| Literature DB >> 11889119 |
Haruhiro Toko1, 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.
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.Entities:
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Year: 2002 PMID： 11889119 DOI： 10.1074/jbc.M107669200
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157