scholarly journals Altered expression of genes for Kir ion channels in dilated cardiomyopathy

2013 ◽  
Vol 91 (8) ◽  
pp. 648-656 ◽  
Author(s):  
Viktoria Szuts ◽  
Dalma Ménesi ◽  
Zoltán Varga-Orvos ◽  
Ágnes Zvara ◽  
Nazanin Houshmand ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Expression Profiles ◽  
Systolic Dysfunction ◽  
Gene Expression Profiles ◽  
Left Ventricular ◽  
Altered Expression ◽  
Molecular Alterations ◽  
Expression Of Genes ◽  
Gene Coding ◽  
Left Ventricular Dilation

Dilated cardiomyopathy (DCM) is a multifactorial disease characterized by left ventricular dilation that is associated with systolic dysfunction and increased action potential duration. The Kir2.x K+ channels (encoded by KCNJ genes) regulate the inward rectifier current (IK1) contributing to the final repolarization in cardiac muscle. Here, we describe the transitions in the gene expression profiles of 4 KCNJ genes from healthy or dilated cardiomyopathic human hearts. In the healthy adult ventricles, KCNJ2, KCNJ12, and KCNJ4 (Kir2.1–2.3, respectively) genes were expressed at high levels, while expression of the KCNJ14 (Kir2.4) gene was low. In DCM ventricles, the levels of Kir2.1 and Kir2.3 were upregulated, but those of Kir2.2 channels were downregulated. Additionally, the expression of the DLG1 gene coding for the synapse-associated protein 97 (SAP97) anchoring molecule exhibited a 2-fold decline with increasing age in normal hearts, and it was robustly downregulated in young DCM patients. These adaptations could offer a new aspect for the explanation of the generally observed physiological and molecular alterations found in DCM.

The changes of gene expression profiles in hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts

2004 ◽  
Vol 14 (5) ◽  
pp. 984-997 ◽  
Author(s):  
J. Q. Cui ◽  
Y. F. Shi ◽  
H. J. Zhou ◽  
J. Q. Li
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cdna Microarray ◽  
Expression Profiles ◽  
Hydatidiform Mole ◽  
Gene Expression Profiles ◽  
Small Subunit ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Hydatidiform Moles

The purpose of this study is to investigate changes of gene expression profiles in hydatidiform moles (HM) and choriocarcinoma and to explore causes of trophoblastic hyperplasia. Using cDNA microarray, 4096 genes were analyzed in two pairs of the tissues of HM versus normal villi and in two pairs of normal primary culture trophoblasts versus JAR cell line of choriocarcinoma. The expressions of two genes in normal villi and HM, as well as in JAR and JEG-3, were examined with the help of immunohistochemistry, immunoblot, and reverse transcriptase-polymerase chain reaction in order to confirm the findings of cDNA microarray. Twenty-four genes were upregulated and 65 genes were downregulated in all HM. Four hundred thirty-three genes were upregulated and 380 genes were downregulated in JAR. Forty-six genes were upregulated in both HM and choriocarcinoma, whereas 13 genes were downregulated. Genes associated with the inhibition of cell proliferation were significantly downregulated, whereas genes associated with cell proliferation, malignant transformation, metastasis, and drug resistance were upregulated. Thymidine kinase-1 (TK-1) and small subunit ribonucleotide reductase (RRM-2) were overexpressed in HM, JAR, and JEG-3. The expressions of TK-1 and RRM-2 in moles were positively correlated with proliferative index of trophoblasts. Our results suggest that altered expression of genes exist in HM and choriocarcinoma. Trophoblastic hyperplasia may be involved in the overexpression of DNA synthetic enzymes.

scholarly journals Modifications of Titin Contribute to the Progression of Cardiomyopathy and Represent a Therapeutic Target for Treatment of Heart Failure

2020 ◽  
Vol 9 (9) ◽  
pp. 2770 ◽  
Author(s):  
Charles Tharp ◽  
Luisa Mestroni ◽  
Matthew Taylor
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Diastolic Dysfunction ◽  
Therapeutic Target ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Post Translational Modifications ◽  
Left Ventricular Dilation ◽  
Molecular Springs

Titin is the largest human protein and an essential component of the cardiac sarcomere. With multiple immunoglobulin(Ig)-like domains that serve as molecular springs, titin contributes significantly to the passive tension, systolic function, and diastolic function of the heart. Mutations leading to early termination of titin are the most common genetic cause of dilated cardiomyopathy. Modifications of titin, which change protein length, and relative stiffness affect resting tension of the ventricle and are associated with acquired forms of heart failure. Transcriptional and post-translational changes that increase titin’s length and extensibility, making the sarcomere longer and softer, are associated with systolic dysfunction and left ventricular dilation. Modifications of titin that decrease its length and extensibility, making the sarcomere shorter and stiffer, are associated with diastolic dysfunction in animal models. There has been significant progress in understanding the mechanisms by which titin is modified. As molecular pathways that modify titin’s mechanical properties are elucidated, they represent therapeutic targets for treatment of both systolic and diastolic dysfunction. In this article, we review titin’s contribution to normal cardiac physiology, the pathophysiology of titin truncation variations leading to dilated cardiomyopathy, and transcriptional and post-translational modifications of titin. Emphasis is on how modification of titin can be utilized as a therapeutic target for treatment of heart failure.

scholarly journals Genetic Determinant of Familial Dilated Cardiomyopathy and Genotype-Targeted Therapeutic Strategy

2020 ◽  
Author(s):  
Jing Zhong ◽  
Li-Ping Li ◽  
Jian-Feng Zhou ◽  
Yong-He Ding
Keyword(s):  
Dilated Cardiomyopathy ◽  
Therapeutic Strategy ◽  
Individualized Medicine ◽  
Systolic Dysfunction ◽  
Disease Diagnosis ◽  
Left Ventricular ◽  
Familial Dilated Cardiomyopathy ◽  
Left Ventricular Dilation ◽  
Improve Patient ◽  
Targeted Therapeutic

Dilated cardiomyopathy (DCM) is a myocardium disease characterized by left ventricular dilation and systolic dysfunction. Genetic susceptibility contributes significantly to the disease progression in familial DCM. Mutations in more than fifty different genes have been identified to cause DCM, accounting for up to 50% of familial DCM cases. Elucidation of genetic basis for the remaining familial DCM probands promises to substantially increase the efficiency of genetic testing for early disease diagnosis and intervention. Dissecting genetic pathways linked to DCM and related pathogenic mechanisms can provide valuable insights into the understanding of disease pathophysiology that can be leveraged for development of genotype-targeted therapeutic strategy. Here, we review genetic variants, with a focus on affected genes most commonly implicated in DCM, and highlight their underlying pathophysiological mechanisms of action. We discuss recent progress on gene-based therapeutic strategy which holds the opportunities to implement individualized medicine and ultimately to improve patient outcome in the future.

scholarly journals The transcriptome profile of human trisomy 21 blood cells

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Francesca Antonaros ◽  
Rossella Zenatelli ◽  
Giulia Guerri ◽  
Matteo Bertelli ◽  
Chiara Locatelli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Normal Control ◽  
Blood Cells ◽  
Trisomy 21 ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Published Data ◽  
Mitochondrial Translation ◽  
Altered Expression ◽  
Expression Of Genes

Abstract Background Trisomy 21 (T21) is a genetic alteration characterised by the presence of an extra full or partial human chromosome 21 (Hsa21) leading to Down syndrome (DS), the most common form of intellectual disability (ID). It is broadly agreed that the presence of extra genetic material in T21 gives origin to an altered expression of genes located on Hsa21 leading to DS phenotype. The aim of this study was to analyse T21 and normal control blood cell gene expression profiles obtained by total RNA sequencing (RNA-Seq). Results The results were elaborated by the TRAM (Transcriptome Mapper) software which generated a differential transcriptome map between human T21 and normal control blood cells providing the gene expression ratios for 17,867 loci. The obtained gene expression profiles were validated through real-time reverse transcription polymerase chain reaction (RT-PCR) assay and compared with previously published data. A post-analysis through transcriptome mapping allowed the identification of the segmental (regional) variation of the expression level across the whole genome (segment-based analysis of expression). Interestingly, the most over-expressed genes encode for interferon-induced proteins, two of them (MX1 and MX2 genes) mapping on Hsa21 (21q22.3). The altered expression of genes involved in mitochondrial translation and energy production also emerged, followed by the altered expression of genes encoding for the folate cycle enzyme, GART, and the folate transporter, SLC19A1. Conclusions The alteration of these pathways might be linked and involved in the manifestation of ID in DS.

scholarly journals Dose-response relationships in gene expression profiles in a harbor seal B lymphoma cell line exposed to 17α-ethinyl estradiol

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Christine Kleinert ◽  
Matthieu Blanchet ◽  
François Gagné ◽  
Michel Fournier
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Ethinyl Estradiol ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Harbor Seal ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Altered Expression ◽  
B Lymphoma

The determination of changes in gene expression profiles with xenobiotic dose will allow identifying biomarkers and modes of toxicant action. The harbor seal (Phoca vitulina) 11B7501 B lymphoma cell line was exposed to 1, 10, 100, 1000, 10,000, or 25,000 μg/L 17α-ethinyl estradiol (EE2, the active compound of the contraceptive pill) for 24 h. Following exposure, RNA was extracted and transformed into cDNA. Transcript expression in exposed vs. control lymphocytes was analyzed via RT-qPCR to identify genes with altered expression. Our analysis indicates that gene expression for all but the reference gene varied with dose, suggesting that different doses induce distinct physiological responses. These findings demonstrate that RT-qPCR could be used to identify immunotoxicity and relative dose in harbor seal leukocytes.

scholarly journals Fusarium verticillioides FvPex8 is a key component of peroxisomal docking/translocation module that serves important roles in fumonisin biosynthesis but not in virulence

2020 ◽  
Author(s):  
Wenying Yu ◽  
Mei Lin ◽  
Minghui Peng ◽  
Huijuan Yan ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Fusarium Verticillioides ◽  
Fumonisin B1 ◽  
Gene Expression Profiles ◽  
Deletion Mutants ◽  
Altered Expression ◽  
The Core ◽  
Metabolic Functions ◽  
Peroxisome Membrane

AbstractPeroxisomes are ubiquitous organelles in eukaryotic cells that fulfill various important metabolic functions. In this study, we investigated the role of Docking/Translocation Module (DTM) peroxins, mainly FvPex8, FvPex13, FvPex14, and FvPex33, in Fusarium verticillioides virulence and fumonisin B1 (FB1) biosynthesis. Protein interaction experiments suggested that FvPex13 serves as the core subunit of F. verticillioides DTM. When we generated gene deletion mutants (ΔFvpex8, ΔFvpex13, ΔFvpex14, ΔFvpex33, ΔFvpex33/14) and examined whether the expression of other peroxin genes were affected in the DTM mutants, ΔFvpex8 strain showed most drastic changes to PEX gene expression profiles. Deletion mutants exhibited disparity in carbon source utilization and defect in cell wall integrity when stress agents were applied. Under nutrient starvation, mutants also showed higher levels of lipid droplet accumulation. Notably, ΔFvpex8 mutant showed significant FB1 reduction and altered expression of FUM1 and FUM19 genes. However, FvPex13 was primarily responsible for virulence, while ΔFvpex33/14 double mutant also showed virulence defect. In summary, our study suggests that FvPex13 is the core component of DTM, regulating peroxisome membrane biogenesis as well as PTS1- and PTS2-mediated transmembrane cargo transportation. Importantly, we predict FvPex8 as a key component in DTM that affects peroxisome function in FB1 biosynthesis in F. verticillioides.

scholarly journals Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis

2020 ◽  
Author(s):  
Benedicto Crespo-Facorro ◽  
Miguel Ruiz-Veguilla ◽  
Javier Vazquez-Bourgon ◽  
Ana C. Sanchez-Hidalgo ◽  
Nathalia Garrido-Torres ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Phase 1 ◽  
Gene Expression Profiles ◽  
Genomic Analysis ◽  
Cell Receptor ◽  
Therapeutic Drug ◽  
P Value ◽  
Immunological Parameters ◽  
Altered Expression ◽  
Exact Test

Background: Antipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naive patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher's Exact Test, two tail; P value=3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the inflammatory bowel disease (IBD) (the most significant pathway with a P adj of 0.00021), Th1 and Th2 cell differentiation and B cell receptor signaling pathway, all three related to the defense against infections. Interpretation: This exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.

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