AIMS: The aim of the present study was to determine the function and the role of the scaffold protein AKAP121, tethering cAMP dependent protein kinase A to the outer wall of mitochondria, in neonatal ventricular myocytes and the heart. METHODS AND RESULTS: Competitive peptides displacing AKAP121 from mitochondria in the tissue and in the cells were used to investigate the role of AKAP121 in mitochondrial function, reactive oxygen species (ROS) generation, and cell survival. Displacement of AKAP121 from mitochondria by synthetic peptides triggers the death program in cardiomyocytes. Under pathological conditions in vivo, in a rat model of cardiac hypertrophy induced by ascending aorta banding, the levels of AKAP121 are significantly down-regulated. Disappearance of AKAP121 is associated with mitochondrial dysfunction, high oxidative stress, and apoptosis. In vivo delocalization of AKAP121 by competitive peptides replicates some of the molecular signatures induced by pressure overload: mitochondrial dysfunction, increased mitochondrial ROS, and apoptosis. CONCLUSION: These data suggest that AKAP121 regulates the response to stress in cardiomyocytes, and therefore AKAP121 downregulation might represent an important event contributing to the development of cardiac dysfunction.

AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress / Perrino, Cinzia; Feliciello, Antonio; Schiattarella, GABRIELE GIACOMO; Esposito, Giovanni; Guerriero, Rosalia; Zaccaro, Laura; Del Gatto, A.; Saviano, M.; Garbi, Corrado; Carangi, R.; Di Lorenzo, E.; Donato, G.; Indolfi, Ciro; Avvedimento, VITTORIO ENRICO; Chiariello, Massimo. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - STAMPA. - 88:1(2010), pp. 101-110. [10.1093/cvr/cvq155]

AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress.

PERRINO, CINZIA;FELICIELLO, ANTONIO;SCHIATTARELLA, GABRIELE GIACOMO;ESPOSITO, GIOVANNI;GUERRIERO, ROSALIA;ZACCARO, LAURA;GARBI, CORRADO;INDOLFI, CIRO;AVVEDIMENTO, VITTORIO ENRICO;CHIARIELLO, MASSIMO
2010

Abstract

AIMS: The aim of the present study was to determine the function and the role of the scaffold protein AKAP121, tethering cAMP dependent protein kinase A to the outer wall of mitochondria, in neonatal ventricular myocytes and the heart. METHODS AND RESULTS: Competitive peptides displacing AKAP121 from mitochondria in the tissue and in the cells were used to investigate the role of AKAP121 in mitochondrial function, reactive oxygen species (ROS) generation, and cell survival. Displacement of AKAP121 from mitochondria by synthetic peptides triggers the death program in cardiomyocytes. Under pathological conditions in vivo, in a rat model of cardiac hypertrophy induced by ascending aorta banding, the levels of AKAP121 are significantly down-regulated. Disappearance of AKAP121 is associated with mitochondrial dysfunction, high oxidative stress, and apoptosis. In vivo delocalization of AKAP121 by competitive peptides replicates some of the molecular signatures induced by pressure overload: mitochondrial dysfunction, increased mitochondrial ROS, and apoptosis. CONCLUSION: These data suggest that AKAP121 regulates the response to stress in cardiomyocytes, and therefore AKAP121 downregulation might represent an important event contributing to the development of cardiac dysfunction.
2010
AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress / Perrino, Cinzia; Feliciello, Antonio; Schiattarella, GABRIELE GIACOMO; Esposito, Giovanni; Guerriero, Rosalia; Zaccaro, Laura; Del Gatto, A.; Saviano, M.; Garbi, Corrado; Carangi, R.; Di Lorenzo, E.; Donato, G.; Indolfi, Ciro; Avvedimento, VITTORIO ENRICO; Chiariello, Massimo. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - STAMPA. - 88:1(2010), pp. 101-110. [10.1093/cvr/cvq155]
File in questo prodotto:
File Dimensione Formato  
Cardiovasc Res 2010.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Accesso privato/ristretto
Dimensione 501.78 kB
Formato Adobe PDF
501.78 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/369162
Citazioni
  • ???jsp.display-item.citation.pmc??? 40
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 58
social impact