Unknown,Transcriptomics,Genomics,Proteomics

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Corticosterone regulation of mRNAs and and corresponding RU486 antagonism in astrocytes in vitro

ABSTRACT: Analysis of mRNA gene expression changes mediated by natural glucocorticoid ligand corticosterone in mouse cortical primary astrocyte cultures; also, parallel analysis of RU486 (mifepristone) antagonism of corticosterone-mediated mRNA changes. Total RNA obtained from astrocyte cultures subjected to 2, 4, or 6 hours of (1) 100nM corticosterone alone, (2) 500nM RU486 alone, or (3) 100nM corticosterone + 500nM RU486 exposure compared to vehicle control astrocyte cultures.

ORGANISM(S): Mus musculus

SUBMITTER: Bradley Carter

PROVIDER: E-GEOD-39270 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Glucocorticoid treatment of astrocytes results in temporally dynamic transcriptome regulation and astrocyte-enriched mRNA changes in vitro.

Carter Bradley S BS Meng Fan F Thompson Robert C RC

Physiological genomics 20121030 24

While general effects of glucocorticoids are well established, the specific cellular mechanisms by which these hormones exert tissue-dependent effects continue to be elaborated. Diseases that demonstrate altered glucocorticoid signaling have been associated with alterations in astrocytes, yet relatively little is known about the effects of glucocorticoids upon this cell type. We have analyzed mRNA expression patterns following glucocorticoid treatment of mouse primary astrocyte cultures. Microar ...[more]

PMID: 23110767

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Project description:Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved. Objective: The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells) in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks. Materials and methods: The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge.Results: The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome [i.e., only 73/4171 (~1.8%) proteins displayed altered abundance]. By contrast, ~15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In-silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increased in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells. Conclusions: Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases.

Dataset Information

Corticosterone regulation of mRNAs and and corresponding RU486 antagonism in astrocytes in vitro

Publications

Glucocorticoid treatment of astrocytes results in temporally dynamic transcriptome regulation and astrocyte-enriched mRNA changes in vitro.

Similar Datasets

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