scholarly journals Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study

2015 ◽  
Vol 4 (Suppl. 1) ◽  
pp. 119-124 ◽  
Author(s):  
Beatrice Engelmann ◽  
Julia Bischof ◽  
Anne-Luise Dirk ◽  
Nele Friedrich ◽  
Elke Hammer ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Blood Coagulation ◽  
Plasma Proteins ◽  
Pearson Correlation ◽  
Shotgun Proteomics ◽  
Coagulation Cascade ◽  
Label Free ◽  
Experimental Thyrotoxicosis ◽  
Protein Levels ◽  
Wide Variability

Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT4 levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT4, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.

Effect of experimental thyrotoxicosis onto blood coagulation – A proteomics study

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
B Engelmann ◽  
J Bischof ◽  
AL Dirk ◽  
N Friedrich ◽  
E Hammer ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Experimental Thyrotoxicosis ◽  
Proteomics Study

Differential Drug Target Selection in Blood Coagulation: What can we get from Computational Systems Biology Models?

2020 ◽  
Vol 26 (18) ◽  
pp. 2109-2115 ◽  
Author(s):  
Mikhail A. Panteleev ◽  
Anna A. Andreeva ◽  
Alexey I. Lobanov
Keyword(s):  
Blood Coagulation ◽  
Biological Network ◽  
Target Selection ◽  
Anticoagulation Therapy ◽  
Differential Regulation ◽  
Coagulation Cascade ◽  
Computational Systems Biology ◽  
Analysis Strategies ◽  
Optimal Target ◽  
Computational Systems

Discovery and selection of the potential targets are some of the important issues in pharmacology. Even when all the reactions and the proteins in a biological network are known, how does one choose the optimal target? Here, we review and discuss the application of the computational methods to address this problem using the blood coagulation cascade as an example. The problem of correct antithrombotic targeting is critical for this system because, although several anticoagulants are currently available, all of them are associated with bleeding risks. The advantages and the drawbacks of different sensitivity analysis strategies are considered, focusing on the approaches that emphasize: 1) the functional modularity and the multi-tasking nature of this biological network; and 2) the need to normalize hemostasis during the anticoagulation therapy rather than completely suppress it. To illustrate this effect, we show the possibility of the differential regulation of lag time and endogenous thrombin potential in the thrombin generation. These methods allow to identify the elements in the blood coagulation cascade that may serve as the targets for the differential regulation of this system.

Transcriptome profiling reveals the endogenous sponging role of LINC00659 and UST-AS1 in high altitude induced thrombosis

2021 ◽  
Author(s):  
Prabhash Kumar Jha ◽  
Aatira Vijay ◽  
Amit Prabhakar ◽  
Tathagata Chatterjee ◽  
Velu Nair ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
High Altitude ◽  
Expression Profile ◽  
Thrombus Formation ◽  
Pearson Correlation ◽  
Coagulation Cascade ◽  
Protein Coding ◽  
Vein Thrombosis ◽  
Protein Coding Genes ◽  
Deep Vein

Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. A little is known about the expression profile and roles of lncRNAs in human subjects developing DVT at high altitude. Methods: Using RNAseq, we compared peripheral blood mRNA and lncRNA expression profile in human High Altitude deep Vein Thrombosis (HA-DVT) patients with high altitude control subjects. We used DESeq to identify differentially expressed (DE) genes. We annotated the long noncoding RNAs using NONCODE 3.0 database. In silico putative lncRNA-miRNA association study unravels the endogenous miRNA sponge associated with our candidate lncRNAs. These findings were validated by siRNA knockdown assay of the candidate lncRNAs conducted in primary endothelial cells. Results: We identified 1524 DE mRNA and 973 DE lncRNAs. Co-expressed protein-coding genes analysis resulted in a list of 722 coexpressed protein-coding genes with a Pearson correlation coefficients >0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response and coagulation cascade. Through its miRNA response elements (MREs) to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulates the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. Conclusions: This transcriptome profile describes novel potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as biomarker in HA-DVT.

scholarly journals Analysis of the Barley Malt Rootlet Proteome

2019 ◽  
Vol 21 (1) ◽  
pp. 179 ◽  
Author(s):  
Ramamurthy Mahalingam
Keyword(s):  
Animal Feed ◽  
Protein Biosynthesis ◽  
In Silico Analysis ◽  
Shotgun Proteomics ◽  
Label Free ◽  
High Coverage ◽  
Barley Malt ◽  
Naturally Occurring ◽  
Two Stages ◽  
Silico Analysis

Barley seeds are one of the main ingredients of the malting industry for brewing beer. The barley rootlets that are separated from the kilned seeds at the end of the malting process and used as animal feed are one of the byproducts of this industry. In this study, the proteome of rootlets derived from two stages of the malting process, germination and kilning, from a popular malting barley variety were analyzed. A label-free shotgun proteomics strategy was used to identify more than 800 proteins from the barley rootlets. A high coverage and high confidence Gene Ontology annotations of the barley genome was used to facilitate the functional annotation of the proteins that were identified in the rootlets. An analysis of these proteins using Kellogg Encyclopedia of Genes and Genomes (KEGG) and Plant Reactome databases indicated the enrichment of pathways associated with phytohormones, protein biosynthesis, secondary metabolism, and antioxidants. Increased levels of jasmonic acid and auxin in the rootlets further supported the in silico analysis. As a rich source of proteins and amino acids use of these by-products of the malting industry for animal feed is validated. This study also indicates rootlets as a potential source of naturally occurring phenylpropanoids and antioxidants that can be further exploited in the development of functional foods.

Thyroid hormone specifically regulates skeletal muscle Na(+)-K(+)-ATPase alpha 2- and beta 2-isoforms

1993 ◽  
Vol 265 (3) ◽  
pp. C680-C687 ◽  
Author(s):  
K. K. Azuma ◽  
C. B. Hensley ◽  
M. J. Tang ◽  
A. A. McDonough
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
State Level ◽  
Mrna Abundance ◽  
Northern Analysis ◽  
Protein Abundance ◽  
Constant Amount ◽  
Protein Levels ◽  
Subunit Expression ◽  
Beta 2

The purpose of this study was to determine the pattern of thyroid hormone (triiodothyronine, T3) regulation of the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) alpha- and beta-subunit expression in skeletal muscle, which expresses alpha 1-, alpha 2-, beta 1-, and beta 2-subunits, and compare it with that seen in kidney, which expresses only alpha 1 and beta 1. Three steady states were studied: hypothyroid, euthyroid, and hyperthyroid (hypothyroids injected daily with 1 microgram T3/g body wt for 2-16 days). Protein and mRNA abundance, determined by Western and Northern analysis, were normalized to a constant amount of homogenate protein and total RNA, respectively. In skeletal muscle, there was no change in alpha 1- or beta 1-mRNA or protein levels in the transition from hypothyroid to hyperthyroid. However, alpha 2 was highly regulated; mRNA reached a new steady-state level of fivefold over hypothyroid by 8 days of T3 treatment and protein abundance increased threefold. In addition, beta 2-mRNA and protein were detected in skeletal muscle and were also highly regulated by T3; beta 2-mRNA increased nearly fourfold over hypothyroid level, and beta 2-protein abundance increased over twofold. In kidney in the transition from hypothyroid to hyperthyroid, there were coordinate 1.6-fold increases in both alpha 1- and beta 1-mRNA abundance that predicted the observed changes in alpha 1- and beta 1-protein levels and Na(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 5-36 ◽  
Author(s):  
Katarina Davalieva ◽  
Momir Polenakovic
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Biomarker Discovery ◽  
Molecular Level ◽  
Specific Antigen ◽  
Shotgun Proteomics ◽  
Comparative Proteomics ◽  
Label Free ◽  
The Past ◽  
Proteomics Research

Abstract Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa.

Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels

2008 ◽  
Vol 294 (6) ◽  
pp. E1160-E1168 ◽  
Author(s):  
Elena Silvestri ◽  
Assunta Lombardi ◽  
Pieter de Lange ◽  
Luigi Schiavo ◽  
Antonia Lanni ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Total Protein ◽  
Protein Level ◽  
Monocarboxylate Transporter ◽  
Type I ◽  
Peripheral Tissues ◽  
Protein Levels ◽  
Age Related ◽  
Liver And Kidney ◽  
Age Related Changes

Aging is associated with changes in thyroid gland physiology. Age-related changes in the contribution of peripheral tissues to thyroid hormone serum levels have yet to be systematically assessed. Here, we investigated age-related alterations in the contributions of the liver and kidney to thyroid hormone homeostasis using 6-, 12-, and 24-mo-old male Wistar rats. A significant and progressive decline in plasma thyroxine occurred with age, but triiodothyronine (T3) was decreased only at 24 mo. This was associated with an unchanged protein level of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the kidney and with a decreased MCT8 level in the liver at 24 mo. Hepatic type I deiodinase (D1) protein level and activity declined progressively with age. Renal D1 levels were decreased at both 12 and 24 mo but D1 activity was decreased only at 24 mo. In the liver, no changes occurred in thyroid hormone receptor (TR) TRα1, whereas a progressive increase in TRβ1 occurred at both mRNA and total protein levels. In the kidney, both TRα1 and TRβ1 mRNA and total protein levels were unchanged between 6 and 12 mo but increased at 24 mo. Interestingly, nuclear TRβ1 levels were decreased in both liver and kidney at 12 and 24 mo, whereas nuclear TRα1 levels were unchanged. Collectively, our data show differential age-related changes among hepatic and renal MCT8 and D1 and TR expressions, and they suggest that renal D1 activity is maintained with age to compensate for the decrease in hepatic T3 production.

Thyroid Hormone-Binding Plasma Proteins

1986 ◽  
pp. 97-101
Author(s):  
Georg Hennemann ◽  
Eric P. Krenning ◽  
Roelof Docter
Keyword(s):  
Thyroid Hormone ◽  
Plasma Proteins ◽  
Hormone Binding
Sign in / Sign up

Export Citation Format

Share Document