Profiling of Angiotensin II Rapid Response Genes in Human, Bovine, and Rat Adrenocortical Cells.
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ABSTRACT:
ORGANISM(S): Bos taurus Rattus norvegicus Homo sapiens
PROVIDER: GSE8442 | GEO | 2007/07/18
SECONDARY ACCESSION(S): PRJNA101513
REPOSITORIES: GEO
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Project description:Angiotensin II (Ang-II) regulates adrenal steroid production and gene transcription through several signaling pathways. Changes in gene transcription occur within minutes after Ang-II stimulation, causing an acute increase in aldosterone production and subsequent increase in the overall capacity to produce aldosterone. Our goal was to compare the Ang-II regulation of early gene expression and confirm the upregulation of selected genes using quantitative real-time RT-PCR (qPCR) across three species: human, bovine, and rat. Experiment Overall Design: Microarray analysis was performed using samples from control and Ang-II-(10 nM) treated (1 hour) cells from human adrenocortical tumor cell line H295-R, and primary adrenal glomerulosa cells from bovine and rat, applied respectively to human HG-133 + 2 , bovine, and rat 230-2 Affymetrix chips. qPCR was performed to confirm upregulation of selected genes using mRNA. Dye Swap was not used. Human samples (H295R) include 3 replicates of Basal (controls) and 3 repeats of Angiotensin II samples. Human H295R cells include also a group of cycloheximide (protein synthesis blocker) and angiontensin II + cycloheximide in order to check if the genes were direct targets of angiotensin II.
2008-11-06 | E-GEOD-8442 | biostudies-arrayexpress
Project description:The mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex. Experiment Overall Design: Freshly isolated rat adrenal cells were treated with Ang II (100 nM) or potassium (16 mM) for 2 h at 37C. Experiment Overall Design: Total RNA from three independent experiments were isolated, labeled and hybridized to whole genome high-density oligonucleotide microarrays (Affymetrix Rat Genome 230 2.0). Experiment Overall Design: 3 independent cell preparations. Experiment Overall Design: In each experiement there is one tube control, one Ang II (100 nM) and potassium (16 mM).
2008-10-18 | E-GEOD-8421 | biostudies-arrayexpress
Project description:H295R human adrenocortical cells treated with or without angiotensin II (100 nM) for 3 hr. Keywords = adrenal angiotensin aldosterone Keywords: parallel sample
2004-11-19 | GSE1030 | GEO
Project description:The mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex. Keywords: agent response
2008-06-29 | GSE8421 | GEO
Project description:H295R human adrenocortical cells treated with or without angiotensin II (100 nM) for 3 hr. Keywords = adrenal angiotensin aldosterone
2010-06-05 | E-GEOD-1030 | biostudies-arrayexpress
Project description:Transcriptome comparison of an aldosterone producing adenoma transcriptome and its adjacent zona glomerulosa. Both tissues are from the same individual, are differentiated for aldosterone production, but the adjacent zona glomerulosa produces no aldosterone by negative feedback. Keywords = aldosterone producing adenoma transcriptome Keywords: parallel sample
2005-10-11 | GSE2017 | GEO
Project description:Transcriptome comparison of an aldosterone producing adenoma transcriptome and its adjacent zona glomerulosa. Both tissues are from the same individual, are differentiated for aldosterone production, but the adjacent zona glomerulosa produces no aldosterone by negative feedback. Keywords = aldosterone producing adenoma transcriptome Keywords: parallel sample
2005-10-11 | E-GEOD-2017 | biostudies-arrayexpress
Project description:Primary aldosteronism (PA), a common cause of severe hypertension, features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) and 80 additional probands with unsolved early-onset PA. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of the identical p.Arg172Gln mutation; all relatives with early-onset PA carried the CLCN2 variant found in probands. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. In this data set, we examined RNA expression in H295R cells transfected with empty vector, WT and p.Arg172Gln CLCN2. Expression of CLCN2 led to increased expression of CYP11B2 and its upstream regulator NR4A2.
2017-12-08 | GSE107030 | GEO
Project description:The mineralocorticoid hormone, aldosterone, is secreted by the adrenal zona glomerulosa (ZG) in response to high plasma K+ and hypovolemia and promotes renal Na+ reabsorption and K+ secretion. Hence, the regulation of aldosterone secretion is critical for the control of ion homeostasis and blood pressure. While the kinase pathways regulating aldosterone production are well studied, little is known about the involved phosphatases. Using the human adrenocortical carcinoma cell line NCI-H295R, we found that the mRNA expression of the aldosterone synthase increases significantly within 6 hours after K+ exposure. This increase was inhibited in a dose-dependent manner by the calcineurin inhibitors tacrolimus and cyclosporine A. Calcineurin (Cn) is a serine-threonine-specific, Ca2+ and CaM-activated protein phosphatase essential for lymphocyte, neuronal and cardiac function. The physiologic role of Cn in the ZG cells and the molecular pathways by which Cn regulates the K+-stimulated secretion of aldosterone are unknown. To answer these questions, we stimulated NCI-H295R cells with K+ with or without Tacrolimus and studied the phosphorylation pattern of cytoplasmic proteins by phospho-proteomics. We generated a map of the changes in the Ser/Thr phosphorylation in adrenocortical cells upon stimulation with K+ and identified Cn-regulated phosphoproteins.
2023-05-25 | PXD027856 | Pride
Project description:ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), the phase 3 morbidity and mortality trial of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes in plasma levels of potassium, sodium, bicarbonate, and aldosterone. A key question after this trial is whether the failure of torcetrapib was a result of CETP inhibition or of some other pharmacology of the molecule. The direct effects of torcetrapib and related molecules on adrenal steroid production were assessed in cell culture using the H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines. Torcetrapib induced the synthesis of both aldosterone and cortisol in these two in vitro cell systems. Analysis of steroidogenic gene expression indicated that torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two enzymes in the last step of aldosterone and cortisol biosynthesis pathway, respectively. Transcription profiling indicated that torcetrapib and angiotensin II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone-induced steroid production is mainly mediated by two messengers, calcium and cAMP. An increase of intracellular calcium was observed after torcetrapib treatment, whereas cAMP was unchanged. Consistent with intracellular calcium being the key mediator of torcetrapib’s effect in adrenal cells, calcium channel blockers completely blocked torcetrapib-induced corticoid release and calcium increase. A series of compounds structurally related to torcetrapib as well as structurally distinct compounds were profiled. The results indicate that the pressor and adrenal effects observed with torcetrapib and related molecules are independent of CETP inhibition.
2009-05-02 | GSE15918 | GEO