Proteomics Profiling of the Urine of Patients with Hyperthyroidism after Anti-Thyroid Treatment

Abstract

Hyperthyroidism, which is characterized by increased circulating thyroid hormone levels, alters the body’s metabolic and systemic hemodynamic balance and directly influences renal function. In this study, the urinary proteome of patients with hyperthyroidism was characterized using an untargeted proteomic approach with network analysis. Urine samples were collected from nine age-matched patients before and after carbimazole treatment. Differences in the abundance of urinary proteins between hyperthyroid and euthyroid states were determined using a 2D-DIGE coupled to MALDI-TOF mass spectrometry. Alterations in the abundance of urinary proteins, analyzed via Progenesis software, revealed a statistically significant difference in abundance in a total of 40 spots corresponding to 32 proteins, 25 up and 7 down (≥1.5-fold change, ANOVA, p ≤ 0.05). The proteins identified in the study are known to regulate processes associated with cellular metabolism, transport, and acute phase response. The notable upregulated urinary proteins were serotransferrin, transthyretin, serum albumin, ceruloplasmin, alpha-1B-glycoprotein, syntenin-1, and glutaminyl peptide cyclotransferase, whereas the three notable downregulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase, and serpin B3 (SERPINB3). Bioinformatic analysis using ingenuity pathway analysis (IPA) identified the dysregulation of pathways associated with cellular compromise, inflammatory response, cellular assembly, and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes.

Urinary Proteomic Signature in Acute Decompensated Heart Failure: Advances into Molecular Pathophysiology

“…TTR triggers amyloid processes, and TTR amyloid cardiomyopathy is increasingly being recognized in the clinical setting as a possible heart failure origin [41]. Additionally, TTR, along with serotransferrin (TF), is involved in the acute inflammatory response in increased chronic inflammation [9]. More importantly, TTR is a crucial protein involved in the transport of retinol to peripheral tissues after forming a homotetramer complex with the retinol-specific carrier RBP4.…”

“…Sixteen proteins were identified by MS/MS working on the lift mode after peptide fragmentation of the three monoisotopic peaks with higher intensity (Table 1 with additional information in Supplementary Table S3). Selected peptides had a median length of 11 (9)(10)(11)(12)(13)(14) amino acids. Seven peptides presented a cysteine (C) carbamidomethylation and one peptide had a methionine (M) oxidation; both types of modifications were taken into account for the fragment mass analysis and MASCOT MS/MS ion search.…”

“…Differential proteome signatures between normal and disease states can be determined by using targeted and untargeted mass spectrometry (MS)-based proteomic approaches [9,10]. MS analysis has emerged as a powerful tool in proteomics to identify and characterize proteins and protein complexes in biological samples including blood, urine, tissues, and cells.…”

Comparative Proteomic Analysis to Investigate the Pathogenesis of Oral Adenoid Cystic Carcinoma

“…As stated in previous studies, MS-based proteomics should strive to maintain accuracy within a range of 1.3- to 2-folds. Then, we chose the 1.5-fold change as an acceptable threshold of the statistically significant difference. − …”