Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart

  • J Biol Chem. 2002 Jul 5;277(27):24735-43. doi: 10.1074/jbc.M107669200.
Haruhiro Toko  1 ,  Weidong Zhu ,  Eiki Takimoto ,  Ichiro Shiojima ,  Yukio Hiroi ,  Yunzeng Zou ,  Toru Oka ,  Hiroshi Akazawa ,  Miho Mizukami ,  Masaya Sakamoto ,  Fumio Terasaki ,  Yasushi Kitaura ,  Hiroyuki Takano ,  Toshio Nagai ,  Ryozo Nagai ,  Issei Komuro
Affiliations
  • 1. Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
PMID: 11889119 DOI: 10.1074/jbc.M107669200
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.