title: Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart.
abstract: Csx/Nkx2-5, which is essential for cardiac development of the embryo, is abundantly expressed in the adult heart. We here examined the role of Csx/Nkx2-5 in the adult heart using two kinds of transgenic mice. Transgenic mice that overexpress a dominant negative mutant of Csx/Nkx2-5 (DN-TG mice) showed degeneration of cardiac myocytes and impairment of cardiac function. Doxorubicin induced more marked cardiac dysfunction in DN-TG mice and less in transgenic mice that overexpress wild type Csx/Nkx2-5 (WT-TG mice) compared with non-transgenic mice. Doxorubicin induced cardiomyocyte apoptosis, and the number of apoptotic cardiomyocytes was high in the order of DN-TG mice, non-transgenic mice, and WT-TG mice. Overexpression of the dominant negative mutant of Csx/Nkx2-5 induced apoptosis in cultured cardiomyocytes, while expression of wild type Csx/Nkx2-5 protected cardiomyocytes from doxorubicin-induced apoptotic death. These results suggest that Csx/Nkx2-5 plays a critical role in maintaining highly differentiated cardiac phenotype and in protecting the heart from stresses including doxorubicin.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.forename: Eiki
authors.initials: E
authors.lastname: Takimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shiojima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hiroi
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Toru
authors.initials: T
authors.lastname: Oka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.forename: Miho
authors.initials: M
authors.lastname: Mizukami
authors.forename: Masaya
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Terasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takano
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D017124:Conserved Sequence; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007930:Leucine; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009206:Myocardium / Q000166:cytology*; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D007930:Leucine