title: Nuclear inositol 1,4,5-trisphosphate is a necessary and conserved signal for the induction of both pathological and physiological cardiomyocyte hypertrophy.
abstract: It is well established that inositol 1,4,5-trisphosphate (IP3) dependent Ca(2+) signaling plays a crucial role in cardiomyocyte hypertrophy. However, it is not yet known whether nuclear IP3 represents a Ca(2+) mobilizing pathway involved in this process. The goal of the current work was to investigate the specific role of nuclear IP3 in cardiomyocyte hypertrophic response. In this work, we used an adenovirus construct that selectively buffers IP3 in the nuclear region of neonatal cardiomyocytes. We showed for the first time that nuclear IP3 mediates endothelin-1 (ET-1) induced hypertrophy. We also found that both calcineurin (Cn)/nuclear factor of activated T Cells (NFAT) and histone deacetylase-5 (HDAC5) pathways require nuclear IP3 to mediate pathological cardiomyocyte growth. Additionally, we found that nuclear IP3 buffering inhibited insulin-like growth factor-1 (IGF-1) induced hypertrophy and prevented reexpression of fetal gene program. Together, these results demonstrated that nuclear IP3 is an essential and a conserved signal for both pathological and physiological forms of cardiomyocyte hypertrophy.
authors: Department of Physiology and Biophysics, Federal University of Minas Gerais, Av Antônio Carlos, 6627-Campus Pampulha 31270-901 Belo Horizonte, MG, Brazil. lili.muniz.arantes@gmail.com
authors: Lilian A M
authors: LA
authors: Arantes
authors: Carla J
authors: CJ
authors: Aguiar
authors: Maria Jimena
authors: MJ
authors: Amaya
authors: Núbia C G
authors: NC
authors: Figueiró
authors: Lídia M
authors: LM
authors: Andrade
authors: Cibele
authors: C
authors: Rocha-Resende
authors: Rodrigo R
authors: RR
authors: Resende
authors: K G
authors: KG
authors: Franchini
authors: Silvia
authors: S
authors: Guatimosim
authors: M Fatima
authors: MF
authors: Leite
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D019332:Endothelin-1; D053496:Inositol 1,4,5-Trisphosphate Receptors; D050778:NFATC Transcription Factors; D007334:Insulin-Like Growth Factor I; D015544:Inositol 1,4,5-Trisphosphate; D019703:Calcineurin; C498619:Hdac5 protein, rat; D006655:Histone Deacetylases; D002118:Calcium