Actin isoform mRNA alterations induced by doxorubicin in cultured heart cells

Cultured rat myocardial cells (CMC) were incubated with adriamycin (ADR), an antineoplastic which causes dilated cardiomyopathy (COCM). CMC were exposed to 10(-7) M to 10(-5) M ADR for 24 hours, harvested, and CMC RNA was extracted. Extracted RNA underwent electrophoresis, transfer to nitrocellulose filters, and hybridization with radiolabeled cDNA probes which were specific for the actin isoforms (alpha, beta, and gamma) and isotypes (alpha sk = alpha skeletal; alpha c = alpha cardiac). RNA from CMC exposed to 10(-7) M ADR yielded a strong signal for mRNA coding for alpha c actin when probed with the isotype-specific cDNA. Hybridization signal was reduced in CMC extracts at 10(-6) M ADR. In CMC extracts at 10(-5) M ADR, the alpha c actin mRNA again hybridized. The cDNAs which were specific for beta and gamma actin isoforms yielded hybridization signals in extracts from CMC exposed to 10(-7) M and 10(-6) M ADR. These signals were reduced in extracts of CMC at 10(-5) M ADR. ADR's dose-related effect on the expression of alpha c actin in CMC is specific and suggests that ADR may have effects on regulation of CMC alpha c actin polypeptides and mRNA.