title: Overexpression of Nd1, a novel Kelch family protein, in the heart of transgenic mice protects against doxorubicin-induced cardiomyopathy.
abstract: Doxorubicin is one of the most effective drugs available for cancer chemotherapy. However, the clinical use of doxorubicin has been greatly limited because of severe side effects on cardiomyocytes. Since Nd1-L, a novel actin-binding protein, is expressed most abundantly in the heart of adult mice, we examined a role of Nd1-L in doxorubicin-induced cardiomyopathy. When doxorubicin (5 mg/kg x 4 times) was injected into adult mice at a 3-day-interval, approximately 50% of injected mice died within 4 weeks of the first injection. Nd1-L mRNA expression in the heart decreased within 3 weeks after the first injection and many cardiomyocytes of injected mice died by apoptosis. Overexpression of Nd1-L in the heart of transgenic mice protected the cardiomyocytes from apoptosis and improved survival rate after doxorubicin injection. Furthermore, activation of Erk1/2 was observed in cultured cells overexpressing Nd1-L. Thus, Nd1-L plays a critical role in protecting the heart from doxorubicin-induced cardiomyopathy.
authors.affiliation: Department of Developmental Genetics (H2), Graduate school of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsudo
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Takamori
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.forename: Saori
authors.initials: S
authors.lastname: Nishio
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sasagawa
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: D000903:Antibiotics, Antineoplastic; D047908:Intracellular Signaling Peptides and Proteins; C432129:Nd1 protein, mouse; D011506:Proteins; D004317:Doxorubicin