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Recombinant TFAM attenuates pathological hypertrophy of cardiac myocytes via inhibiting NFAT signaling
Author(s) -
Fujino Takeo,
Ide Tomomi,
Hata Yuko,
Takehara Takako,
Yoshida Masayoshi,
Onitsuka Ken,
Tanaka Atsushi,
Takazaki Shinya,
Nishida Motohiro,
Kang Donchon,
Sunagawa Kenji
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.365.10
Background Mitochondrial transcription factor A (TFAM) is essential for mitochondrial DNA (mtDNA) transcription and replication. Overexpression of TFAM ameliorates cardiac remodeling after myocardial infarction. We hypothesized recombinant TFAM inhibits pathological hypertrophy and its intracellular signaling. Methods and Results We prepared recombinant human TFAM protein. TFAM, recruited into neonatal rat ventricular myocytes (NRVM) cytoplasm, dose‐dependently increased mtDNA copy number. Nuclear factor of activated T cell (NFAT) is a major regulator of pathological hypertrophy, and pretreatment with TFAM inhibited angiotensin II (AngII) and endothelin 1 (ET‐1)‐induced NFAT transcriptional activity (91±2% and 90±3% reduction, respectively). TFAM also suppressed AngII and ET‐1‐induced nuclear translocation of NFAT and NFAT‐dependent gene expression of brain natriuretic peptide. TFAM inhibited morphological hypertrophy of NRVM induced by AngII (1686±37 to 1167±20 μm 2 , p<0.01) and ET‐1 (1759±44 to 1206±21 μm 2 , p<0.01). Conclusions Pretreatment with TFAM increases mtDNA copy number, and attenuates AngII and ET‐1‐induced hypertrophy of cardiac myocytes via inhibiting NFAT signaling. Recombinant TFAM could be a novel therapy for cardiac hypertrophy and failure.