Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma

作者: René Thieme , Susanne Kurz , Marlen Kolb , Tewodros Debebe , Susanne Holtze

DOI: 10.1371/JOURNAL.PONE.0130470

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摘要: Background The naked mole-rat (NMR) is a long-lived and cancer resistant species. Identification of potential anti-cancer age related mechanisms great interest makes this species eminent to investigate strategies understand aging mechanisms. Since it known that the NMR expresses higher liver mRNA-levels alpha 2-macroglobulin than mice, nothing about its structure, functionality or expression level in compared human A2M. Results Here we show comprehensive analysis NMR- plasma-A2M, showing different prediction glycosylation NMR-A2M, which results molecular weight Additionally, found concentration A2M (8.3±0.44 mg/mL vs. 4.4±0.20 mg/mL) lower total plasma protein content (38.7±1.79 61.7±3.20 human. NMR-A2M can be transformed by methylamine trypsin resulting conformational change similar detectable polyclonal antibody against Determination tryptic anti-tryptic activity revealed plasma. On other hand, less proteolytic was Conclusion We binding specific receptor LRP1. could demonstrate LRP1 tissue but This accompanied EpCAM as central adhesion molecule progression. NMR-plasma capable increase fibroblast vitro most probably increasing CD29 expression. first report, demonstrating similarities well distinct differences between might directly linked intriguing phenotype suggests play an important role anti-aging NMR.

参考文章(59)
A. Seluanov, C. Hine, J. Azpurua, M. Feigenson, M. Bozzella, Z. Mao, K. C. Catania, V. Gorbunova, Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat Proceedings of the National Academy of Sciences of the United States of America. ,vol. 106, pp. 19352- 19357 ,(2009) , 10.1073/PNAS.0905252106
Alban Gaultier, Gabriel Simon, Sherry Niessen, Melissa Dix, Shinako Takimoto, Benjamin F. Cravatt, Steven L. Gonias, LDL receptor-related protein 1 regulates the abundance of diverse cell-signaling proteins in the plasma membrane proteome. Journal of Proteome Research. ,vol. 9, pp. 6689- 6695 ,(2010) , 10.1021/PR1008288
Reo Sekiguchi, Naoko T. Fujito, Masaru Nonaka, Evolution of the thioester-containing proteins (TEPs) of the arthropoda, revealed by molecular cloning of TEP genes from a spider, Hasarius adansoni. Developmental and Comparative Immunology. ,vol. 36, pp. 483- 489 ,(2012) , 10.1016/J.DCI.2011.05.003
Eugenio Mocchegiani, Laura Costarelli, Robertina Giacconi, Catia Cipriano, Elisa Muti, Marco Malavolta, Zinc-binding proteins (metallothionein and α-2 macroglobulin) and immunosenescence Experimental Gerontology. ,vol. 41, pp. 1094- 1107 ,(2006) , 10.1016/J.EXGER.2006.08.010
Sudesh Pawaria, Laura E. Kropp, Robert J. Binder, Immunotherapy of Tumors with α2-Macroglobulin-Antigen Complexes Pre-Formed In Vivo PLoS ONE. ,vol. 7, pp. e50365- ,(2012) , 10.1371/JOURNAL.PONE.0050365
STEVEN L. GONIAS, JONATHAN LaMARRE, KENDALL P. CROOKSTON, DONNA J. WEBB, BENI B. WOLF, M. BEATRIZ S. LOPES, HAROLD L. MOSES, M. ANTHONY HAYES, α2‐Macroglobulin and the α2‐Macroglobulin Receptor/LRP A Growth Regulatory Axisa Annals of the New York Academy of Sciences. ,vol. 737, pp. 273- 290 ,(1994) , 10.1111/J.1749-6632.1994.TB44318.X
G Birkenmeier, R Müller, K Huse, J Forberg, C Gläser, H Hedrich, S Nicklisch, A Reichenbach, Human α2-macroglobulin: genotype–phenotype relation Experimental Neurology. ,vol. 184, pp. 153- 161 ,(2003) , 10.1016/S0014-4886(03)00110-9
C. G. Faulkes, N. C. Bennett, M. W. Bruford, H. P. O'brien, G. H. Aguilar, J. U. M. Jarvis, Ecological constraints drive social evolution in the African mole-rats. Proceedings of The Royal Society B: Biological Sciences. ,vol. 264, pp. 1619- 1627 ,(1997) , 10.1098/RSPB.1997.0226
E.M. De Souza, M. Meuser-Batista, D.G. Batista, B.B. Duarte, T.C. Araújo-Jorge, M.N.C. Soeiro, Trypanosoma cruzi: alpha-2-macroglobulin regulates host cell apoptosis induced by the parasite infection in vitro. Experimental Parasitology. ,vol. 118, pp. 331- 337 ,(2008) , 10.1016/J.EXPPARA.2007.09.004