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...

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Published in:Journal of molecular and cellular cardiology 2012-10, Vol.53 (4), p.475-486
Main Authors: Arantes, Lilian A.M, Aguiar, Carla J, Amaya, Maria Jimena, Figueiró, Núbia C.G, Andrade, Lídia M, Rocha-Resende, Cibele, Resende, Rodrigo R, Franchini, K.G, Guatimosim, Silvia, Leite, M. Fatima
Format: Article
Language:English
Subjects:
Animals
Calcineurin - metabolism
Calcium
Calcium - metabolism
Cardiomegaly - metabolism
Cardiomegaly - pathology
Cardiomyocyte
Cardiovascular
Cell Nucleus - metabolism
Cell Proliferation
Endothelin-1
Endothelin-1 - metabolism
Histone Deacetylases - metabolism
Hypertrophy
Inositol 1,4,5-Trisphosphate - metabolism
Inositol 1,4,5-Trisphosphate Receptors - metabolism
Insulin-Like Growth Factor I - metabolism
Insulin-like growth factor-1
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
NFATC Transcription Factors - metabolism
Nuclear IP3
Rats
Rats, Wistar
Signal Transduction
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Summary: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.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2012.06.017