Transthyretin variant in Thai people is likely to associate with pathogenesis
Keywords:
Transthyretin, variant, amyloid fibril, cytotoxicityAbstract
In this research, we study a tendency to pathogenesis of a transthyretin variant (TTR variant) which was identified in Thai people. The cDNA of TTR variant was constructed from the cDNA of human TTR wild type (TTR WT) by Site-Directed Mutagenesis following by ligation into pPIC 3.5 expression vector and transformation into Pichia pastoris. The recombinant TTR variant was successfully synthesized by Pichia, and it was purified by preparative native-PAGE. In the comparison, TTR variant migrated on a non-denatured polyacrylamide gel faster than albumin in human plasma. Its molecular mass analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was approximately 17 kilodaltons. The ability to form fibril of TTR variant was investigated by Thioflavin T assay, and it showed that TTR variant definitely formed fibril under the physiological condition faster than L55P and TTR WT, indicating low stability of tetrameric structure of TTR variant. Cytotoxicity of the variant to human neuroblastoma cells (LAN-5) determined by MTT assay showed that TTR variant had higher toxicity than L55P. The results demonstrated a potential pathogenesis of the studied TTR variant.
References
Ahmad, M., Hirz, M., Pichler, H. and Schwab, H. 2014. Protein expression in Pichia pastoris: recent achivements and perspective for heterologous protein production. Applied Microbiology Biotechnology 98(12): 5301- 5317.
Ando, Y., Nakamura, M. and Araki, S. 2005. Transthyretin-related familial amyloidotic polyneuropathy. Archives of Neurology 62(7): 1057-1062.
Arsequell, G. and Planas, A. 2012. Methods to evaluate the inhibition of TTR fibrillogenesis induced by small ligands. Current Medical Chemistry 19(1): 1-13.
Babbes, A.R.H., Powers, E.T. and Kelly, J.W. 2008. Quantification of the thermodynamically linked quaternary and tertiary structural stabilities of transthyretin and its disease- associated variants-the relationship between stability and amyloidosis. Biochemistry 47(26): 6969-6984.
Balamurugan, V., Reddy, G.R. and Suryanarayana, V.V.S. 2007. Pichia pastoris: A notable heterologous expression system for the production of foreign proteins-vaccines. Indian Journal of Biotechnology 6: 175-180.
Carr, A.S., Pelayo-Negro, A.L., Jaunmuktane, Z., Scalco, R.S., Hutt, D., Evans, M.R., Heally, E., Brandner, S., Holton, J., Blake, J., Whelan, C.J., Wechlekar, A.D., Gillmore, J.D., Hawkins, P.N. and Reilly, M.M. 2015. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy. Neuromuscular Disorders 25(6): 511-515.
Cavallaro, T., Martone, R.L., Dwork, A.J., Schon, E.A. and Herbert, J. 1990. The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye. Investigative Ophthalmology and Visual Science 31(3): 497-501.
Cereghino, J.L. and Cregg, J.M. 2000. Heterologous protein expression in the methylotrophic yeast Pichia Pastoris. FEMS Microbiology Review 24(1): 45-66.
Duan, W., Richardson, S.J., Kohrle, J., Chang, L., Southwell, B.R., Harms, P.J., Brack, C.M., Petterson, T.M. and Schreiber, G. 1995. Binding of thyroxine to pig transthyretin, its cDNA structure, and other properties. European Journal of Biochemistry 230(3): 977-986.
Ferreira, P., Anna, O.S., Varejao, N., Lima, C., Novis, S., Barbosa, R.V., Caldeira, C.M., Rumjnek, F.D., Ventura, S., Cruz, M.W. and Foguel, D. 2013. Structure-based analysis of transthyretin involved in familial amyloid cardiomyopathy. Plos One 8(12): 1-14.
Groenning, M. 2010. Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status. Journal of Chemical Biology 3: 1-18.
Hou, X., Richardson, S.J., Aguilar, M.I. and Small, D.H. 2005. Binding of amyloidogenic transthyretin to the plasma membrane alters membrane fluidity and induces neurotoxicity. Biochemistry 44(34): 11618-11627.
Ikeda, S. 2004. Cardiac amyloidosis: Heterogenous pathogenic backgrounds. Internal Medicine 43(12): 1107-1114.
Jacobson, D.R., Pastore, R.D., Yaghoubian, R., Kane, I., Gallo, G., Buck, F.S. and Buxbaum, J.N. 1997. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. The New England Journal of Medicine 336(7): 466-473.
Jiang, X., Buxbaum, J.N. and Kelly, J.W. 2001. The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis. Proceedings of the National Academy of Sciences of the United States of America 98(26): 14943-14948.
Khurana, R., Coleman, C., Zanetti, C.I., Carter, S.A., Krishna, V., Grover, R.K., Roy, R. and Sing, S. 2005. Mechanism of thioflavin T binding to amyloid fibrils. Journal of Structure Biology 151: 229-238.
Kierdorf, K. and Fritz, G. 2013. RAGE regulation and signaling in inflammation and beyond. Journal of Leukocyte Biology 94: 55-68.
Lai, Z., Colon, W. and Kelly, J.W. 1996. The acid-mediated denaturation pathway of transthyrtin yields a conformational intermediate that can self-assemble into amyloid. Biochemistry 35: 6470-6848.
Lashuel, H.A., Wurth, C., Woo, L. and Kelly, J.W. 1999. The most pathogenic transthyretin variant, L55P, form amyloid fibrils under acidic conditions and protofilaments under physiological conditions. Biochemistry 38: 13560-13573.
Leelawatwattana, L., Praphanphoj, V. and Prapunpoj, P. 2011. Effect of the N-terminal sequence on the binding affinity of transyhyretin for human retinol-binding protein. FEBS Journal 278(18): 3337-3347.
Palha, J.A. 2002. Transthyretin as a thyroid hormone carrier: function revisited. Clinical Chemistry and Laboratory Medicine 40(12): 1292-1300.
Patrick, S.M., Fazenda, M.L., McNeil, B. and Harvey, L.M. 2005. Heterologous protein production using the Pichia pastoris expression system. Yeast 22: 249-270.
Prapunpoj, P., Leelawatwatana, L., Schreiber, G. and Richardson, S.J. 2006. Change in structure of the N-terminal region of transthyretin produces change in affinity of transthyretin to T4 and T3. FEBS Journal 273(17): 4013-4023.
Prapunpoj, P., Richardson, S.J. and Schreiber, G. 2002. Crocodile transthyretin: structure, function, and evolution. American Journal of Physiology Regulatory Integrative and Comparative Physiology 283(4): R885-R896.
Quintas, A., Sariava, M.J.M. and Brioto, R.M.M. 1997. The amyloidogenic potential of transthyretin variants correlates with their tendency to aggregate in solution. FEBS Letters 418(3): 297-300.
Quintas, A., Sariava, M.J.M. and Brioto, R.M.M. 1999. The tetrameric protein transthyretin dissociates to a non-native monomer in solution A NOVEL MODEL FOR AMYLOIDOGENESIS. Journal of Biological Chemistry 274(46): 32943-32949.
Quintas, A., Vaz, D.C., Cardoso, I., Sariava, M.J.M. and Brioto, R.M.M. 2001. Tetramer dissociation and monomer partial unfolding precedes protofibril formation in amyloidogenic transthyretin variants. Journal of Biological Chemistry 276(29): 27207-27213.
Reixach, N., Deechongkit, S., Jiang, X., Kelly, J.W. and Buxbaum, J.N. 2004. Tissue damage in the amyloidosis: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proceedings of the National Academy of Sciences of the United States of America 101(9): 2817-2822.
Sant’anna, R.O., Braga, C.A., Polikarpov, I., Ventura, S., Mauricio, L., Lima, T.R. and Foguel, D. 2013. Inhibition of human transthyretin aggregation by non-steriodal anti-inflamatory compounds: A structural and thermodynamic analysis. International Journal of Molecular Sciences 14(3): 5284-5311.
Schmidt, A.M., Yan, S.D., Yan, S.F. and Stern, D.M. 2000. The biology of the receptor for advance glycation end products and its ligands. Biochemica et Biophysica Acta 1498: 99-111.
Schreiber, G. 2002. The evolution of transthyretin synthesis in the choroid plexus. Clinical Chemistry and Laboratory Medicine 40(12): 1200-1210.
Sebastião, M.P., Saraiva, M.J. and Damas, A.M. 1998. The crystal structure of amyloidogenic Leu55Pro transthyretin variant reveals a possible pathway for transthyretin polymerization into amyloid fibrils. Journal of Biological Chemistry 273(38): 24715-24722.
Sousa, M.M., Fernandes, R., Palha, J.A., Taboada, A., Vieira, P. and Saraiva, M.J. 2002. Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro. The American Journal of Pathology 161(5): 1935-1948.
Sousa, M.M. and Saraiva, M.J. 2003. Neurodegeneration in familial amyloid polyneuropathy: from pathology to molecular signaling. Progress in Neurobiology 71(5): 385-400.
Sousa, M.M., Yan, S.D., Fernandes, R., Guimaraes, A., Stern, D. and Sariava, M.J. 2001. Familial amyloid polyneuropathy: receptor for advance glycation end products-dependent triggering of neuronal inflammatory and apoptotic pathway. The Journal of Neuroscience 21(19): 7576-7586.
Sousa, M.M., Yan, S.D., Stern, D. and Sariava, M.J. 2000. Interaction of the receptor for advanced glycation end product (RAGE) with transthyretin triggers nuclear transcription factor kB (NF-kB) activation. Laboratory Investigation 80(7): 1101-1110.
Terry, C., Damas, A.M., Oliveira, P., Saraiva, M.J., Alves, I., Costa, P., Sakaki, Y. and Blake, C. 1993. Structure of Met30 variant of transthyretin and its amyloidogenic implications. The EMBO Journal 12(2): 735-741.
Ueda, M. and Ando, Y. 2014. Recent advances transthyretin amyloidosis therapy. Translational Neurodegeneration 3(19): 1-10.
Westen, M.W.T., van der Bosch, T.J., Wind, R.D., Mooibroek, H. and de Wolf, F.A. 1999. High-yield secretion of recombinant gelatins by Pichia pastoris. Yeast 15(11): 1087-1096.
Xiang, Q., Bi, R., Xu, M., Zhang, D.F., Tan, L., Zhang, C., Fang, Y., Yao, Y.G. 2017. Rare genetic variants of the transthyretin gene and associated with Alzheimer’s disease in Han Chinese. Molecular Neurobiology 54(7): 5192-5200.
Yang, M., Lei, M. and Huo, S. 2003. Why is Leu55→Pro55 transthyretin variant the most amyloidogenic: Insight from molecular dinamics simulations of transthyretin monomers. Protein Science 12: 1222-1231.
Downloads
Published
How to Cite
Issue
Section
License
The content and information in the article published in Journal of Rajamangala University of Technology Srivijaya It is the opinion and responsibility of the author of the article. The editorial journals do not need to agree. Or share any responsibility.