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Type: Artigo de periódico
Title: A role for focal adhesion kinase in cardiac mitochondrial biogenesis induced by mechanical stress
Author: Tornatore, TF
Costa, AP
Clemente, CFMZ
Judice, C
Rocco, SA
Calegari, VC
Cardoso, L
Cardoso, AC
Goncalves, A
Franchini, KG
Abstract: Tornatore TF, Dalla Costa AP, Clemente CF, Judice C, Rocco SA, Calegari VC, Cardoso L, Cardoso AC, Gon alves Jr A, Franchini KG. A role for focal adhesion kinase in cardiac mitochondrial biogenesis induced by mechanical stress. Am J Physiol Heart Circ Physiol 300: H902-H912, 2011. First published December 10, 2010; doi:10.1152/ajpheart.00319.2010.-We studied the implication of focal adhesion kinase (FAK) in cardiac mitochondrial biogenesis induced by mechanical stress. Prolonged stretching (2-12 h) of neonatal rat ventricular myocytes (NRVM) upregulated the main components of mitochondrial transcription cascade [peroxisome proliferator-activated receptor coactivator-1 (PGC-1 alpha), nuclear respiratory factor (NRF-1), and mitochondrial transcription factor A]. Concomitantly, prolonged stretching enhanced mitochondrial biogenesis [copy number of mitochondrial DNA (mtDNA), content of the subunit IV of cytochrome oxidase, and mitochondrial staining-green fluorescence intensity of Mitotracker green] and induced the hypertrophic growth (cell size and atrial natriuretic peptide transcripts) of NRVM. Furthermore, the stretching of NRVM enhanced phosphorylation, nuclear localization, and association of FAK with PGC-1 alpha. Recombinant FAK COOH-terminal, but not the NH(2)-terminal or kinase domain, precipitated PGC-1 alpha from nuclear extracts of NRVM. Depletion of FAK by RNA interference suppressed the upregulation of PGC-1 alpha and NRF-1 and markedly attenuated the enhanced mitochondrial biogenesis and hypertrophic growth of stretched NRVM. In the context of energy metabolism, FAK depletion became manifest by a reduction of ATP levels in stretched NRVM. Complementary studies in adult mice left ventricle demonstrated that pressure overload upregulated PGC-1 alpha, NRF-1, and mtDNA. In vivo FAK silencing transiently attenuated the upregulation of PGC-1 alpha, NRF-1, and mtDNA, as well as the left ventricular hypertrophy induced by pressure overload. In conclusion, activation of FAK signaling seems to be important for conferring enhanced mitochondrial biogenesis coupled to the hypertrophic growth of cardiomyocytes in response to mechanical stress, via control of mitochondrial transcription cascade.
Subject: mechanical stress
signal transduction
Country: EUA
Editor: Amer Physiological Soc
Citation: American Journal Of Physiology-heart And Circulatory Physiology. Amer Physiological Soc, v. 300, n. 3, n. H902, n. H912, 2011.
Rights: embargo
Identifier DOI: 10.1152/ajpheart.00319.2010
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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