Recombinant mitochondrial transcription factor A protein inhibits nuclear factor of activated T cells signaling and attenuates pathological hypertrophy of cardiac myocytes.
The overexpression of mitochondrial transcription factor A (TFAM) attenuates the decrease in mtDNA copy number after myocardial infarction, ameliorates pathological hypertrophy, and markedly improves survival. However, non-transgenic strategy to increase mtDNA for the treatment of pathological hypertrophy remains unknown. We produced recombinant human TFAM protein (rhTFAM). rhTFAM rapidly entered into mitochondria of cultured cardiac myocytes. rhTFAM increased mtDNA and abolished the activation of nuclear factor of activated T cells (NFAT), which is well known to activate pathological hypertrophy. rhTFAM attenuated subsequent morphological hypertrophy of myocytes as well. rhTFAM would be an attractive molecule in attenuating cardiac pathological hypertrophy.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Takeo
T
Fujino
Tomomi
T
Ide
Masayoshi
M
Yoshida
Ken
K
Onitsuka
Atsushi
A
Tanaka
Yuko
Y
Hata
Motohiro
M
Nishida
Takako
T
Takehara
Takaaki
T
Kanemaru
Naoyuki
N
Kitajima
Shinya
S
Takazaki
Hitoshi
H
Kurose
Dongchon
D
Kang
Kenji
K
Sunagawa
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000503:physiopathology*; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D050778:NFATC Transcription Factors; D011994:Recombinant Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A