Anthracyclines selectively decrease alpha cardiac actin mRNA abundance in the rat heart.
Anthracyclines are widely used antineoplastic agents, but possess a major side effect of congestive cardiomyopathy. Previously we showed a selective effect of the most commonly used anthracycline, doxorubicin, on decreasing alpha-cardiac (alpha c) actin mRNA abundance in the rat heart. The current studies examined the effects of several anthracyclines (doxorubicin, daunorubicin, and epirubicin) to determine if doxorubicin's previously reported effect on alpha c actin mRNA abundance is: 1) a property shared by other cardiotoxic anthracyclines; 2) selective when compared with a wider spectrum of contractile protein and muscle-specific mRNAs; and 3) related to the characteristic ultrastructural alterations, such as loss of myofilaments, seen in anthracycline-induced cardiomyopathy. Results showed a major selective effect of doxorubicin, daunorubicin, and epirubicin on decreasing alpha c actin mRNA abundance when compared with other contractile protein and muscle-specific mRNAs. In addition, ultrastructural examination of myocardium showed contractile alterations, including loss of myofilaments. These results suggest that decreased expression of selected cardiac genes may relate to the molecular mechanism of clinical anthracycline-induced cardiomyopathy.
Papoian
T
T
Department of Pathology and Laboratory Medicine, UCLA School of Medicine.
Lewis
W
W
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000199:Actins / Q000235:genetics*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D004247:DNA / Q000032:analysis / Q000235:genetics; D003630:Daunorubicin / Q000009:adverse effects / Q000494:pharmacology; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D015251:Epirubicin / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D008854:Microscopy, Electron; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D015251:Epirubicin; D004317:Doxorubicin; D004247:DNA; D003630:Daunorubicin