Effects of nitroglycerin or pentaerithrityl tetranitrate treatment on the gene expression in rat hearts: evidence for cardiotoxic and cardioprotective effects

2009 ◽  
Vol 38 (2) ◽  
pp. 176-185 ◽  
Author(s):  
Andrea Pautz ◽  
Peter Rauschkolb ◽  
Nadine Schmidt ◽  
Julia Art ◽  
Matthias Oelze ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Microarrays ◽  
Organic Nitrates ◽  
Genome Expression ◽  
Expression Of Genes ◽  
Rat Hearts ◽  
Enhanced Expression ◽  
Gene Transcripts ◽  
Cardioprotective Effects ◽  
Whole Genome Expression

Nitroglycerin (NTG) and pentaerithrityl tetranitrate (PETN) are organic nitrates used in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. Recent data show marked differences in the effects of NTG and PETN on the generation of reactive oxygen species. These differences are attributed to different effects of NTG and PETN on the expression of antioxidative proteins like the heme oxygenase-I. To analyze the expressional effects of NTG and PETN in a more comprehensive manner we performed whole genome expression profiling experiments using cardiac total RNA from NTG- or PETN-treated rats and DNA microarrays containing oligonucleotides representing 27,044 rat gene transcripts. The data obtained show that NTG and PETN together significantly modify the expression of >1,600 genes (NTG 532, PETN 1212). However, the expression of only a small group of these genes ( 68 ) was modified by both treatments, indicating marked differences in the expressional effects of NTG and PETN. NTG treatment resulted in the enhanced expression of genes that are believed to be markers for cardiotoxic processes. In addition, NTG treatment reduced the expression of genes described to code for cardioprotective proteins. In sharp contrast, PETN treatment enhanced the expression of cardioprotective genes and reduced the expression of genes believed to perform cardiotoxic effects. In conclusion, our data suggest that NTG treatment results in the induction of cardiotoxic gene expression networks leading to an activation of mechanisms that result in pathological changes in cardiomyocytes. In contrast, PETN treatment seems to activate gene expression networks that result in cardioprotective effects.

Anti-Diabetic Activity of a Mineraloid Isolate, in vitro and in Genetically Diabetic Mice

2011 ◽  
Vol 81 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Joel Deneau ◽  
Taufeeq Ahmed ◽  
Roger Blotsky ◽  
Krzysztof Bojanowski
Keyword(s):  
Dna Microarrays ◽  
Human Fibroblasts ◽  
Diabetic Animal ◽  
In Vitro Tests ◽  
Diabetic Mice ◽  
Fossil Material ◽  
Expression Of Genes ◽  
Enhanced Expression ◽  
Genetically Diabetic Mice

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.

scholarly journals Extracellular Phosphate Alters Cementoblast Gene Expression

2006 ◽  
Vol 85 (6) ◽  
pp. 505-509 ◽  
Author(s):  
R.B. Rutherford ◽  
B.L. Foster ◽  
T. Bammler ◽  
R.P. Beyer ◽  
S. Sato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Microarrays ◽  
Mouse Genome ◽  
Genetic Data ◽  
Phosphate Concentration ◽  
Transcription Factor Activity ◽  
Expression Of Genes ◽  
Time Period ◽  
Global Patterns ◽  
Genome Analyses

Genetic data from humans and mice reveal that the formation of cementum is sensitive to intra- and extracellular phosphate/pyrophosphate distribution. The intracellular molecular pathways whereby altered levels of extracellular phosphate concentration may affect cementum formation have not been elucidated. To initiate inquiry, we have studied the temporal effects of extracellular phosphate on global patterns of gene expression in a line of immortalized mouse cementoblasts. Total RNA from cultured cementoblasts treated with 5 mM inorganic phosphate over a designated time period, from 1–48 hrs, was analyzed for global patterns of gene expression by means of DNA microarrays representing the complete mouse genome. Analyses of significant hybridization signals indicated that 5 mM extracellular phosphate alters the expression of genes comprising several gene ontology (GO) groups, including transcription factor activity and Wnt signaling.

Whole genome expression as a quantitative trait

2009 ◽  
Vol 37 (6) ◽  
pp. 1276-1277 ◽  
Author(s):  
John Hardy ◽  
Danyah Trabzuni ◽  
Mina Ryten
Keyword(s):  
Gene Expression ◽  
Genetic Variability ◽  
Disease Risk ◽  
Neurological Diseases ◽  
Whole Genome ◽  
Genome Expression ◽  
Genome Analyses ◽  
Whole Genome Expression ◽  
Influence Gene Expression ◽  
Gene Expression Levels

Surprisingly, whole genome analyses of complex human neurological and psychiatric disorders have revealed that many genetic risk factors are likely to influence gene expression rather than alter protein sequences. Previous analyses of neurological diseases have shown that genetic variability in gene expression levels of deposited proteins influence disease risk. With this background, we have embarked on a comprehensive project to determine the effects of common genetic variability on whole genome gene expression.

Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays

2001 ◽  
Vol 5 (4) ◽  
pp. 161-170 ◽  
Author(s):  
DAVID GERHOLD ◽  
MEIQING LU ◽  
JIAN XU ◽  
CHRISTOPHER AUSTIN ◽  
C. THOMAS CASKEY ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Metabolism ◽  
Stress Responses ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Effects ◽  
Microarray Technology ◽  
Drug Candidates ◽  
Expression Of Genes

Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using microarray technology to minimize the long, expensive process of testing drug candidates for safety in animals. In an evaluation of hybridization specificity, microarray technology from Affymetrix distinguished genes up to a threshold of ∼90% DNA identity. Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be clearly distinguished by selecting a subset of oligonucleotides that hybridized selectively to CYP3A5. Further validation of the technology was performed by measuring gene expression profiles in livers of rats treated with vehicle, 3-methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by confirming data for six genes using quantitative RT-PCR. Responses of drug metabolism genes, including CYPs, epoxide hydrolases ( EHs), UDP-glucuronosyl transferases ( UGTs), glutathione sulfotransferases ( GSTs), sulfotransferases ( STs), drug transporter genes, and peroxisomal genes, to these well-studied compounds agreed well with, and extended, published observations. Additional gene regulatory responses were noted that characterize metabolic effects or stress responses to these compounds. Thus microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology.

scholarly journals Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis

2011 ◽  
Vol 43 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Kai Fang ◽  
Megan Bruce ◽  
Christopher B. Pattillo ◽  
Songlin Zhang ◽  
Randolph Stone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Profiling ◽  
Profile Analysis ◽  
Whole Genome ◽  
Qrt Pcr ◽  
Dss Colitis ◽  
Genome Expression ◽  
Expression Profile Analysis ◽  
Whole Genome Expression

Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r2 = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.

A modified pod specific promoter for high level heterologous expression of genes in legumes

2019 ◽  
Author(s):  
Aravind Kumar Konda ◽  
Pallavi Singh ◽  
Khela Ram Soren ◽  
Narendra Pratap Singh
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cis Acting ◽  
Inducible Promoters ◽  
Expression Of Genes ◽  
Enhanced Expression ◽  
High Level

Promoters are cis-acting regulatory elements that are usually present upstream to the coding sequences and determine the gene expression. Deployment of tissue specific and inducible promoters are constantly increasing for development of successful and stable multiple transgenic plants. To this end, as a strategy for enhanced expression of cis or transgenes, promoter engineering of the native msg promoter from soya bean has been carried out for executing pod specific expression of genes. Cis regulatory elements such as 5’UTR and poly (A) tract have been incorporated for imparting mRNA stability and translational enhancement to generate the modified 1.285 Kb pod specific promoter. Further to attain transcriptional enhancement the modified promoter has been cloned to generate Bi-directional Duplex Promoters (BDDP). The engineered msg promoter gene constructs can be deployed for high level tissue specific gene expression of cis/trans genes along with chosen terminator in chickpea. soybean and other legumes as well.

scholarly journals Sum1 and Ndt80 Proteins Compete for Binding to Middle Sporulation Element Sequences That Control Meiotic Gene Expression

2003 ◽  
Vol 23 (14) ◽  
pp. 4814-4825 ◽  
Author(s):  
Michael Pierce ◽  
Kirsten R. Benjamin ◽  
Sherwin P. Montano ◽  
Millie M. Georgiadis ◽  
Edward Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Dna Sequence ◽  
Whole Genome ◽  
Sequence Element ◽  
Genome Expression ◽  
Distinct Sequence ◽  
Whole Genome Expression ◽  
Sequence Requirements ◽  
Sporulation Genes

ABSTRACT A key transition in meiosis is the exit from prophase and entry into the nuclear divisions, which in the yeast Saccharomyces cerevisiae depends upon induction of the middle sporulation genes. Ndt80 is the primary transcriptional activator of the middle sporulation genes and binds to a DNA sequence element termed the middle sporulation element (MSE). Sum1 is a transcriptional repressor that binds to MSEs and represses middle sporulation genes during mitosis and early sporulation. We demonstrate that Sum1 and Ndt80 have overlapping yet distinct sequence requirements for binding to and acting at variant MSEs. Whole-genome expression analysis identified a subset of middle sporulation genes that was derepressed in a sum1 mutant. A comparison of the MSEs in the Sum1-repressible promoters and MSEs from other middle sporulation genes revealed that there are distinct classes of MSEs. We show that Sum1 and Ndt80 compete for binding to MSEs and that small changes in the sequence of an MSE can yield large differences in which protein is bound. Our results provide a mechanism for differentially regulating the expression of middle sporulation genes through the competition between the Sum1 repressor and the Ndt80 activator.

scholarly journals Regulation of Motility by the ExpR/Sin Quorum-Sensing System in Sinorhizobium meliloti

2007 ◽  
Vol 190 (3) ◽  
pp. 861-871 ◽  
Author(s):  
Hanh H. Hoang ◽  
Nataliya Gurich ◽  
Juan E. González
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Sinorhizobium Meliloti ◽  
Flagellar Apparatus ◽  
Sensing System ◽  
Physiological Processes ◽  
Genome Expression ◽  
Proposed Model ◽  
Quorum Sensing System ◽  
Whole Genome Expression

ABSTRACT A successful symbiotic relationship between Sinorhizobium meliloti and its host Medicago sativa (alfalfa) depends on several signaling mechanisms, such as the biosynthesis of exopolysaccharides (EPS) by S. meliloti. Previous work in our laboratory has shown that a quorum-sensing mechanism controls the production of the symbiotically active EPS II. Recent microarray analysis of the whole-genome expression profile of S. meliloti reveals that the ExpR/Sin quorum-sensing system regulates additional physiological processes that include low-molecular-weight succinoglycan production, nitrogen utilization, metal transport, motility, and chemotaxis. Nearly half of the flagellar genes and their dependence on quorum sensing are prominently displayed in our microarray analyses. We extend those observations in this work and confirm the findings by real-time PCR expression analysis of selected genes, including the flaF, flbT, flaC, cheY1, and flgB genes, involved in motility and chemotaxis. These genes code for regulators of flagellum synthesis, the chemotactic response, or parts of the flagellar apparatus. Gene expression analyses and visualization of flagella by electron microscopy performed at different points in the growth phase support our proposed model in which quorum sensing downregulates motility in S. meliloti. We demonstrate that the ExpR/Sin quorum-sensing system controls motility gene expression through the VisN/VisR/Rem relay. We also show that the ExoS-dependent two-component system suppresses motility gene expression through VisN and Rem in parallel to quorum sensing. This study contributes to our understanding of the mechanisms that govern motility in S. meliloti.

scholarly journals Regulation of Rugosity and Biofilm Formation in Vibrio cholerae: Comparison of VpsT and VpsR Regulons and Epistasis Analysis of vpsT, vpsR, and hapR

2007 ◽  
Vol 189 (2) ◽  
pp. 388-402 ◽  
Author(s):  
Sinem Beyhan ◽  
Kivanc Bilecen ◽  
Sofie R. Salama ◽  
Catharina Casper-Lindley ◽  
Fitnat H. Yildiz
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Epistasis Analysis ◽  
Genome Expression ◽  
Ggdef Domain ◽  
Whole Genome Expression ◽  
Virulence Factor Production

ABSTRACT Vibrio cholerae undergoes phenotypic variation that generates two morphologically different variants, termed smooth and rugose. The transcriptional profiles of the two variants differ greatly, and many of the differentially regulated genes are controlled by a complex regulatory circuitry that includes the transcriptional regulators VpsR, VpsT, and HapR. In this study, we identified the VpsT regulon and compared the VpsT and VpsR regulons to elucidate the contribution of each positive regulator to the rugose variant transcriptional profile and associated phenotypes. We have found that although the VpsT and VpsR regulons are very similar, the magnitude of the gene regulation accomplished by each regulator is different. We also determined that cdgA, which encodes a GGDEF domain protein, is partially responsible for the altered vps gene expression between the vpsT and vpsR mutants. Analysis of epistatic relationships among hapR, vpsT, and vpsR with respect to a whole-genome expression profile, colony morphology, and biofilm formation revealed that vpsR is epistatic to hapR and vpsT. Expression of virulence genes was increased in a vpsR hapR double mutant relative to a hapR mutant, suggesting that VpsR negatively regulates virulence gene expression in the hapR mutant. These results show that a complex regulatory interplay among VpsT, VpsR, HapR, and GGDEF/EAL family proteins controls transcription of the genes required for Vibrio polysaccharide and virulence factor production in V. cholerae.

scholarly journals Ultrasonic therapy modulates the expression of genes related to neovascularization and inflammation in fibroblasts

2021 ◽  
Vol 34 ◽  
Author(s):  
Priscila Daniele de Oliveira Perrucini ◽  
Rodrigo Franco de Oliveira ◽  
Flavia Beltrão Pires de Medeiros ◽  
Larissa Dragonetti Bertin ◽  
Deise Aparecida de Almeida Pires-Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Comparative Analysis ◽  
Cell Viability ◽  
Ultrasonic Therapy ◽  
Pulsed Ultrasound ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Mtt Method ◽  
Expression Of Genes ◽  
Gene Transcripts

Abstract Introduction: In the rehabilitation of musculoskeletal injuries, ultrasound is widely used in clinical practice. Objective: To evaluate the effects of pulsed ultrasonic therapy on the viability and modulation of genes involved in inflammation (IL-6) and neovascularization (VEGF) processes of L929 fibroblast cells. Methods: For irradiation with ultrasound the cells were subdivided into groups: G1 (without irradiation), G2 (0.3 W/cm2-20%) and G3 (0.6 W/cm2-20%), with periods of treatment at 24, 48 and 72 hours. The cell viability assay was analyzed by the MTT method and gene modulation was analyzed by RT-qPCR method. Results: After the comparative analysis between groups, only G2 and G3 (48-hour) presented statistically significant differences in relation to the control. In relation to the gene expression, the selection of the groups analyzed was delimited according to the comparative analysis of the values obtained by the MTT test. After the achievement of RT-qPCR, it could be observed that in G2 the amount of VEGF gene transcripts increased by 1.125-fold compared to endogenous controls, and increased 1.388-fold in G3. The IL-6 gene, on the other hand, had its transcripts reduced in both G2 (5.64x10-9) and G3 (1.91x10-6). Conclusion: Pulsed ultrasound in L929 fibroblasts showed a significant biostimulatory effect in the 48-hour period, with increased cell viability, and the same effect in the modulation of gene expression related the neovascularization and inflammation, mediating the acceleration of the tissue repair cascade.

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