title: Alpha-actin synthesis changes in cultured cardiac myocytes: relationship to anthracycline structure.
abstract: Four anthracyclines (AAs) were examined comparatively to determine effects on actin isoform synthesis in vitro. Cultured cardiac myocytes (CMCs) were incubated for 24 hours with 35 microCi sulfur 35-labeled methionine and 10(-10) to 10(-5) mol/L doxorubicin hydrochloride (Adriamycin) (ADR), daunomycin (DM), 5-iminodaunorubicin IDR), or 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN). CMCs were harvested in buffered Triton X-100 and homogenized. Proteins in the extracts were fractionated by centrifugation. Equal protein quantities were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, to two-dimensional electrophoresis, and to autoradiography. AAs caused a dose-dependent decrease in radiolabeling of CMC proteins in Triton-soluble and -insoluble fractions of the extracts. ADR and DM (10(-6) mol/L each) and IDR (10(-5) mol/L) decreased radiolabeling of CMC polypeptides including alpha-actin. In polypeptides extracted in the Triton X-100-soluble pool, the effect on CMC alpha-actin synthesis was greater than the effect on beta- or gamma-actin. CMC alpha-actin synthesis was susceptible to ADR and to DM in a dose-dependent fashion. Contrastingly, alpha-actin radiolabeling was not altered by exposing CMCs to 10(-5) mol/L MRA-CN. Decreased sarcomeric actin isoform synthesis in vitro may reflect forms of subcellular damage in this model of anthracycline cardiomyopathy.
authors.affiliation: Department of Pathology, UCLA School of Medicine 90024.
authors.forename: W
authors.initials: W
authors.lastname: Lewis
authors.forename: N L
authors.initials: NL
authors.lastname: Perillo
authors.forename: B
authors.initials: B
authors.lastname: Gonzalez
mesh_terms: D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000032:analysis / Q000494:pharmacology*; D001345:Autoradiography; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009279:Naphthacenes / Q000032:analysis / Q000494:pharmacology; D051381:Rats
chemical_list: D000199:Actins; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes