AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress(430 views) Perrino C, Feliciello A, Schiattarella GG, Esposito G, Guerriero R, Zaccaro L, Del Gatto A, Saviano M, Garbi C, Carangi R, Di Lorenzo E, Donato G, Indolfi C, Avvedimento VE, Chiariello M
Cardiovascular Research (ISSN: 0008-6363), 2010 Oct; 88(1): 101-110.
Keywords: Heart Failure, Mitochondria, Oxygen Radicals, Protein Kinase A, Cyclic Amp, Cyclic Amp Dependent Protein Kinase Anchoring Protein, Protein Akap121, Reactive Oxygen Metabolite, Scaffold Protein, Synthetic Peptide, Unclassified Drug, Animal Experiment, Animal Model, Apoptosis, Article, Cell Death, Cell Survival, Disorders Of Mitochondrial Functions, Down Regulation, Heart Left Ventricle Hypertrophy, Heart Muscle Cell, Heart Ventricle Hypertrophy, In Vivo Study, Mitochondrial Membrane, Nonhuman, Oxidative Stress, Priority Journal, A Kinase Anchor Proteins, Newborn, Binding, Competitive, Cultured, Disease Models, Down-Regulation, Left Ventricular, Inbred C57bl, Myocytes, Cardiac, Smooth Muscle, Wistar, Second Messenger Systems,
Affiliations: *** IBB - CNR ***
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy
Istituto Neurologico Mediterraneo, Pozzilli (IS), Italy
Department of Molecular and Cellular Pathology, Federico II University, Via Pansini 5, Naples 80131, Italy
Istituto di Biostrutture e Bioimmagini (CNR), Naples, Italy
Magna Graecia University, Catanzaro, Italy
Rockman, H.A., Koch, W.J., Lefkowitz, R.J., Seven-transmembrane-spanning receptors and heart function (2002) Nature, 415, pp. 206-212
Zakhary, D.R., Moravec, C.S., Bond, M., Regulation of PKA binding to AKAPs in the heart: Alterations in human heart failure (2000) Circulation, 101, pp. 1459-1464
Mauban, J.R., O'Donnell, M., Warrier, S., Manni, S., Bond, M., AKAP-scaffolding proteins and regulation of cardiac physiology (2009) Physiology (Bethesda), 24, pp. 78-87
Dodge-Kafka, K.L., Langeberg, L., Scott, J.D., Compartmentation of cyclic nucleotide signaling in the heart: The role of A-kinase anchoring proteins (2006) Circ Res, 98, pp. 993-1001
Indolfi, C., Stabile, E., Coppola, C., Gallo, A., Perrino, C., Allevato, G., Membrane-bound protein kinase A inhibits smooth muscle cell proliferation in vitro and in vivo by amplifying cAMP-protein kinase A signals (2001) Circ Res, 88, pp. 319-324
Carnegie, G.K., Soughayer, J., Smith, F.D., Pedroja, B.S., Zhang, F., Diviani, D., AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway (2008) Mol Cell, 32, pp. 169-179
Pare, G.C., Bauman, A.L., McHenry, M., Michel, J.J., Dodge-Kafka, K.L., Kapiloff, M.S., The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by adrenergic receptor signaling (2005) J Cell Sci, 118, pp. 5637-5646
De Windt, L.J., Lim, H.W., Bueno, O.F., Liang, Q., Delling, U., Braz, J.C., Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo (2001) Proc Natl Acad Sci USA, 98, pp. 3322-3327
Carlucci, A., Lignitto, L., Feliciello, A., Control of mitochondria dynamics and oxidative metabolism by cAMP, AKAPs and the proteasome (2008) Trends Cell Biol, 18, pp. 604-613
Feliciello, A., Rubin, C.S., Avvedimento, E.V., Gottesman, M.E., Expression of a kinase anchor protein 121 is regulated by hormones in thyroid and testicular germ cells (1998) J Biol Chem, 273, pp. 23361-23366
Cardone, L., Carlucci, A., Affaitati, A., Livigni, A., Decristofaro, T., Garbi, C., Mitochon-drial AKAP121 binds and targets protein tyrosine phosphatase D1, a novel positive regulator of src signaling (2004) Mol Cell Biol, 24, pp. 4613-4626
Livigni, A., Scorziello, A., Agnese, S., Adornetto, A., Carlucci, A., Garbi, C., Mitochon-drial AKAP121 links cAMP and src signaling to oxidative metabolism (2006) Mol Biol Cell, 17, pp. 263-271
Scholten, A., Van Veen, T.A., Vos, M.A., Heck, A.J., Diversity of cAMP-dependent protein kinase isoforms and their anchoring proteins in mouse ventricular tissue (2007) J Proteome Res, 6, pp. 1705-1717
Abrenica, B., Alshaaban, M., Czubryt, M.P., The A-kinase anchor protein AKAP121 is a negative regulator of cardiomyocyte hypertrophy (2009) J Mol Cell Cardiol, 46, pp. 674-681
Indolfi, C., Di Lorenzo, E., Perrino, C., Stingone, A.M., Curcio, A., Torella, D., Hydro-xymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation (2002) Circulation, 106, pp. 2118-2124
Feliciello, A., Gottesman, M.E., Avvedimento, E.V., CAMP-PKA signaling to the mitochondria: Protein scaffolds, mRNA and phosphatases (2005) Cell Signal, 17, pp. 279-287
De Capua, A., Del Gatto, A., Zaccaro, L., Saviano, G., Carlucci, A., Livigni, A., A synthetic peptide reproducing the mitochondrial targeting motif of AKAP121: A confor-mational study (2004) Biopolymers, 76, pp. 459-466
Baschong, W., Suetterlin, R., Laeng, R.H., Control of autofluorescence of archival formaldehyde-fixed, paraffin-embedded tissue in confocal laser scanning microscopy (CLSM) (2001) J Histochem Cytochem, 49, pp. 1565-1572
Carlucci, A., Adornetto, A., Scorziello, A., Viggiano, D., Foca, M., Cuomo, O., Proteol-ysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia (2008) EMBO J, 27, pp. 1073-1084
Takimoto, E., Kass, D.A., Role of oxidative stress in cardiac hypertrophy and remodeling (2007) Hypertension, 49, pp. 241-248
Papa, S., Scacco, S., Sardanelli, A.M., Petruzzella, V., Vergari, R., Signorile, A., Complex i and the cAMP cascade in human physiopathology (2002) Biosci Rep, 22, pp. 3-16
Harada, H., Becknell, B., Wilm, M., Mann, M., Huang, L.J., Taylor, S.S., Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A (1999) Mol Cell, 3, pp. 413-422
Rockman, H. A., Koch, W. J., Lefkowitz, R. J., Seven-transmembrane-spanning receptors and heart function (2002) Nature, 415, pp. 206-212
Zakhary, D. R., Moravec, C. S., Bond, M., Regulation of PKA binding to AKAPs in the heart: Alterations in human heart failure (2000) Circulation, 101, pp. 1459-1464
Mauban, J. R., O'Donnell, M., Warrier, S., Manni, S., Bond, M., AKAP-scaffolding proteins and regulation of cardiac physiology (2009) Physiology (Bethesda), 24, pp. 78-87
Dodge-Kafka, K. L., Langeberg, L., Scott, J. D., Compartmentation of cyclic nucleotide signaling in the heart: The role of A-kinase anchoring proteins (2006) Circ Res, 98, pp. 993-1001
Carnegie, G. K., Soughayer, J., Smith, F. D., Pedroja, B. S., Zhang, F., Diviani, D., AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway (2008) Mol Cell, 32, pp. 169-179
Pare, G. C., Bauman, A. L., McHenry, M., Michel, J. J., Dodge-Kafka, K. L., Kapiloff, M. S., The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by adrenergic receptor signaling (2005) J Cell Sci, 118, pp. 5637-5646
De Windt, L. J., Lim, H. W., Bueno, O. F., Liang, Q., Delling, U., Braz, J. C., Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo (2001) Proc Natl Acad Sci USA, 98, pp. 3322-3327
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. 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. 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.
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