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Am J Physiol Heart Circ Physiol 276: H803-H814, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 3, H803-H814, March 1999

TAFII250, Egr-1, and D-type cyclin expression in mice and neonatal rat cardiomyocytes treated with doxorubicin

Nacéra Saadane1, Lesley Alpert2, and Lorraine E. Chalifour1,3

1 Lady Davis Institute for Medical Research and 2 Department of Pathology, Sir Mortimer B. Davis Jewish General Hospital, Montreal H3T 1E2; and 3 Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada H3A 1A3

Differential display identified that gene fragment HA220 homologous to the transcriptional activator factor II 250 (TAFII250) gene, or CCG1, was increased in hypertrophied rodent heart. To determine whether TAFII250 gene expression is modified after cardiac damage, we measured TAFII250 expression in vivo in mouse hearts after injection of the cardiotoxic agent doxorubicin (DXR) and in vitro in DXR-treated isolated rat neonatal cardiomyocytes. In vivo atrial natriuretic factor (ANF), beta -myosin heavy chain (beta -MHC), Egr-1, and TAFII250 expression increased with dose and time after a single DXR injection, but only ANF and beta -MHC expression were increased after multiple injections. After DXR treatment of neonatal cardiomyocytes we found decreased ANF, alpha -MHC, Egr-1, and TAFII250 expression. Expression of the TAFII250-regulated genes, the D-type cyclins, was increased after a single injection in adult mice and was decreased in DXR-treated cardiomyocytes. Thus expression of Erg-1, TAFII250, and the D-type cyclins is modulated after cardiotoxic damage in adult and neonatal heart.

cardiac damage; differential gene expression; transcriptional activator factor II 250; early growth response-1; cyclins D1, D2, and D3


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