Transcription profiling of rat skeletal muscle treated with cerivastatin
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ABSTRACT: Adverse effects of statins include skeletal muscle toxicity; Type II glycolytic fibers are more senstive to statin damage; exercise exacerbates statin muscle degeneration. We used a well-characterized rat model of statin-induced muscle degeneration, at which 1.0 mg/kg/day (high dose) cerivastatin produces mild to moderate histological degeneration. We used microarrays to detail the global programme of gene expression underlying cerivastatin effects on rat gastrocnemius and soleus muscles, as well as the effect of cerivastatin combined with treadmill exercise. We identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: We treated female SD rats with vehicle or 3 doses of cerivastatin (0.1, 0.5, 1.0 mg/kg/day) for 14 days, plus or minus 5 days/week of exercise on treadmills (20 min/day at 20 m/min). Gastrocnemius and soleus muscle samples were harvested for RNA extraction and hybridization on Affymetrix microarrays. A total of 12 samples were analyzed with 3-4 biological replicates per sample. Our goals were to determine 1) the effect of cerivastatin; 2) the effect of exercise combined with cerivastatin; 3) an explanation for the muscle fiber type sensitivity to statins. Since all doses of cerivastatin had no effect on soleus muscle (PubMed ID: 16141437), we analysed samples from soleus from control and high dose groups only.
ORGANISM(S): Rattus norvegicus
SUBMITTER: Jennifer Seachrist
PROVIDER: E-GEOD-4418 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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