scholarly journals Costameric Integrin and Sarcoglycan protein levels are altered in a Drosophila model for Limb Girdle Muscular Dystrophy type 2H

2020 ◽  
pp. mbc.E20-07-0453
Author(s):  
Simranjot Bawa ◽  
Samantha Gameros ◽  
Kenny Baumann ◽  
David S. Brooks ◽  
Joseph A. Kollhoff ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Limb Girdle Muscular Dystrophy ◽  
Nuclear Morphology ◽  
Muscle Degeneration ◽  
Transgenic Expression ◽  
Protein Levels ◽  
Drosophila Model ◽  
Core Components ◽  
First Time

Mutations in two different domains of the ubiquitously expressed TRIM32 protein give rise to two clinically separate diseases, one of which is Limb-girdle muscular dystrophy type 2H (LGMD2H). Uncovering the muscle-specific role of TRIM32 in LGMD2H pathogenesis has proven difficult as neurogenic phenotypes, independent of LGMD2H pathology, are present in TRIM32 KO mice. We previously established a platform to study LGMD2H pathogenesis using Drosophila melanogaster as a model. Here we show that LGMD2H disease-causing mutations in the NHL domain are molecularly and structurally conserved between fly and human TRIM32. Furthermore, transgenic expression of a subset of myopathic alleles (R394H, D487N and 520fs) induce myofibril abnormalities, altered nuclear morphology and reduced TRIM32 protein levels, mimicking phenotypes in patients afflicted with LGMD2H. Intriguingly, we also report for the first time that the protein levels of βPS integrin and Sarcoglycan δ, both core components of costameres, are elevated in TRIM32 disease-causing alleles. Similarly, murine myoblasts overexpressing a catalytically inactive TRIM32 mutant, aberrantly accumulate α- and β-Dystroglycan and α-Sarcoglycan. We speculate that the stoichiometric loss of costamere components disrupts costamere complexes to promote muscle degeneration.

Codon usage and protein sequence pattern dependency in different organisms: A Bioinformatics approach

2015 ◽  
Vol 13 (02) ◽  
pp. 1550002
Author(s):  
Mohammad-Hadi Foroughmand-Araabi ◽  
Bahram Goliaei ◽  
Kasra Alishahi ◽  
Mehdi Sadeghi ◽  
Sama Goliaei
Keyword(s):  
Gene Regulation ◽  
Codon Usage ◽  
Protein Sequence ◽  
Multinomial Logistic Regression ◽  
Translation Efficiency ◽  
Translation Rate ◽  
Protein Levels ◽  
Synonymous Codons ◽  
First Time

Although it is known that synonymous codons are not chosen randomly, the role of the codon usage in gene regulation is not clearly understood, yet. Researchers have investigated the relation between the codon usage and various properties, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Recently, a universal codon usage based mechanism for gene regulation is proposed. We studied the role of protein sequence patterns on the codons usage by related genes. Considering a subsequence of a protein that matches to a pattern or motif, we showed that, parts of the genes, which are translated to this subsequence, use specific ratios of synonymous codons. Also, we built a multinomial logistic regression statistical model for codon usage, which considers the effect of patterns on codon usage. This model justifies the observed codon usage preference better than the classic organism dependent codon usage. Our results showed that the codon usage plays a role in controlling protein levels, for genes that participate in a specific biological function. This is the first time that this phenomenon is reported.

Abstract 285: Osteopontin Deficiency Ameliorates Heart Failure with Preserved Ejection Fraction Pathology by Upregulating Mitochondrial 2-Oxoglutarate Dehydrogenase Like Enzyme

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Keyvan Yousefi ◽  
Wen Ding ◽  
Lina A Shehadeh
Keyword(s):  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Interstitial Fibrosis ◽  
Matricellular Protein ◽  
Double Knockout ◽  
Protein Levels ◽  
Lower Protein ◽  
Myocardial Energetics ◽  
First Time

HFpEF is an increasingly prevalent syndrome associated with impaired myocardial energetics, for which no etiologic therapy is available. Osteopontin (OPN) is a matricellular protein that is upregulated in the circulation of HFpEF patients, and reported to induce mitochondrial stress in rodent cardiomyocytes. Here we evaluate the role of circulating OPN in regulating myocardial function in the nephrotic Col4a3 -/- mouse model of HFpEF. We performed extensive cardiac, biochemical and mitochondrial analyses of the Col4a3 -/- mouse and found a striking HFpEF phenotype. We showed OPN levels were elevated in Col4a3 -/- mice (FC=2.1, n=6; p<.01). Col4a3 -/- mice were hypertensive, had diastolic dysfunction, myocyte hypertrophy and interstitial fibrosis - all of which were ameliorated in Col4a3 -/- OPN -/- mice (n=5-20; p<.05). Col4a3 -/- hearts had dysmorphic mitochondria (EM), lowered antioxidant capacity as a 50% reduction in GSH/GSSG ratio (n=6; p<.05) and lower protein levels of mitochondrial respiratory complexes I, II and IV (p<.05). Flux assay in adult cardiomyocytes showed that maximal respiration was reduced in Col4a3 -/- hearts (575.84±37.6 vs 322.34±25.48 pmol/min in WT, n=9; p<.0001). Microarray data (validated by mitochondrial blot) implicated OGDHL as decreased in Col4a3 -/- hearts but increased in double knockout Col4a3 -/- OPN -/- hearts compared to WT (n=3; p<.05). OGDH activity was also lower in Col4a3 -/- hearts (17.1±7.3 vs 2.5±1.1 mU/mg in WT; n=6; p<.05). In Col4a3 -/- mice, heart-specific AAV9-mediated overexpression of OGDHL, similar to global OPN KO, improved survival by ~50-100% (p<.0001). Isovolumetric relaxation time, a marker of diastolic dysfunction, which is prolonged in Col4a3 -/- mice (26.17 vs 15.30±1 ms, n=26; p<.001) was decreased in Col4a3 -/- OPN -/- mice (18.1±1 ms, n=37; p<.01) as well as in AAV9-cTnT-OGDHL-treated Col4a3 -/- mice (16.7±2.5 ms, n=8; p<.05). In conclusion, we present a new mouse model for HFpEF in which diastolic function and lifespan can be improved by genetic deletion of OPN or cardiac OGDHL gene therapy. Our results elucidate for the first time the pivotal roles of circulating OPN and cardiac OGDHL in HFpEF pathophysiology and present two related potential therapeutic targets for HFpEF.

scholarly journals The Role of OXT, OXTR, AVP, and AVPR1a Gene Expression in the Course of Schizophrenia

2022 ◽  
Vol 44 (1) ◽  
pp. 336-349
Author(s):  
Marta Broniarczyk-Czarniak ◽  
Janusz Szemraj ◽  
Janusz Śmigielski ◽  
Piotr Gałecki
Keyword(s):  
Gene Expression ◽  
Early Adulthood ◽  
Depression Scale ◽  
Emotional Behavior ◽  
Social And Emotional ◽  
Protein Levels ◽  
Syndrome Scale ◽  
Negative Syndrome ◽  
First Time

Schizophrenia is a serious and chronic mental illness, the symptoms of which usually appear for the first time in late adolescence or early adulthood. To date, much research has been conducted on the etiology of schizophrenia; however, it is still not fully understood. Oxytocin and vasopressin as neuromodulators that regulate social and emotional behavior are promising candidates for determining the vulnerability to schizophrenia. The aim of this study was to evaluate the expression of OXT, OXTR, AVP, and AVPR1a genes at the mRNA and protein levels in patients with schizophrenia. Due to the neurodegenerative nature of schizophrenia, the study group was divided into two subgroups, namely, G1 with a diagnosis that was made between 10 and 15 years after the onset of the illness, and G2 with a diagnosis made up to two years after the onset of the illness. Moreover, the relationship between the examined genes and the severity of schizophrenia symptoms, assessed using PANSS (Positive and Negative Syndrome Scale) and CDSS scales (Clinical Depression Scale for Schizophrenia) was evaluated. The analysis of the expression of the studied genes at the mRNA and protein levels showed statistically significant differences in the expression of all the investigated genes. OXT and AVPR1a gene expression at both the mRNA and protein levels were significantly lower in the schizophrenia group, and OXTR and AVP gene expression at both the mRNA and protein levels was higher in the schizophrenia subjects than in the controls. Furthermore, a significant correlation of OXT gene expression at the mRNA and protein levels with the severity of depressive symptoms in schizophrenia as assessed by CDSS was found.

scholarly journals RNAs 1 and 2 of Alfalfa mosaic virus, expressed in transgenic plants, start to replicate only after infection of the plants with RNA 3

2001 ◽  
Vol 82 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Vera Thole ◽  
Maria-Laura Garcia ◽  
Clemens M. A. van Rossum ◽  
Lyda Neeleman ◽  
Frans T. Brederode ◽  
...  
Keyword(s):  
Mosaic Virus ◽  
Rna Synthesis ◽  
Alfalfa Mosaic Virus ◽  
Transgenic Expression ◽  
Whole Plant ◽  
Transgenic Lines ◽  
Viral Replicase ◽  
Plant Level ◽  
First Time

RNAs 1 and 2 of the tripartite genome of Alfalfa mosaic virus (AMV) encode the two viral replicase subunits. Full-length DNA copies of RNAs 1 and 2 were used to transform tobacco plants (R12 lines). None of the transgenic lines showed resistance to AMV infection. In healthy R12 plants, the transcripts of the viral cDNAs were copied by the transgenic viral replicase into minus-strand RNAs but subsequent steps in replication were blocked. When the R12 plants were inoculated with AMV RNA 3, this block was lifted and the transgenic RNAs 1 and 2 were amplified by the transgenic replicase together with RNA 3. The transgenic expression of RNAs 1 and 2 largely circumvented the role of coat protein (CP) in the inoculum that is required for infection of nontransgenic plants. The results for the first time demonstrate the role of CP in AMV plus-strand RNA synthesis at the whole plant level.

scholarly journals The role of magnetic resonance imaging of muscles in the differential diagnosis of certain forms and subtypes of limb-girdle muscular dystrophy: case analysis

2021 ◽  
Vol 16 (8) ◽  
pp. 43-47
Author(s):  
H.V. Palahuta ◽  
O.Ye. Fartushna
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Muscular Dystrophy ◽  
Correct Diagnosis ◽  
Integrated Approach ◽  
Limb Girdle Muscular Dystrophy ◽  
Resonance Imaging ◽  
Laboratory Methods ◽  
Progressive Muscular Dystrophy

Limb-girdle muscular dystrophy is a genetically heterogeneous group of disorders that are characterized by slowly progressing muscle weakness and presents a diagnostic problem in the neurological practice. The combination of clinical, radiological, and laboratory methods of examination plays an important role in referring the patient to genetic counseling and making the correct diagnosis. Magnetic resonance imaging of muscles is increasingly used to give clues in the primary muscle damage diagnosis, based on specific patterns of muscle lesion. The article provides two clinical cases as an example of an integrated approach to the diagnosis of progressive muscular dystrophy using genetic analysis and magnetic resonance imaging of muscles

scholarly journals D-Aspartate Upregulates DAAM1 Protein Levels in the Rat Testis and Induces Its Localization in Spermatogonia Nucleus

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 677 ◽  
Author(s):  
Massimo Venditti ◽  
Alessandra Santillo ◽  
Sara Falvo ◽  
Maria Maddalena Di Fiore ◽  
Gabriella Chieffi Baccari ◽  
...  
Keyword(s):  
Germ Cells ◽  
Actin Polymerization ◽  
Excitatory Amino Acid ◽  
Chromatin Condensation ◽  
Actin Dynamics ◽  
Rat Testis ◽  
Protein Levels ◽  
First Time ◽  
Mitosis And Meiosis

Cell differentiation during spermatogenesis requires a proper actin dynamic, regulated by several proteins, including formins. Disheveled-Associated-Activator of Morphogenesis1 (DAAM1) belongs to the formins and promotes actin polymerization. Our results showed that oral D-Aspartate (D-Asp) administration, an excitatory amino acid, increased DAAM1 protein levels in germ cells cytoplasm of rat testis. Interestingly, after the treatment, DAAM1 also localized in rat spermatogonia (SPG) and mouse GC-1 cells nuclei. We provided bioinformatic evidence that DAAM1 sequence has two predicted NLS, supporting its nuclear localization. The data also suggested a role of D-Asp in promoting DAAM1 shuttling to the nuclear compartment of those proliferative cells. In addition, the proliferative action induced by D-Asp is confirmed by the increased levels of PCNA, a protein expressed in the nucleus of cells in the S phase and p-H3, a histone crucial for chromatin condensation during mitosis and meiosis. In conclusion, we demonstrated, for the first time, an increased DAAM1 protein levels following D-Asp treatment in rat testis and also its localization in the nucleus of rat SPG and in mouse GC-1 cells. Our results suggest an assumed role for this formin as a regulator of actin dynamics in both cytoplasm and nuclei of the germ cells.

Muscular dystrophy: Possible role of mitochondrial deficiency in muscle degeneration processes

1990 ◽  
Vol 95 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Brigitte Lucas-Heron ◽  
Nelly Schmitt ◽  
Béatrice Ollivier
Keyword(s):  
Muscular Dystrophy ◽  
Muscle Degeneration

scholarly journals The role of cell transplantation in modifying the course of limb girdle muscular dystrophy: a longitudinal 5-year study

2015 ◽  
pp. 93 ◽  
Author(s):  
Amruta Paranjape ◽  
Alok Sharma ◽  
Hemangi Sane ◽  
Nandini Gokulchandran ◽  
Sushant Gandhi ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Cell Transplantation ◽  
Limb Girdle Muscular Dystrophy

scholarly journals Estradiol differentially regulates DUX4, β-catenin and PAX3/PAX7 in primary myoblasts of facioscapulohumeral muscular dystrophy patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ceren Hangul ◽  
Esin Guvenir Celik ◽  
Hacer Kaya ◽  
Onur Eroglu ◽  
Hilmi Uysal ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Palliative Treatment ◽  
Protective Factor ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Protective Role ◽  
Estradiol Treatment ◽  
Protein Levels ◽  
Primary Myoblasts

AbstractObjectivesThere is a clinical variability and heterogeneity among Facioscapulohumeral Muscular Dystrophy (FSHD) patients. Escalation after menopause in women, early onset in men suggests that estrogen might be a protective factor on the course of FSHD. In spite of few molecular studies supporting the protective role of estrogen in FSHD in vitro, there is no study revealing the effect of estradiol on the protein levels of DUX4, β-catenin and PAX3/PAX7. In present study, we investigated the effect of estradiol treatment on the expressions of DUX4, β-catenin and PAX3/PAX7 protein levels.Materials and MethodsPrimary myoblasts of 63 and 71 years old (63yM/71yM) males; 47 years old (47yF) female FSHD patients were used. Cells were processed under these conditions; (i) untreated, (ii) 10 nM-30 min estradiol and (iii) 10 nM-4 h estradiol treated. The expression of DUX4, PAX3/PAX7 and β-catenin were examined by western-blotting.ResultsExpression of DUX4 significantly downregulated after 4 h treatment of estradiol while PAX3/PAX7 56 kDa variant expression upregulated in 71yM cells. β-catenin and PAX3 expression was variable among the samples.ConclusionOur results suggest that estrogen might be a palliative treatment option via downregulation of DUX4 protein in DUX4 expressing FSHD patients.

Sign in / Sign up

Export Citation Format

Share Document