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Response of multiple genes to a chronic dose of corticosteroids in rat muscles


ABSTRACT: Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade Keywords: Time-Series We analyze the two time series profiles with the intent of seeking ways to use the two profiles in tandem for clustering. The acute profiles were generated by sacrificing animals following a single acute dose of MP [7]. The time points were: 0.25, 0.5, 0.75, 1, 2, 4, 5, 5.5, 6, 7, 8, 12, 18, 30, 48 and, 72 hours after dosing. The chronic profiles were generated by implanting Alzet mini-osmotic pumps with a constant flow rate [8, 9]. Animals were sacrificed at 6, 10, 13, 18, 24, 36, 48, 72, 96 and 168 hr following implantation.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Eric Hoffman 

PROVIDER: E-GEOD-5101 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens.

Almon Richard R RR   DuBois Debra C DC   Yao Zhenling Z   Hoffman Eric P EP   Ghimbovschi Svetlana S   Jusko William J WJ  

Physiological genomics 20070501 3


The transcriptional response of skeletal muscle to chronic corticosteroid exposure was examined over 168 h and compared with the response profiles observed following a single dose of corticosteroid. Male adrenalectomized Wistar rats were given a constant-rate infusion of 0.3 mg x kg(-1) x h(-1) methylprednisolone for up to 7 days via subcutaneously implanted minipumps. Four control and forty drug-treated animals were killed at ten different time points during infusion. Liver total RNAs were hybr  ...[more]

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