Involvement of Oxidative Reactions and Extracellular Protein Chaperones in the Rescue of Misassembled Thyroglobulin in the Follicular Lumen

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) a...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1999-02, Vol.255 (2), p.438-443
Main Authors: Delom, Frédéric, Lejeune, Pierre-Jean, Vinet, Liliane, Carayon, Pierre, Mallet, Bernard
Format: Article
Language:English
Subjects:
Carrier Proteins - isolation & purification
Chemical Fractionation
Extracellular Space - physiology
Goiter - metabolism
Goiter - pathology
Heat-Shock Proteins
HSP70 Heat-Shock Proteins - isolation & purification
Humans
Hydrolysis
Membrane Proteins - isolation & purification
Models, Biological
Molecular Chaperones - isolation & purification
Molecular Chaperones - physiology
Oxidation-Reduction
Polymers - chemistry
protein chaperones
Protein Disulfide-Isomerases - metabolism
Protein Folding
reactive oxygen species
Reactive Oxygen Species - physiology
Solubility
thyroglobulin
Thyroglobulin - chemistry
Thyroglobulin - metabolism
Thyroid Gland - metabolism
Thyroid Gland - pathology
Tyrosine - analogs & derivatives
Tyrosine - metabolism
unfolded proteins
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.0229