Dataset Information

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure.

ABSTRACT: Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls, n = 30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change |??1.5|, p ? 0.05). Ingenuity pathway analysis of proteome datasets suggested that the pathways involved in phagocytes' migration, free radical production, and cell death were activated and fatty acid metabolism was decreased in HF subjects. Multivariate adaptive regression splines modeling of datasets identified a panel of proteins that will provide >90% prediction success in classifying HF subjects. Proteomic profiling identified ATP-synthase, thrombospondin-1 (THBS1), and vinculin (VCL) as top differentially abundant and S-NO-modified proteins, and these proteins were verified by Western blotting and ELISA in different set of HF subjects. We conclude that differential abundance and S-NO modification of proteins serve as a mechanism in regulating cell viability and free radical production, and THBS1 and VCL evaluation will potentially be useful in the prediction of heart failure.

SUBMITTER: Koo SJ

PROVIDER: S-EPMC5007369 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure.

Koo Sue-Jie SJ Spratt Heidi M HM Soman Kizhake V KV Stafford Susan S Gupta Shivali S Petersen John R JR Zago Maria P MP Kuyumcu-Martinez Muge N MN Brasier Allan R AR Wiktorowicz John E JE Garg Nisha Jain NJ

International journal of proteomics 20160818

Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls, n = 30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified ...[more]

PMID: 27635260

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Project description:Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy controls (N/H, n = 30) and subjects that were seropositive for Tc-specific antibodies, but were clinically asymptomatic (C/A, n = 25) or clinically symptomatic (C/S, n = 28) with cardiac involvement and left ventricular dysfunction. Protein samples were labeled with BODIPY FL-maleimide (dynamic range: > 4 orders of magnitude, detection limit: 5 f-mol) and resolved by two-dimensional gel electrophoresis (2D-GE). After normalizing the gel images, protein spots that exhibited differential abundance in any of the two groups were analyzed by mass spectrometry, and searched against UniProt human database for protein identification. We found 213 and 199 protein spots (fold change: |≥ 1.5|, p< 0.05) were differentially abundant in C/A and C/S individuals, respectively, with respect to N/H controls. Ingenuity Pathway Analysis (IPA) of PBMCs proteome dataset identified an increase in disorganization of cytoskeletal assembly and recruitment/activation and migration of immune cells in all chagasic subjects, though the invasion capacity of cells was decreased in C/S individuals. IPA predicted with high probability a decline in cell survival and free radical scavenging capacity in C/S (but not C/A) subjects. The MYC/SP1 transcription factors that regulate hypoxia and oxidative/inflammatory stress were predicted to be key targets in the context of control of Chagas disease severity. Further, MARS-modeling identified a panel of proteins that had >93% prediction success in classifying infected individuals with no disease and those with cardiac involvement and LV dysfunction. In conclusion, we have identified molecular pathways and a panel of proteins that could aid in detecting seropositive individuals at risk of developing cardiomyopathy.

Project description:BackgroundIn recent years advances have been made in the investigative methods of molecular background of canine heart disease. Studies have been conducted to identify specific genes which, when pathologically expressed, could lead to the dysfunction of the canine heart or are correlated with heart failure. For this purpose genome wide microarray experiments on tissues from failing hearts have been performed. In the presented study a whole genome microarray analysis was used for the first time to describe the transcription profile of peripheral blood nuclear cells in dogs with heart failure. Dogs with recognized heart disease were classified according the ISACHC (International Small Animal Cardiac Health Council) classification scheme as class 1 (asymptomatic)--13 dogs, class 2 (mild to moderate heart failure)--13 dogs and class 3 (severe heart failure)--12 dogs. The control group consisted of 14 healthy dogs. The clinical picture of the animals included: animal history, clinical examination, echocardiographic examination and where applicable electrocardiographic and radiographic examinations.ResultsIn the present study we identified four sets of differentially expressed genes, namely heart-failure-specific genes and ISACHC1-specific genes, ISACHC2-sepcific genes and ISACHC-3 specific genes. The most important set consisted of genes differentially expressed in all dogs with heart failure, despite the ISACHC stage. We identified 71 heart-failure-specific genes which were involved in two statistically significant receptor signalling pathways, namely angiotensinR -?>?CREB/ELK-SRF/TP53 signalling and ephrinR -?>?actin signalling. The number of ISACHC1-specific genes was 83; ISACHC2-specific genes--1247 and ISACHC3-specific--200.ConclusionsThe transcriptomic profile of peripheral blood nuclear cells in dogs with heart failure seems to reflect the presence of clinical signs of the disease in patients based on the observation that the largest number of differentially expressed genes was identified in ISACHC 2 group of patients. This group consists of dogs just starting to show clinical signs of heart failure. A set of genes was also found to have changed expression in all dogs with heart failure, despite the stage of the disease.

Dataset Information

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure.

Publications

S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure.

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