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Reductive Depolymerization of Bovine Thyroglobulin Multimers via Enzymatic Reduction of Protein Disulfide and Glutathiony­lated Mixed Disulfide Linkages  

Liu Xi-Wen (College of Pharmacy, Chungnam National University)
Sok Dai-Eun (College of Pharmacy, Chungnam National University)
Publication Information
Archives of Pharmacal Research / v.28, no.9, 2005 , pp. 1065-1072 More about this Journal
Abstract
The nascent thyroglobulin (Tg) multimer molecule, which is generated during the initial fate of Tg in ER, undergoes the rapid reductive depolymerization. In an attempt to determine the depolymerization process, various types of Tg multimers, which were generated from deoxy­cholate-treated/reduced Tg, partially unfolded Tg or partially unfolded/reduced Tg, were subjected to various GSH (reduced glutathione) reducing systems using protein disulfide isomerase (PDI), glutathione reductase (GR), glutaredoxin or thioredoxin reductase. The Tg multimers generated from deoxycholate-treated/reduced Tg were depolymerized readily by the PDI/GSH system, which is consistent with the reductase activity of PDI. The PDI/GSH-induced depolymerization of the Tg multimers, which were generated from either partially unfolded Tg or partially unfolded/reduced Tg, required the simultaneous inclusion of glutathione reductase, which is capable of reducing glutathionylated mixed disulfide (PSSG). This suggests that PSSG was generated during the Tg multimerization stage or its depolymerization stage. In particular, the thioredoxin/thioredoxin reductase system or glutaredoxin system was also effective in depolymerizing the Tg multimers generated from the unfolded Tg. Overall, under the net GSH condition, the depolymerization of Tg multimers might be mediated by PDI, which is assisted by other reductive enzymes, and the mechanism for depolymerizing the Tg multimers differs according to the type of Tg multimer containing different degrees and types of disulfide linkages.
Keywords
Depolymerization; Thyroglobulin (Tg); Protein disulfide isomerase (PDI); Reductase; Glutathione; Thiol-disulfide exchange;
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1 Bradford, M. M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248-254 (1976)   DOI   PUBMED   ScienceOn
2 Gentile, F., Pasquale, F., Mamone, G., Malorni, A., and Salvatore, G., Identification of Hormonogenic Tyrosines in Fragment 1218-1591 of Bovine Thyroglobulin by Mass Spectrometry. Hormonogenic acceptor Tyr-1291 and donor Tyr-1375. J. Biol. Chem., 272, 639-646 (1997)   DOI   ScienceOn
3 Herzog, V., Berndorfer, U., and Saber, Y., Isolation of insoluble secretory product from bovine thyroid: Extracellular storage of thyroglobulin in covalently cross-linked form. J. Cell Biol., 118,1071-1083 (1992)   DOI   ScienceOn
4 Laemmli, U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T 4. Nature, 227, 680-685 (1970)   DOI   PUBMED   ScienceOn
5 Malthiery, Y. and Lissitzky, S., Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA. Eur. J. Biochem., 165, 491-498 (1987)   DOI   ScienceOn
6 Tachibana, C. and Stevens, T. H., The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase. Mol. Cell. Biol., 12, 4601-4611 (1992)   DOI
7 Chernoff, S. B. and Rawitch, A. B., Thyroglobulin structurefunction. Isolation and characterization of a thyroxinecontaining polypeptide from bovine thyroglobulin. J. Biol. Chem., 256, 9425-9430 (1981)
8 LundstrOm-Ljung, J., Vlamis-Gardikas, A., Aslund, F., and Holmgren, A., Reactivity of glutaredoxins 1, 2, and 3 from Escherichia coli and protein disulfide isomerase towards glutathionyl-mixed disulfides in ribonuclease A. FEBS Lett., 443, 85-88 (1999)   DOI   ScienceOn
9 Freedman, R. B., Hirst, T. R., and Tuite, M. F., Protein disulphide isomerase: Building bridges in protein folding. Trends Biochem. Sci., 19,331-336 (1994)   DOI   PUBMED   ScienceOn
10 Kim, P. S. and Arvan, P., Folding and assembly of newly synthesized thyroglobulin occurs in a pre-Golgi compartment. J. Biol. Chem., 266, 12412-12418 (1991)
11 Holmgren, A., Thioredoxin and glutaredoxin systems. J. Biol. Chem., 264, 13963-13966 (1989)
12 Pagani, M., Fabbri, M., Benedetti, C., Fassio, A., Pilati, S., Bulleid, N. J., Cabibbo, A., and Sitia, R., Endoplasmic Reticulum Oxidoreductin 1-L$\beta$ (ERO1-L$\beta$), a Human Gene Induced in the Course of the Unfolded Protein Response. J. Biol. Chem., 275, 23685-23692 (2000)   DOI   ScienceOn
13 Ellman, G. L., Tissue sulfhydryl groups. Arch. Biochem. Biophys., 82, 70-77 (1959)   DOI   PUBMED   ScienceOn
14 Freedman, R. B., Bulleeid, N. J., Hawkins, H. C., and Paver, J. L., Role of protein disulphide-isomerase in the expression of native proteins, Biochem. Soc. Symp., 55, 167-192 (1989)
15 Kumari, K., Khanna, P., Ansari, N. H., and Srivastava, S. K., High-performance liquid chromatography method for the determination of protein-glutathione mixed disulfide. Anal. Biochem., 220, 374-376 (1994)   DOI   ScienceOn
16 Muresan, Z. and Arvan, P., Enhanced binding to the molecular chaperone BiP slows thyroglobulin export from the endoplasmic reticulum. Mol. Endocrinol., 12, 458-467 (1998)   DOI   ScienceOn
17 LundstrOm-Ljung, J., Birnbach, U., Rupp, K., Soling, H. D., and Holmgren, A., Two resident ER-protein, CaBP1 and CaBP2, with thioredoxin domains, are substrates for thioredoxin reductase: Comparison with protein disulfide isomerase. FEBS Lett., 357, 305-308 (1995)   DOI   ScienceOn
18 Beer, S. M., Taylor, E. R., Brown, S. E., Dahm, C. C., Costa, N. J,, Runswick, M. J., and Murphy, M. P., Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: Implications for mitochondrial redox regulation and antioxidant. J. Biol. Chem., 279, 47939-47951 (2004)   DOI   ScienceOn
19 Kuznetsov, G., Chen, L. B., and Nigam, S. K., Several endoplasmic reticulum stress proteins, including Erp72, interact with thyroglobulin during its maturation. J. Biol. Chem., 269, 22990-22995 (1994)
20 Tu, B. P., Ho-Schleyer, S. C., Travers, K. J., and Weissman, J. S., Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science, 290, 1571-1574 (2000)   DOI   PUBMED   ScienceOn
21 Debarbieux, L. and Beckwith, J., Electron avenue: Pathways of disulfide bond formation and isomerization. Cell, 99,117-119 (1999)   DOI   ScienceOn
22 Freedman, R. B., Hawkins, H. C., and McLaughlin, S. H., Protein disulfide-isomerase. Methods Enzymol., 251, 397-406 (1995)   DOI   PUBMED
23 Stehr, M., Schneider, G., Aslund, F., Holmgren, A., and Lindqvist, Y., Structural basis for the thioredoxin-like activity profile of the glutaredoxin-like NrdH-redoxin from Escherichia coli. J Biol. Chem., 276, 35836-35841 (2001)   DOI   ScienceOn
24 Gravina, S. A. and Mieyal, J. J., Thioltransferase is a specific glutathionyl mixed disulfide oxidoreductase. Biochemistry, 32, 3368-3376 (1993)   DOI   ScienceOn
25 Berardi, M. J. and Bushweller, J. H., Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction. J. Mol. Biol., 292, 151-161 (1999)   DOI   ScienceOn
26 Gentile, F., Di Lauro, R., and Salvatore, G., in Endocrinology, In DeGroot, L. J., 3rd Ed., pp. 517-542, W. B. Saunders Co., Philadelphia, PA (1995)
27 Kim, P. S. and Arvan, P,, Calnexin and BiP act as sequential molecular chaperones during thyroglobulin folding in the endoplasmic reticulum. J. Cell Biol., 128, 29-38 (1995)   DOI   ScienceOn
28 Kim, P. S., Kwon, O. Y., and Arvan, P., An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism. J. Cell Biol., 133, 517-527 (1996)   DOI   ScienceOn
29 Hayanod, T., Inakaa, K., Otsu, M., Taniyama, Y., Mikib, K., Matsushima, M., and Kikuchi, M., PDI and glutathionemediated reduction of the glutathionylated variant of human lysozyme. FEBS Lett., 328, 203-208 (1993)   DOI   PUBMED   ScienceOn
30 Kim, P. S., Kim, K.-R., and Arvan, P, Disulfide-linked aggregation of thyroglobulin normally occurs during nascent protein folding. Am. J. Physiol. Cell Physiol., 265, C704-C711 (1993)   DOI
31 Gething, M. J. and Sambrook, J., Transport and assembly processes in the endoplasmic reticulum. Semin. Cell Biol., 1, 65-72 (1990)
32 Jung, C. H. and Thomas, J. A., S-Glutathiolated hepatocyte proteins and insulin disulfides as substrates for reduction by glutaredoxin, thioredoxin, protein disulfide isomerase, and glutathione. Arch. Biochem. Biophys., 335, 61-72 (1996)   DOI   ScienceOn
33 Mercken, L., Simons, M.-J., Swillens, S., Massaer, M., and Vassart, G., Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Nature, 316, 647-651 (1985)   DOI   ScienceOn
34 Rietsch, A., Bessette, P., Georgiou, G., and Beckwith, J., Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin. J. Bacteriol., 179, 6602-6608 (1997)   DOI
35 Casagrande, S., Bonetto, V., Fratelli, M., Gianazza, E., Eberini, I., Massignan, T., Salmona, M., Chang, G., Holmgren, A., and Ghezzi, P., Glutathionylation of human thioredoxin: a possible crosstalk between the glutathione and thioredoxin systems. Proc. Natl. Acad. Sci. U.S.A., 99, 9617-9618 (2002)   DOI   ScienceOn
36 Freedman, R. B., Trends Biochem. Sci., 9, 438-441 (1984)   DOI   ScienceOn
37 Wang, Q. and Chang, A., Eps1, a novel PDI-related protein involved in ER quality control in yeast. EMBO J., 18, 5972-5982 (1999)   DOI   ScienceOn
38 Kim, P. S., Bole, D., and Arvan, P., Transient aggregation of nascent thyroglobulin in the endoplasmic reticulum: Relationship to the molecular chaperone, BiP J. Cell. Biol., 118, 541-549 (1992)   DOI   ScienceOn