Tissue transglutaminase

An alternative to modifying the functional group attached to fibrils is to utilise the chemistry present in the amino acid side chains. Furthermore, as peptides often undergo specific modification by enzymes in vivo, these could be harnessed for synthetic purposes. Qll (Ac-QQKFQFQFEQQ-Am, a fibril-forming peptide based on Pi 1-2), was coupled to lysine-based molecules by treatment with an enzyme (tissue transglutaminase, TGase) which results in a reaction between lysine and glutamine side chains [72] (Fig. 32). 

Murthy, S.N.P., Wilson, J., Guy, S.L. and Lorand, L. (1991) Intramolecular cross-linking of monomeric fibrinogen by tissue transglutaminase. Proceedings of the National Academy of Sciences USA 88, 10601-10604. 

Cheung W, Darfler M, Alvarez H, et al. Apphcation of a global proteomic approach to archival precursor lesions deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancers. Pancreatology 2008 8 608-616. 

An old hypothesis is based on the observations of Dahlen et al. (D3), who demonstrated that above a certain concentration in plasma, Lp(a) could bind to glycosaminoglycans in the arterial wall (B12). Colocalization of Lp(a) and fibrin on the arterial wall can lead to oxidative changes in the lipid moiety of Lp(a) and induce the formation of oxidatively modified cholesterol esters, which in turn can influence the interaction of Lp(a) and its receptors on macrophages. This process is promoted by the presence of calcium ions. Cushing (C14), Loscalzo (L22), and Rath (R3) reported a colocalization of undegraded Lp(a) and apo-Bl00 in the extracellular space of the arterial wall. In contrast to LDL, Lp(a) is a substrate for tissue transglutaminase and Factor XUIa and can be altered to products that readily interact with cell surface structures (B21). 

Mishra S, Saleh A, Espino PS, Davie JR, Murphy LJ (2006) Phosphorylation of histones by tissue transglutaminase. J Biol Chem 281 5532-5538... 

It appears that the a-synuclein contains intramolecular cross-links possibly mediated by tissue transglutaminase (Andringa et al., 2004 Muma, 2007 Ruan and Johnson, 2007). As noted above there is a theoretical possibility that carnosine may be a competitive inhibitor for tissue transglutaminase which could prevent formation of the a-synuclein crosslinks which may prevent Lewy body formation and proteasome inhibition. 

Junn, E., Ronchetti, R. D., Quezado, M. M., Kim, S. Y., and Mouradian, M. M. (2003). Tissue transglutaminase-induced aggregation of alpha-synuclein Implications for Lewy body formation in Parkinson s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA 100, 2047-2052. 

Abs, Antibodies CD, celiac disease DH, dermatitis herpetiformis Dx, Diagnosis EM, endomysial antibodies GI, gastrointestinal GFD, gluten-free diet IELs, intraepithelial lymphocytes IFN, interferon Lab, laboratory tTG, tissue transglutaminase antibodies Ret, reticulin IH, immunohistochemistry. 

Piper, J. L., Gray, G. M., and Khosla, C. (2002). High selectivity of human tissue transglutaminase for immunoactive gliadin peptides Implications for celiac sprue. Biochemistry 41, 386-393. 

Arentz-Hansen, H., Korner, R., Molberg, O. et al. 2000. The intestinal T cell response to a-gliadyn in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med 191 603-612. 

Hill, P. G. and Me Millan, S. A. 2006. Anti-tissue transglutaminase antibodies and their role in the investigation of coeliac disease. Ann Clin Biochem. 43 105-117. 

Collier, J.H., and Messersmith, P.B. "Enzymatic modification of self-assembled peptide structures with tissue transglutaminase". Bioconjugate Chem. 14(4), 748-755 (2003). 

Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997 3 797-801. 

Uhlig H, Osman AA, Tanev ID, Viehweg J, Mothes T. Role of tissue transglutaminase in gliadin binding to reticular extracellular matrix and relation to coeliac disease autoantibodies. Autoimmunity 1998 28 185-195. 

Sollid LM, Molberg O, McAdam S, Lundin KE. Autoantibodies in coeliac disease Tissue transglutaminase—guilt by association Gut 1997 41 851-852. 

Molberg O, Mcadam SN, Korner R, Quarsten H, Kristiansen C, Madsen L, et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by Gut-derived T cells in celiac disease. Nat Med 1998 4 713-717. Erratum in Nat Med 1998 4 974. 

Quarsten H, Molberg O, Fugger L, McAdam SN, Sollid LM. HLA binding and T cell recognition of a tissue transglutaminase-modified gliadin epitope. Eur J Immunol 1999 29 2506-2514. 

Schrodl D, Kahlenberg F, Zimmer K-P, Hermann W, Kuhn H-J, Mothes T. Intrathecal synthesis of autoantibodies against tissue transglutaminase. J Autoimmun 2004 22 335-340. 

Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, Gillett H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998 115 1317-1321. 

Sulkanen S, Halttunen T, Laurila K, Kolho KL, Korponay-Szabo IR, Samesto A, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998 115 1322-1328. 

Amin M, Eckhardt T, Kapitza S, Fleckenstein B, Jung G, Seissler J, et al. Correlation between tissue transglutaminase antibodies and endomysium antibodies as diagnostic markers of coeliac disease. Clin Chim Acta 1999 82 219-225. 

Sardy M, Odenthal U, Karpati S, Paulsson M, Smyth N. Recombinant human tissue transglutaminase ELISA for the diagnosis of gluten-sensitive enteropathy. Clin Chem 1999 45 2142-2149. 

Seissler J, Boms S, Wohlrab U, Morgenthaler NG, Mothes T, Boehm BO, et al. Antibodies to human recombinant tissue transglutaminase measured by radioligand assay Evidence for high diagnostic sensitivity for celiac disease. Horm Metab Res 1999 31 375-379. 

Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A, et al. Human recombinant tissue transglutaminase ELISA An innovative diagnostic assay for celiac disease. Am J Gastroenterol 2000 95 1253-1257. 

Osman AA, Richter T, Stern M, Conrad K, Henker J, Brandsch C, et al. Production of recombinant human tissue transglutaminase using baculovirus expression system and its application for serologic diagnosis of coeliac disease. Eur J Gastroenterol Hepatol 2002 14 1217-1223. 

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