Dataset Information

Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach.

ABSTRACT: 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.

SUBMITTER: Masood A

PROVIDER: S-EPMC7841925 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach.

Masood Afshan A Benabdelkamel Hicham H Jammah Anwar A AA Ekhzaimy Aishah A AA Alfadda Assim A AA

ACS omega 20210113 3

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 proteo ...[more]

PMID: 33521475

Similar Datasets

Project description:BackgroundThe cornea is a specialized transparent connective tissue responsible for the majority of light refraction and image focus for the retina. There are three main layers of the cornea: the epithelium that is exposed and acts as a protective barrier for the eye, the center stroma consisting of parallel collagen fibrils that refract light, and the endothelium that is responsible for hydration of the cornea from the aqueous humor. Normal cornea is an immunologically privileged tissue devoid of blood vessels, but injury can produce a loss of these conditions causing invasion of other processes that degrade the homeostatic properties resulting in a decrease in the amount of light refracted onto the retina. Determining a measure and drift of phenotypic cornea state from normal to an injured or diseased state requires knowledge of the existing protein signature within the tissue. In the study of corneal proteins, proteomics procedures have typically involved the pulverization of the entire cornea prior to analysis. Separation of the epithelium and endothelium from the core stroma and performing separate shotgun proteomics using liquid chromatography/mass spectrometry results in identification of many more proteins than previously employed methods using complete pulverized cornea.ResultsRabbit corneas were purchased, the epithelium and endothelium regions were removed, proteins processed and separately analyzed using liquid chromatography/mass spectrometry. Proteins identified from separate layers were compared against results from complete corneal samples. Protein digests were separated using a six hour liquid chromatographic gradient and ion-trap mass spectrometry used for detection of eluted peptide fractions. The SEQUEST database search results were filtered to allow only proteins with match probabilities of equal or better than 10-3 and peptides with a probability of 10-2 or less with at least two unique peptides isolated within the run along with default Xcorr values. These parameters resulted in the identification of over 350 proteins, including over 225 new proteins not previously detected in the cornea by mass spectrometry. In addition, corneal layer separation resulted in identification of nearly every protein that was identified in the complete cornea assay. The epithelium and endothelium each revealed many unique proteomes specific to each layer. In the endothelium, the protein olfactomedin-like 3 was identified for the first time in the cornea by this analysis. Olfactomedin-3 is a neuronal expressed protein also known as optimedin that stimulates formation of cell adherent and cell-cell tight junctions and its expression modulates cytoskeleton organization and cell migration. However, the function of this protein in rabbit corneal endothelium is currently unknown.ConclusionThis manuscript presents a description of a more comprehensive proteomic profile for mammalian cornea compared to past methods. The use of simple dissection procedures of the tissue and the application of long chromatographic gradients, many more proteins can be identified.

Project description:ObjectiveEvidence indicates that L-T4 in liquid and softgel capsule are absorbed better than tablets in hypothyroid patients, even when patients are under medications that impair the intestinal absorption of L-T4. However, no study has evaluated all three L-T4 formulations in the same hypothyroid patients. This study aims to fill this gap. The outcome was the degree of TSH change in the liquid and softgel formulations, using tablet L-T4 as the reference, regardless of sequence of formulation and regardless of whether patients were co-ingesting with interfering medications.MethodsWe recorded serum TSH levels in two groups of L-T4 replaced patients with primary hypothyroidism (23 subjects who did not co-ingest interfering medications, and 20 subjects who did). Either group of patients took one formulation of L-T4 at a time with variable sequences. In the first group, the median durations of exposure to tablet, liquid or softgel L-T4 were 14, 9 and 10?months, respectively. In the second group the corresponding durations were 13, 11 and 10?months, during which patients co-ingested interfering medications.ResultsIn the 23 patients, there were 78, 74 or 101 TSH determinations during liquid, softgel capsule or tablet L-T4 regimens. Serum TSH levels associated with liquid, capsule or tablet L-T4 were 1.62?±?0.51, 1.77?±?0.44?mU/L (P?=?0.049 vs liquid) or 2.38?±?0.69?mU/L (P?<?0.0001 vs liquid or capsule). Rates of TSH???2.50?mU/L were 97.4% (liquid), 95.9% (softgel) or 64.4% (tablet, P?<?0.0001 vs liquid or capsule). Rates of TSH???4.12?mU/L were 100%, 100% or 98.0%.In the 20 patients, the corresponding TSH determinations were 56, 57 and 41, and corresponding TSH levels were 2.74?±?0.98, 2.70?±?0.79 or 7.53?±?2.82?mU/L. Rates of TSH???2.50?mU/L were 51.8% (liquid), 47.4% (capsule, P?=?0.64) or 2.4% (tablet, P?<?0.0001 vs liquid or capsule). Rates of TSH???4.12?mU/L were 92.8% (liquid), 94.7% (capsule, P?=?0.68) or 12.2% (tablet, P?<?0.0001 vs liquid or capsule).ConclusionsL-T4 ingested as liquid solution or softgel capsule is more bioavailable compared to L-T4 ingested as tablet, and it is slightly superior to capsule L-T4 only in the absence of co-ingestion of interfering medications.

Dataset Information

Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach.

Publications

Identification of Protein Changes in the Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets