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Mouse cardiac tissue, polysomes and monosomes: Vehicle treated control vs. 15mg/kg doxorubicin


ABSTRACT: Translational profiling of mouse cardiac tissue treated with 15mg/kg doxorubicin in 10 ml/kg saline over an acute time course (0.5-120 hours) compared to time matched control animals treated with 10ml/kg saline. Two colour microarrays with time matched controls vs 15mg/kg doxorubicin cardiac tissue. Before microarray analysis, RNA is separated on a sucrose density gradient into those mRNAs activity undergoing translation (polysomes) and those not (monosomes) with control monosomes and treated monosomes on one set of arrays, and polysome control and polysome treated on another set of microarrays. Thealized Log2 of the monosomes was subtracted from the respective Log2 of the polysomes (on Series record). Time points studied were 0.5, 1, 2, 12, 24 and 120 hours following dosing, biological replicates n=3 independent animals at each time point, technical replicates (reverse labelling) n<1. One array printed onto two slides (A and B), one replicate per array.

ORGANISM(S): Mus musculus

SUBMITTER: Amy Pointon 

PROVIDER: E-GEOD-17823 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Doxorubicin in vivo rapidly alters expression and translation of myocardial electron transport chain genes, leads to ATP loss and caspase 3 activation.

Pointon Amy V AV   Walker Tracy M TM   Phillips Kate M KM   Luo Jinli J   Riley Joan J   Zhang Shu-Dong SD   Parry Joel D JD   Lyon Jonathan J JJ   Marczylo Emma L EL   Gant Timothy W TW  

PloS one 20100915 9


<h4>Background</h4>Doxorubicin is one of the most effective anti-cancer drugs but its use is limited by cumulative cardiotoxicity that restricts lifetime dose. Redox damage is one of the most accepted mechanisms of toxicity, but not fully substantiated. Moreover doxorubicin is not an efficient redox cycling compound due to its low redox potential. Here we used genomic and chemical systems approaches in vivo to investigate the mechanisms of doxorubicin cardiotoxicity, and specifically test the hy  ...[more]

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