and Vandenabeele, P. (2004) Toxic proteins released from mitochondria in cell death, Oncogene,23, 2861-2874. Doi:10.1038/sj.onc.1207523
[7] Annand, R. R., Dahlen, J. R., Sprecher, C. A., De Dreu, P., Foster, D. C., Mankovich, J. A., Talanian, R. V., Kisiel, W., and Giegel, D. A. (1999) Caspase-1 (interleukin-1beta-converting enzyme) is inhibited by the human serpin analogue proteinase inhibitor 9, Biochem J,3, 655-665.
[8] Law, R. H., Zhang, Q., McGowan, S., Buckle, A. M., Silverman, G. A., Wong, W., Rosado, C. J., Langendorf, C. G., Pike, R. N., Bird, P. I., and Whisstock, J. C. (2006) An overview of the serpin superfamily, Genome biology,7, 216. Doi:10.1186/gb-2006-7-5-216
[9] Silverman, G. A., Bird, P. I., Carrell, R. W., Church, F. C., Coughlin, P. B., Gettins, P. G., Irving, J. A., Lomas, D. A., Luke, C. J., Moyer, R. W., Pemberton, P. A., Remold-O'Donnell, E., Salvesen, G. S., Travis, J., and Whisstock, J. C. (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature, J Biol Chem,276, 33293-33296. Doi:10.1074/jbc.R100016200
[10] Gettins, P. G. (2002) Serpin structure, mechanism, and function, Chem Rev,102, 4751-4804. Doi:10.1021/cr010170+
[11] Elliott, P. R., Pei, X. Y., Dafforn, T. R., and Lomas, D. A. (2000) Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease, Protein science : a publication of the Protein Society,9, 1274-1281. Doi:10.1110/ps.9.7.1274
[12] Silverman, G. A., Whisstock, J. C., Bottomley, S. P., Huntington, J. A., Kaiserman, D., Luke, C. J., Pak, S. C., Reichhart, J. M., and Bird, P. I. (2010) Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems, J Biol Chem,285, 24299-24305. Doi:10.1074/jbc.R110.112771
[13] Whisstock, J. C., Silverman, G. A., Bird, P. I., Bottomley, S. P., Kaiserman, D., Luke, C. J., Pak, S. C., Reichhart, J. M., and Huntington, J. A. (2010) Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions, J Biol Chem,285, 24307-24312. Doi:10.1074/jbc.R110.141408
[14] Engh, R., Lobermann, H., Schneider, M., Wiegand, G., Huber, R., and Laurell, C. B. (1989) The S variant of human alpha 1-antitrypsin, structure and implications for function and metabolism, Protein Eng,2, 407-415.
[15] Ye, S., Cech, A. L., Belmares, R., Bergstrom, R. C., Tong, Y., Corey, D. R., Kanost, M. R., and Goldsmith, E. J. (2001) The structure of a Michaelis serpin-protease complex, Nat Struct Biol,8, 979-983. Doi:10.1038/nsb1101-979
[16] Huntington, J. A., Read, R. J., and Carrell, R. W. (2000) Structure of a serpin-protease complex shows inhibition by deformation, Nature,407, 923-926.
[17] Herrera-Mendez, C. H., Becila, S., Blanchet, X., Pelissier, P., Delourme, D., Coulis, G., Sentandreu, M. A., Boudjellal, A., Bremaud, L., and Ouali, A. (2009) Inhibition of human initiator caspase 8 and effector caspase 3 by cross-class inhibitory bovSERPINA3-1 and A3-3, FEBS letters,583, 2743-2748.Doi:10.1016/j.febslet.2009.07.055
[18] Tassy, C., Herrera-Mendez, C. H., Sentandreu, M. A., Aubry, L., Bremaud, L., Pelissier, P., Delourme, D., Brillard, M., Gauthier, F., Leveziel, H., and Ouali, A. (2005) Muscle endopin 1, a muscle intracellular serpin which strongly inhibits elastase: purification, characterization, cellular localization and tissue distribution, Biochem J,388, 273-280. Doi: 10.1042/BJ20041921
[19] Herrera-Mendez, C. H., Bremaud, L., Coulis, G., Pelissier, P., Sentandreu, M. A., Aubry, L., Delourme, D., Chambon, C., Maftah, A., Leveziel, H., and Ouali, A. (2006) Purification of the skeletal muscle protein Endopin 1B and characterization of the genes encoding Endopin 1A and 1B isoforms, FEBS letters,580, 3477-3484. Doi: 10.1016/j.febslet.2006.04.099
[20] Pelissier, P., Delourme, D., Germot, A., Blanchet, X., Becila, S., Maftah, A., Leveziel, H., Ouali, A., and Bremaud, L. (2008) An original SERPINA3 gene cluster: elucidation of genomic organization and gene expression in the Bos taurus 21q24 region, BMC genomics,9, 151. Doi: 10.1186/1471-2164-9-151
[21] Schechter, N. M., and Plotnick, M. I. (2004) Measurement of the kinetic parameters mediating protease-serpin inhibition, Methods,32, 159-168.
[22] Horvath, A. J., Lu, B. G., Pike, R. N., and Bottomley, S. P. (2011) Methods to measure the kinetics of protease inhibition by serpins, Methods Enzymol,501, 223-235. Doi: 10.1016/B978-0-12-385950-1.00011-0
[23] Dobo, J., Swanson, R., Salvesen, G. S., Olson, S. T., and Gettins, P. G. (2006) Cytokine response modifier a inhibition of initiator caspases results in covalent complex formation and dissociation of the caspase tetramer, J Biol Chem,281, 38781-38790. Doi: 10.1074/jbc.M605151200
[24] Stennicke, H. R., Ryan, C. A., and Salvesen, G. S. (2002) Reprieval from execution: the molecular basis of caspase inhibition, Trends Biochem Sci,27, 94-101.
[25] Swanson, R., Raghavendra, M. P., Zhang, W. Q., Froelich, C., Gettins, P. G. W., and Olson, S. T. (2007) Serine and cysteine proteases are translocated to similar extents upon formation of covalent complexes with serpins- Fluorescence perturbation and fluorescence resonance energy transfer mapping of the protease binding site in CrmA complexes with granzyme B and caspase-1, J Biol Chem,282, 2305-2313. Doi:10.1074/jbc.M609546200
[26] Blanchet, X., Pere-Brissaud, A., Duprat, N., Pinault, E., Delourme, D., Ouali, A., Combet, C., Maftah, A., Pelissier, P., and Bremaud, L. (2012) Mutagenesis of the bovSERPINA3-3 demonstrates the requirement of aspar-tate-371 for intermolecular interaction and formation of dimers, Protein science : a publication of the Protein Society,21, 977-986. Doi:10.1002/pro.2078
[27] Billingsley, G. D., Walter, M. A., Hammond, G. L., and Cox, D. W. (1993) Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1, Am J Hum Genet,52, 343-353.
[28] Forsyth, S., Horvath, A., and Coughlin, P. (2003) A review and comparison of the murine alpha1-antitrypsin and alpha1-antichymotrypsin multigene clusters with the human clade A serpins, Genomics,81, 336-345.
[29] Horvath, A. J., Forsyth, S. L., and Coughlin, P. B. (2004) Expression patterns of murine antichymotrypsin-like genes reflect evolutionary divergence at the serpina3 locus, Journal of molecular evolution,59, 488-497. Doi:10.1007/s00239-004-2640-9
[30] Musilova, P., Lahbib-Mansais, Y., Yerle, M., Cepica, S., Stratil, A., Coppieters, W., and Rubes, J. (1995) Assignment of pig alpha 1-antichymotrypsin (AACT or PI2) gene to chromosome region 7q23-q26, Mamm Genome,6, 445.
[31] Archibald, A. L., Couperwhite, S., Mellink, C. H., Lahbib-Mansais, Y., and Gellin, J. (1996) Porcine alpha-1-antitrypsin (PI): cDNA sequence, polymorphism and assignment to chromosome 7q2.4q26, Anim Genet,27, 85-89.
[32] Lamkanfi, M., Festjens, N., Declercq, W., Vanden Berghe, T., and Vandenabeele, P. (2007) Caspases in cell survival, proliferation and differentiation, Cell Death Differ,14, 44-55. Doi:10.1038/sj.cdd.4402047
[33] O'Riordan, M. X., Bauler, L. D., Scott, F. L., and Duckett, C. S. (2008) Inhibitor of apoptosis proteins in eukaryotic evolution and development: a model of thematic conservation, Dev Cell,15, 497-508. Doi:10.1016/j.devcel.2008.09.012
[34] Beere, H. M. (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways, Journal of Clinical Investigation,115, 2633-2639. Doi:10.1172/Jc126471
[35] Arrigo, A. P. (2005) Heat shock proteins as molecular chaperones, M S-Med Sci,21, 619-625.
[36] Deveraux, Q. L., and Reed, T. C. (1999) IAP family proteins-suppressors of apoptosis, Gene Dev,13, 239-252.
[37] Dean, E. J., Ranson, M., Blackhall, F., Holt, S. V., and Dive, C. (2007) Novel therapeutic targets in lung cancer: Inhibitor of apoptosis proteins from laboratory to clinic, Cancer Treat Rev,33, 203-212. Doi:10.1016/j.ctrv.2006.11.002
[38] Cassens, U., Lewinski, G., Samraj, A. K., von Bernuth, H., Baust, H., Khazaie, K., and Los, M. (2003) Viral modulation of cell death by inhibition of caspases, Archivum immunologiae et therapiae experimentalis,51, 19-27.
[39] Chinni, C., de Niese, M. R., Tew, D. J., Jenkins, A. L., Bottomley, S. P., and Mackie, E. J. (1999) Thrombin, a survival factor for cultured myoblasts, J Biol Chem,274, 9169-9174.
[40] Citron, B. A., Smirnova, I. V., Zoubine, M. N., and Festoff, B. W. (1997) Quantitative PCR analysis reveals novel expression of prothrombin mRNA and regulation of its levels in developing mouse muscle, Thromb Res,87, 303-313.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.