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Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach
[Image: see text] The thyroid gland and thyroid hormones control a multitude of homeostatic functions including maintenance of fluid and electrolyte balance and normal functioning of the kidneys. Thyroid dysfunction alters the sytemic hemodynamic and metabolic balance, thereby affecting the kidney....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841925/ https://www.ncbi.nlm.nih.gov/pubmed/33521475 http://dx.doi.org/10.1021/acsomega.0c05686 |
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author | Masood, Afshan Benabdelkamel, Hicham Jammah, Anwar A. Ekhzaimy, Aishah A. Alfadda, Assim A. |
author_facet | Masood, Afshan Benabdelkamel, Hicham Jammah, Anwar A. Ekhzaimy, Aishah A. Alfadda, Assim A. |
author_sort | Masood, Afshan |
collection | PubMed |
description | [Image: see text] The thyroid gland and thyroid hormones control a multitude of homeostatic functions including maintenance of fluid and electrolyte balance and normal functioning of the kidneys. Thyroid dysfunction alters the sytemic hemodynamic and metabolic balance, thereby affecting the kidney. In this study, we aimed to identify and characterize the urinary proteome of the patients with hypothyroidism. An untargeted proteomic approach with network analysis was used to identify changes in total urinary proteome in patients with newly diagnosed overt hypothyroidism. Urine samples were collected from nine age-matched patients’ before and after l-thyroxine treatment. Differences in the abundance of urinary proteins between hypothyroid and euthyroid states were determined using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled to matrix-assisted laser desorption and ionization time-of-flight (MALDI TOF) mass spectrometry. Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 49 spots corresponding to 42 proteins, 28 up and 14 down (≥1.5-fold change, analysis of variance (ANOVA), p ≤ 0.05). The proteins identified in the study are known to regulate processes related to transport, acute phase response, oxidative stress, generation of reactive oxygen species, cellular proliferation, and endocytosis. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related to amino acid metabolism, molecular transport, and small-molecule biochemistry and involved the MAPK kinase, vascular endothelial growth factor (VEGF), PI3 kinase/Akt, protein kinase C (PKC), signaling pathways. The identified proteins were involved in the regulation of thyroglobulin (Tg) and thyrotropin (TSH) metabolism. Alterations in their levels indicate the presence of a compensatory mechanism aimed at increasing the regulation of Tg in the hypothyroid state. |
format | Online Article Text |
id | pubmed-7841925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-78419252021-01-29 Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach Masood, Afshan Benabdelkamel, Hicham Jammah, Anwar A. Ekhzaimy, Aishah A. Alfadda, Assim A. ACS Omega [Image: see text] The thyroid gland and thyroid hormones control a multitude of homeostatic functions including maintenance of fluid and electrolyte balance and normal functioning of the kidneys. Thyroid dysfunction alters the sytemic hemodynamic and metabolic balance, thereby affecting the kidney. In this study, we aimed to identify and characterize the urinary proteome of the patients with hypothyroidism. An untargeted proteomic approach with network analysis was used to identify changes in total urinary proteome in patients with newly diagnosed overt hypothyroidism. Urine samples were collected from nine age-matched patients’ before and after l-thyroxine treatment. Differences in the abundance of urinary proteins between hypothyroid and euthyroid states were determined using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled to matrix-assisted laser desorption and ionization time-of-flight (MALDI TOF) mass spectrometry. Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 49 spots corresponding to 42 proteins, 28 up and 14 down (≥1.5-fold change, analysis of variance (ANOVA), p ≤ 0.05). The proteins identified in the study are known to regulate processes related to transport, acute phase response, oxidative stress, generation of reactive oxygen species, cellular proliferation, and endocytosis. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related to amino acid metabolism, molecular transport, and small-molecule biochemistry and involved the MAPK kinase, vascular endothelial growth factor (VEGF), PI3 kinase/Akt, protein kinase C (PKC), signaling pathways. The identified proteins were involved in the regulation of thyroglobulin (Tg) and thyrotropin (TSH) metabolism. Alterations in their levels indicate the presence of a compensatory mechanism aimed at increasing the regulation of Tg in the hypothyroid state. American Chemical Society 2021-01-13 /pmc/articles/PMC7841925/ /pubmed/33521475 http://dx.doi.org/10.1021/acsomega.0c05686 Text en © 2021 The Authors. Published by American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Masood, Afshan Benabdelkamel, Hicham Jammah, Anwar A. Ekhzaimy, Aishah A. Alfadda, Assim A. Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach |
title | Identification of Protein Changes in the Urine of
Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach |
title_full | Identification of Protein Changes in the Urine of
Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach |
title_fullStr | Identification of Protein Changes in the Urine of
Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach |
title_full_unstemmed | Identification of Protein Changes in the Urine of
Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach |
title_short | Identification of Protein Changes in the Urine of
Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach |
title_sort | identification of protein changes in the urine of
hypothyroid patients treated with thyroxine using proteomics approach |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841925/ https://www.ncbi.nlm.nih.gov/pubmed/33521475 http://dx.doi.org/10.1021/acsomega.0c05686 |
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