Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of hearts from mice treated with aldosterone for different time duration to study the genetic mechanism of aldosterones direct adverse effects on the heart.

ABSTRACT: Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This experiment investigated of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration using oligonucleotide microarrays and compared to those of the control animals who underwent a sham injection. A novel software tool (CAGED) designed for analysis of temporal microarray experiments using a Bayesian approach was used to identify genes differentially expressed between the aldosterone-injected and control group. CAGED analysis identified twelve genes as having significant differences in their temporal profiles between aldosterone-injected and control groups. All of these genes exhibited a decrease in expression level 1-3 hours after aldosterone injection followed by a brief rebound and a return to baseline. These findings were validated by quantitative RT-PCR. The differentially expressed genes included phosphatases, regulators of steroid biosynthesis, inactivators of reactive oxygen species, and structural proteins. Several of these genes are known to functionally mediate biochemical phenomena previously observed to be triggered by aldosterone administration, such as phosphorylation of ERK1/2. These results provide the first description of cardiac genetic response to aldosterone and identify several potential mediators of known biochemical sequelae of aldosterone administration in the heart. Methods: Male C57BL6 mice were injected with aldosterone 10 mcg/kg (experimental group) or vehicle (control group) at time 0. Five animals were sacrificed at each of the following time points in each group: 0, 0.5, 1, 2, 3, 4, 5, and 12 hours from injection. Hearts were removed and total RNA extracted from the hearts of all five animals at each time point / experimental condition was pooled for gene expression analysis. Experiment Overall Design: Time series of effect of aldosterone on gene expression in the mouse heart

ORGANISM(S): Mus musculus

SUBMITTER: Alexander Turchin

PROVIDER: E-GEOD-3440 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Effect of acute aldosterone administration on gene expression profile in the heart.

Turchin Alexander A Guo Christine Z CZ Adler Gail K GK Ricchiuti Vincent V Kohane Isaac S IS Williams Gordon H GH

Endocrinology 20060406 7

Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This paper describes an investigation of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration ...[more]

PMID: 16601137

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Project description:Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This experiment investigated of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration using oligonucleotide microarrays and compared to those of the control animals who underwent a sham injection. A novel software tool (CAGED) designed for analysis of temporal microarray experiments using a Bayesian approach was used to identify genes differentially expressed between the aldosterone-injected and control group. CAGED analysis identified twelve genes as having significant differences in their temporal profiles between aldosterone-injected and control groups. All of these genes exhibited a decrease in expression level 1-3 hours after aldosterone injection followed by a brief rebound and a return to baseline. These findings were validated by quantitative RT-PCR. The differentially expressed genes included phosphatases, regulators of steroid biosynthesis, inactivators of reactive oxygen species, and structural proteins. Several of these genes are known to functionally mediate biochemical phenomena previously observed to be triggered by aldosterone administration, such as phosphorylation of ERK1/2. These results provide the first description of cardiac genetic response to aldosterone and identify several potential mediators of known biochemical sequelae of aldosterone administration in the heart. Methods: Male C57BL6 mice were injected with aldosterone 10 mcg/kg (experimental group) or vehicle (control group) at time 0. Five animals were sacrificed at each of the following time points in each group: 0, 0.5, 1, 2, 3, 4, 5, and 12 hours from injection. Hearts were removed and total RNA extracted from the hearts of all five animals at each time point / experimental condition was pooled for gene expression analysis. Keywords: time series

Project description:Scope: As a result of population ageing, the number of Alzheimer’s disease (AD) patients has rapidly increased. There are many hypothesises on the pathogenesis of AD, but its detailed molecular mechanism is still unknown, and so no effective preventive or therapeutic measures have been established. Some reports showed a decrease in levels of norepinephrine (NE) has been suspected to be involved in the decline of cognitive function in AD patients and NE concentrations were decreased in postmortem AD patient brains. Tyr-Trp was identified as being the most effective dipeptide in enhancing norepinephrine (NE) synthesis and metabolism. And Tyr-Trp treatment ameliorated the short-term memory dysfunction in AD model mice caused by amyloid beta (Aβ) 25-35. So, the purpose of this study was to investigate the preventive or/and protective effects of Tyr-Trp administration in AD model mice. Methods and results: ddY mice were fed normal diet. After 7 days of feeding, mice were divided into 3 groups (n=10 per group) as follows: the sham group, which received saline administration and distilled water injection; the Aβ group, which received saline administration and Aβ peptides 25–35 injection; and the Aβ+YW group, which received Tyr-Trp administration and Aβ peptides 25–35 injection. Tyr-Trp was orally administered Tyr-Trp (100 mg kg-1 day-1, twice a day), starting 7 days before Aβ peptides injection. The other groups received oral administration of saline (5 mL kg-1). After Aβ peptides injection or sham operation, each groups received every oral administration. DAN microarray showed that Tyrosine hydroxylase, dopa decarboxylase and dopamine receptor D2 mRNA expressions which were downregulated in Aβ group comparing with sham group were upregulated in Aβ+YW group comparing with Aβ group. In addition, quinoid dihydropteridine reductase mRNA expression which wasn’t changed in Aβ group comparing with sham group was upregulated in Aβ+YW group comparing with Aβ group. Conclusions: These results suggest that Tyr-Trp administration might ameliorate the short-term memory dysfunction in AD model mice because of enhancing norepinephrine (NE) synthesis and metabolism through metabolism of both Tyr and Trp.

Dataset Information

Transcription profiling of hearts from mice treated with aldosterone for different time duration to study the genetic mechanism of aldosterones direct adverse effects on the heart.

Publications

Effect of acute aldosterone administration on gene expression profile in the heart.

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