Comparative hepatic gene expression profiling of rats treated with 1H,1H,2H,2H-heptadecafluorodecan-1-ol or with pentadecafluorooctanoic acid

2008 ◽  
Vol 34 (3) ◽  
pp. 285-303 ◽  
Author(s):  
Anja Julie Nilsen ◽  
Maria A. Landin ◽  
Kristin H. Haug ◽  
Frode Fonnum ◽  
Urs Berger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Radical Scavenging ◽  
Bioinformatic Analysis ◽  
Progressive Increase ◽  
Peroxisome Proliferator ◽  
Hepatic Gene Expression ◽  
Expression Data ◽  
Rt Pcr ◽  
Pathways Analysis ◽  
Regulatory Functions

Pentadecafluorooctanoic acid is an established peroxisome proliferator. Little is known about effects of treatment with 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol, which is metabolized to pentadecafluorooctanoic acid. We compared effects of various dosages (3, 10, or 25 mg/kg body wt) of each of these compounds on hepatic gene expression in rats with microarrays. Microarray data were validated by real-time RT-PCR. Expression data were also correlated with hepatic activities of selected enzymes and with hepatic levels of pentadecafluorooctanoic acid and 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol. Pentadecafluorooctanoic acid caused the more powerful change in gene expression, in terms of both number of genes affected and extent of change in expression. Across the dosages used pentadecafluorooctanoic acid and 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol caused significant ( P ≤ 0.05) changes in expression for 441 and 105 genes, respectively. With 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol ∼38% of the 105 genes exhibited decreased expression with a dose of 25 mg/kg body wt, these genes also appearing less responsive to treatment at the lower dosages. Bioinformatic analysis suggested that these genes are associated with regulatory functions. With pentadecafluorooctanoic acid, increasing dosage up to 10 mg/kg body wt brought about progressive increase in expression of affected genes. Pathways analysis suggested similar effects of the two compounds on lipid and amino acid metabolism. Marked differences were also found, particularly with respect to effects on genes related to oxidative phosphorylation, oxidative metabolism, free radical scavenging, xenobiotic metabolism, and complement and coagulation cascades.

Three-color cDNA microarrays with prehybridization quality control yield gene expression data comparable to that of commercial platforms

2006 ◽  
Vol 25 (1) ◽  
pp. 166-178 ◽  
Author(s):  
Martin J. Hessner ◽  
Bixia Xiang ◽  
Shuang Jia ◽  
Rhonda Geoffrey ◽  
Shannon Holmes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quality Control ◽  
Gene Expression Data ◽  
Lower Cost ◽  
Cdna Array ◽  
Correlation Coefficients ◽  
Expression Data ◽  
Data Filtering ◽  
Rt Pcr ◽  
Cdna Arrays

Despite their lower cost and high content flexibility, a limitation of in-house-prepared arrays has been their susceptibility to quality control (QC) issues and lack of QC standards across laboratories. Therefore, we developed a novel three-color array system that allows prehybridization QC as well as the Matarray software to facilitate acquisition of accurate gene expression data. In this study, we compared performance of our rat cDNA array to the Affymetrix RG-U34A and Agilent G4130A arrays using 2,824 UniGenes represented on all three arrays. Before data filtering, poor interplatform agreement was observed; however, after data filtering, differentially expressed UniGenes exhibited correlation coefficients of 0.91, 0.88, and 0.92 between the Affymetrix vs. Agilent, Affymetrix vs. cDNA, and Agilent vs. cDNA arrays, respectively. The Affymetrix, Agilent, and cDNA arrays agreed well with quantitative RT-PCR conducted on 42 UniGenes, yielding correlation coefficients of 0.90, 0.90, and 0.96, respectively. Each platform underestimated ratios relative to quantitative RT-PCR, possessing respective slopes of 0.86 ( R2 = 0.81), 0.65 ( R2 = 0.81), and 0.70 ( R2 = 0.92). Overall, these data show that the combination of our novel technical and analytic approaches yield an accurate platform for functional genomics that is concordant with commercial discovery arrays in terms of identifying regulated genes and pathways.

Insights into Responses to Extreme Environmental Conditions in Humans from Studies on Saccharomyces cerevisiae

2015 ◽  
Vol 65 (6) ◽  
pp. 444
Author(s):  
Ramesh C. Meena ◽  
Amitabha Chakrabarti
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Stress Response ◽  
Gene Expression Data ◽  
Molecular Mechanisms ◽  
Multiple Stressors ◽  
Expression Data ◽  
Environmental Stress Response ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pathways Analysis

<p>The versatility of the yeast experimental model has aided in innumerable ways in the understanding of fundamental cellular functions and has also contributed towards the elucidation of molecular mechanisms underlying several pathological conditions in humans. Genome-wide expression, functional, localization and interaction studies on the yeast Saccharomyces cerevisiae exposed to various stressors have made profound contributions towards the understanding of stress response pathways. Analysis of gene expression data from S. cerevisiae cells indicate that the expression of a common set of genes is altered upon exposure to all the stress conditions examined. This common response to multiple stressors is known as the Environmental stress response. Knowledge gained from studies on the yeast model has now become helpful in understanding stress response pathways and associated disease conditions in humans. Cross-species microarray experiments and analysis of data with ever improving computational methods has led to a better comparison of gene expression data between diverse organisms that include yeast and humans.</p>

scholarly journals Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Bioinformatic Analysis ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Anthracycline Cardiotoxicity ◽  
Breast Cancer Chemotherapy

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.

scholarly journals Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile inWfs1Knockout Mouse

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Marite Punapart ◽  
Mall Eltermaa ◽  
Julia Oflijan ◽  
Silva Sütt ◽  
Anne Must ◽  
...  
Keyword(s):  
Gene Expression ◽  
Valproic Acid ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Expression Profiles ◽  
Peroxisome Proliferator ◽  
Hepatic Gene Expression ◽  
Wild Type ◽  
Drug Induced

Valproic acid (VPA) is a widely used anticonvulsant and mood-stabilizing drug whose use is often associated with drug-induced weight gain. Treatment with VPA has been shown to upregulateWfs1expressionin vitro. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) andWfs1knockout (KO) mice on hepatic gene expression profile. Wild type,Wfs1heterozygous, and homozygous mice were treated with VPA for three months (300 mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0 ST array. We identified 42 genes affected byWfs1genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (Ppard), whose expression was upregulated in response to VPA treatment in WT, but not inWfs1KO mice. Thus, regulation ofPpardby VPA is dependent onWfs1genotype.

scholarly journals Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Bioinformatic Analysis ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Anthracycline Cardiotoxicity ◽  
Breast Cancer Chemotherapy

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.

scholarly journals PAX8 and peroxisome proliferator-activated receptor gamma 1 gene expression status in benign and malignant thyroid tissues

2004 ◽  
pp. 367-374 ◽  
Author(s):  
L Lacroix ◽  
C Mian ◽  
T Barrier ◽  
M Talbot ◽  
B Caillou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Neoplasms ◽  
Genetic Alterations ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Peroxisome Proliferator Activated Receptor ◽  
Normal Tissues ◽  
Pax8 Gene ◽  
Follicular Tumors

OBJECTIVE: Genetic alterations involving the thyroid transcription factor PAX8 and the peroxisome proliferator-activated receptor gamma 1 (PPARgamma1) genes have been described in thyroid neoplasms. We investigated in a series of thyroid samples, including 14 normal, 13 hyperfunctioning tissues, 26 follicular adenomas, 21 follicular and 41 papillary carcinomas, both the frequency of the PAX8-PPARgamma1 rearrangement and the expression of the PAX8 and PPARgamma transcripts. METHODS: Using RT-PCR followed by sequencing PCR products, PAX8-PPARgamma1 translocation was not detected in benign tissues nor in papillary carcinomas and was detected in 4 (19%) of 21 follicular carcinomas and in one (4%) of 26 follicular adenomas. RESULTS: Specific real-time quantitative RT-PCR (Q RT-PCR) methods detected high levels of PPARgamma transcripts in follicular carcinomas presenting the rearrangement. Interestingly, the level of PPARgamma transcripts was significantly decreased in papillary carcinomas in comparison with those found in benign adenomas and follicular carcinomas. Finally, PAX8 gene expression was decreased in both papillary and follicular thyroid carcinomas, and in these tumors to the same extent in the presence or absence of the rearrangement. These alterations in both PPARgamma and PAX8 gene expression may explain the poorly differentiated histotype of follicular carcinomas harboring the translocation.Immunohistochemistry showed that nuclear PPARgamma staining was weak in normal tissues, adenomas, papillary carcinomas and in some follicular carcinomas, and strong in the follicular carcinomas positive for the PAX8-PPARgamma1 translocation, but also in some follicular tumors in which no translocation could be evidenced. CONCLUSION: These observations confirm that the PAX8-PPARgamma1 translocation characterizes a subset of thyroid follicular carcinomas but is not a specific marker of carcinoma and that its frequency is lower than that initially reported. Finally, immunohistochemistry is not a reliable method for the specific detection of the translocation, that can be specifically evidenced by Q RT-PCR.

scholarly journals Indication of Premelanosome Protein (PMEL) Expression Outside of Pigmented Bovine Skin Suggests Functions Beyond Eumelanogenesis

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 788
Author(s):  
Jacqueline Knaust ◽  
Rosemarie Weikard ◽  
Elke Albrecht ◽  
Ronald M. Brunner ◽  
Juliane Günther ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Gland ◽  
Coat Color ◽  
Phenotypic Expression ◽  
Expression Data ◽  
Rt Pcr ◽  
Specific Antibodies ◽  
Processed Form ◽  
Whole Transcriptome ◽  
Rat Tail

The premelanosome protein (PMEL) is important for fibril formation within melanosomes during vertebrate melanogenesis. Fibrils form a matrix for pigment deposition within pigmented tissues such as skin and hair. PMEL mutations are known to modulate eumelanic pigmentation in vertebrates. However, in bovines, PMEL mutations were also found to alter pheomelanic pigmentation resulting in coat color dilution. Furthermore, epistatic effects of a mutated PMEL allele were detected in the phenotypic expression of the bovine hair defect “rat-tail syndrome” (RTS) characterized by charcoal coat color and hair deformation. Reports about PMEL gene expression in non-pigmented tissues raised the hypothesis that there may be unknown functions of the PMEL protein beyond eumelanin deposition to PMEL fibrils. In our study, we analysed the PMEL protein expression in pigmented skin and non-pigmented bovine tissues (non-pigmented skin, thyroid gland, rumen, liver, kidney, and adrenal gland cortex). We found that a processed form of the bovine PMEL protein is expressed in pigmented as well as in non-pigmented tissues, which is in line with gene expression data from targeted RT-PCR and whole transcriptome RNAseq analysis. The PMEL protein is located in membranes and within the cytosol of epithelial cells. Based on our data from bovine tissues, we concluded that at least in cattle PMEL potentially has additional, yet unexplored functions, which might contribute to effects of PMEL mutations on pheomelanin coat color dilution and charcoal coat color in RTS animals. However, indication of PMEL protein in unpigmented cells and tissues will require further confirmation in the future, because there have been no confirmed reports before, which had detected bovine PMEL protein with specific antibodies either in pigmented or unpigmented tissue.

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