Regular Article
Involvement of Oxidative Reactions and Extracellular Protein Chaperones in the Rescue of Misassembled Thyroglobulin in the Follicular Lumen,☆☆

https://doi.org/10.1006/bbrc.1999.0229Get rights and content

Abstract

Reactive oxygen species (ROS) are involved in many pathological processes through modifications of structure and activity of proteins. ROS also participate in physiological pathways such as thyroid hormone biosynthesis, which proceeds through oxidation of the prothyroid hormone (thyroglobulin, Tg) and iodide. Regarding the colloidal insoluble multimerized Tg (m-Tg), which bears dityrosine bridges and is present in the follicular lumen, a mild oxidative system generated different soluble forms of Tg, more or less compacted by hydrophobic associations, and linked with Grp78 and Grp94.In vitro,the combined action of ROS and PDI, in the presence of free glutathione (reduced/oxidized), increased the solubility of this misassembled Tg and partially restored the ability of Tg to synthesize hormones. Our results show that protein chaperones escape from the ER and are involved with ROS in thyroid hormone synthesis. Therefore, we propose a model of roles of m-Tg in the follicular lumen.

References (26)

  • K.J.A. Davies et al.

    J. Biol. Chem.

    (1987)
  • B.S. Berlett et al.

    J. Biol. Chem.

    (1997)
  • B. Mallet et al.

    J. Biol. Chem.

    (1995)
  • G. Kuznetsov et al.

    J. Biol. Chem.

    (1997)
  • R.B. Freedman

    Trends Biochem. Sci.

    (1984)
  • G. Kuznetsov et al.

    J. Biol. Chem.

    (1994)
  • C. Hammond et al.

    Curr. Opin. Cell. Biol.

    (1995)
  • N. Baudry et al.

    Biochem. Biophys. Res. Commun.

    (1998)
  • M.D. Jacobson

    Trends Biochem. Sci.

    (1996)
  • U. Bjorkman et al.

    Eur. J. Biochem.

    (1982)
  • M-J. Gething et al.

    Nature

    (1992)
  • T.P. Prim et al.

    J. Biol. Chem.

    (1996)
  • Cited by (25)

    • Extracellular AGR2 triggers lung tumour cell proliferation through repression of p21<sup>CIP1</sup>

      2021, Biochimica et Biophysica Acta - Molecular Cell Research
      Citation Excerpt :

      Similarly, other ER-resident PDI proteins are found secreted in the extracellular microenvironment. For example, we have shown that PDIA2 is secreted into the lumen of the thyroid follicles by thyrocytes to control extracellular thyroglobulin folding and multimerization [12,13]. It has been also reported that PDIA3 is secreted and interacts with extracellular matrix proteins [14] and that QSOX1 is secreted and participates in laminin assembly thereby controlling extracellular matrix functionality [15].

    • Zeolites are effective ROS-scavengers in vitro

      2011, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      Evidence has accumulated pointing to the involvement of free radicals, and reactive oxygen species (ROS) in particular, in damage to various components of the cell [1]. Although some ROS are involved in physiological processes [2–4], most are deleterious for humans. Numerous studies have demonstrated that hemodialysis is responsible for the formation of abundant ROS from phagocytic cells activated in contact with dialysis membranes [5,6].

    View all citing articles on Scopus

    Abbreviations used: ROS, reactive oxygen species; Grp, glucose regulated protein; ER, endoplasmic reticulum; PDI, protein disulfide isomerase; Tg, thyroglobulin; SDS–PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; DTT, dithiothreitol; TPO, thyroperoxidase; LPO, lactoperoxidase

    ☆☆

    Braverman, L. E.Utiger, R. D.

    1

    To whom correspondence and reprint requests should be addressed. Fax: (33) 4.91.79.77.74. E-mail:[email protected].

    View full text