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Differences in the Plasma Proteome of Patients with Hypothyroidism before and after Thyroid Hormone Replacement: A Proteomic Analysis
- Source :
- International Journal of Molecular Sciences; Volume 19; Issue 1; Pages: 88, International Journal of Molecular Sciences
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- Thyroid hormone is a potent stimulator of metabolism, playing a critical role in regulating energy expenditure and in key physiological mechanisms, such as growth and development. Although administration of thyroid hormone in the form of levo thyroxine (l-thyroxine) has been used to treat hypothyroidism for many years, the precise molecular basis of its physiological actions remains uncertain. Our objective was to define the changes in circulating protein levels that characterize alterations in thyroid hormone status. To do this, an integrated untargeted proteomic approach with network analysis was used. This study included 10 age-matched subjects with newly diagnosed overt hypothyroidism. Blood was collected from subjects at baseline and at intervals post-treatment with l-thyroxine until they reached to euthyroid levels. Plasma protein levels were compared by two-dimensional difference in gel electrophoresis (2D-DIGE) pre- and post-treatment. Twenty differentially expressed protein spots were detected. Thirteen were identified, and were found to be unique protein sequences by MALDI-TOF mass spectrometry. Ten proteins were more abundant in the hypothyroid vs. euthyroid state: complement C2, serotransferrin, complement C3, Ig κ chain C region, α-1-antichymotrypsin, complement C4-A, haptoglobin, fibrinogen α chain, apolipoprotein A-I, and Ig α-1 chain C region. Three proteins were decreased in abundance in the hypothyroid vs. euthyroid state: complement factor H, paraneoplastic antigen-like protein 6A, and α-2-macroglobulin. The differentially abundant proteins were investigated by Ingenuity Pathway Analysis (IPA) to reveal their associations with known biological functions. Their connectivity map included interleukin-6 (IL-6) and tumour necrosis factor α (TNF-α) as central nodes and the pathway identified with the highest score was involved in neurological disease, psychological disorders, and cellular movement. The comparison of the plasma proteome between the hypothyroid vs euthyroid states revealed differences in the abundance of proteins involved in regulating the acute phase response.
- Subjects :
- Male
0301 basic medicine
Proteome
endocrine system diseases
0302 clinical medicine
Gene Regulatory Networks
Euthyroid
Protein Interaction Maps
Spectroscopy
Complement component 2
l-thyroxine
Thyroid
Transferrin
Acute-phase protein
Complement C3
General Medicine
Middle Aged
Blood proteins
Computer Science Applications
medicine.anatomical_structure
Complement Factor H
Factor H
acute phase proteins
Female
Adult
medicine.medical_specialty
Hormone Replacement Therapy
030209 endocrinology & metabolism
Biology
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
proteomics
Hypothyroidism
Internal medicine
medicine
Humans
alpha-Macroglobulins
Physical and Theoretical Chemistry
Molecular Biology
Interleukin-6
Tumor Necrosis Factor-alpha
Organic Chemistry
Fibrinogen
Apolipoproteins
030104 developmental biology
Endocrinology
hypothyroidism
l-thyroxine%22">">l-thyroxine
inflammation
Hormone
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....04c908f43928dadcf5e1edbe2909c5d3
- Full Text :
- https://doi.org/10.3390/ijms19010088