Abstract
The ubiquitous sodium–calcium exchanger isoform 1 (NCX1) is a bidirectional transporter that plays a relevant role under physiological and pathophysiological conditions including brain ischemia by regulating intraneuronal Ca2+ and Na+ homeostasis. Although changes in ncx1 protein and transcript expression have been detected during stroke, its transcriptional regulation is still largely unexplored. Here, we reviewed our recent findings on several transcription factors including cAMP response element-binding protein (CREB), nuclear factor kappa B (NF-κB), and hypoxia-inducible factor-1 (HIF-1) in the control of the ncx1 gene expression in neuronal cells.
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References
L. Annunziato, G. Pignataro, G.F. Di Renzo, Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol. Rev. 56, 633–654 (2004)
L. Annunziato, G. Pignataro, F. Boscia, R. Sirabella, L. Formisano, M. Saggese, O. Cuomo, R. Gala, A. Secondo, D. Viggiano, P. Molinaro, V. Valsecchi, A. Tortiglione, A. Adornetto, A. Scorziello, M. Cataldi, GF. Di Renzo
L. Annunziato, P. Molinaro, A. Secondo, A. Panaccione, A. Scorziello, G. Pignataro, O. Cuomo, R. Sirabella, F. Boscia, A. Spinali, G. Di Renzo, The Na+/Ca2+ exchanger: a target for therapeutic intervention in cerebral ischemia, in New Strategies in Stroke Intervention, ed. by L. Annunziato (Springer, Totowa, 2009), pp. 65–87
H. Autio, K. Matlik, T. Rantamaki, L. Lindemann, M.C. Hoener, M. Chao, U. Arumae, E. Castren, Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus. Neuropharmacology 61, 1291–1296 (2011)
K.V. Barnes, G. Cheng, M.M. Dawson, D.R. Menick, Cloning of cardiac, kidney, and brain promoters of the feline NCX1 gene. J. Biol. Chem. 272, 11510–11517 (1997)
M. Bergeron, A.Y. Yu, K.E. Solway, G.L. Semenza, F.R. Sharp, Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur. J. Neurosci. 11, 4159–4170 (1999)
F. Boscia, R. Gala, G. Pignataro, A. de Bartolomeis, M. Cicale, A. Ambesi-Impiombato, G. Di Renzo, L. Annunziato, Permanent focal brain ischemia induces isoform-dependent changes in the pattern of Na+/Ca2+ exchanger gene expression in the ischemic core, periinfarct area, and intact brain regions. J. Cereb. Blood Flow Metab. 26, 502–517 (2006)
R.K. Bruick, Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia-inducible transcription factor. Genes Dev. 17, 2614–2623 (2003)
J.C. Chavez, J.C. LaManna, Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1. J. Neurosci. 22, 8922–8931 (2002)
G. Cheng, T.P. Hagen, M.L. Dawson, K.V. Barnes, D.R. Menick, The role of GATA, CArG, E-box, and a novel element in the regulation of cardiac expression of the Na+-Ca2+ exchanger gene. J. Biol. Chem. 274, 12819–12826 (1999)
S.T. Crews, Control of cell lineage-specific development and transcription by bHLH-PAS proteins. Genes Dev. 12, 607–620 (1998)
D. De Cesare, G.M. Fimia, P. Sassone-Corsi, Signaling routes to CREM and CREB: plasticity in transcriptional activation. Trends Biochem. Sci. 24, 281–285 (1999)
L. Formisano, M. Saggese, A. Secondo, R. Sirabella, P. Vito, V. Valsecchi, P. Molinaro, G. Di Renzo, L. Annunziato, The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel additional targets for the prosurvival action of Akt/protein kinase B pathway. Mol. Pharmacol. 73, 727–737 (2008)
K. Fukunaga, T. Kawano, Akt is a molecular target for signal transduction therapy in brain ischemic insult. J. Pharmacol. Sci. 92, 317–327 (2003)
N. Gabellini, S. Bortoluzzi, G.A. Danieli, E. Carafoli, The gene promoter of human Na+/Ca2+ exchanger isoform 3 (SLC8A3) is controlled by cAMP and calcium. Ann. N. Y. Acad. Sci. 976, 282–284 (2002)
N. Gabellini, S. Bortoluzzi, G.A. Danieli, E. Carafoli, Control of the Na+/Ca2+ exchanger 3 promoter by cyclic adenosine monophosphate and Ca2+ in differentiating neurons. J. Neurochem. 84, 282–293 (2003)
G.T. Gibney, J.H. Zhang, R.M. Douglas, G.G. Haddad, Y. Xia, Na+/Ca2+ exchanger expression in the developing rat cortex. Neuroscience 112, 65–73 (2002)
K.L. Golden, Q.I. Fan, B. Chen, J. Ren, J. O’Connor, J.D. Marsh, Adrenergic stimulation regulates Na+/Ca2+exchanger expression in rat cardiac myocytes. J. Mol. Cell. Cardiol. 32, 611–620 (2000)
R. Gomez-Villafuertes, B. Torres, J. Barrio, M. Savignac, N. Gabellini, F. Rizzato, B. Pintado, A. Gutierrez-Adan, B. Mellstrom, E. Carafoli, J.R. Naranjo, Downstream regulatory element antagonist modulator regulates Ca2+ homeostasis and viability in cerebellar neurons. J. Neurosci. 25, 10822–10830 (2005)
M.S. Hayden, S. Ghosh, Shared principles in NF-kappaB signaling. Cell 132, 344–362 (2008)
B.H. Jiang, E. Rue, G.L. Wang, R. Roe, G.L. Semenza, Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J. Biol. Chem. 271, 17771–17778 (1996)
P.J. Kallio, I. Pongratz, K. Gradin, J. McGuire, L. Poellinger, Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and conformational change by recruitment of the ARNT transcription factor. Proc. Natl. Acad. Sci. U. S. A. 94, 5667–5672 (1997)
S.L. Lee, A.S. Yu, J. Lytton, Tissue-specific expression of Na+-Ca2+ exchanger isoforms. J. Biol. Chem. 269, 14849–14852 (1994)
A.P. Levy, N.S. Levy, S. Wegner, M.A. Goldberg, Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J. Biol. Chem. 270, 13333–13340 (1995)
Z. Li, S. Matsuoka, L.V. Hryshko, D.A. Nicoll, M.M. Bersohn, E.P. Burke, R.P. Lifton, K.D. Philipson, Cloning of the NCX2 isoform of the plasma membrane Na+-Ca2+ exchanger. J. Biol. Chem. 269, 17434–17439 (1994)
L. Li, D. Guerini, E. Carafoli, Calcineurin controls the transcription of Na+/Ca2+ exchanger isoforms in developing cerebellar neurons. J. Biol. Chem. 275, 20903–20910 (2000)
L.L. Li, L.N. Sun, H.Y. Zhou, Z.B. Li, X.L. Wang, Selective alteration of expression of Na+/Ca2+ exchanger isoforms after transient focal cerebral ischemia in rats. Neurosci. Lett. 404, 249–253 (2006)
J. Lu, X.Y. Tong, X.L. Wang, Altered gene expression of Na+/Ca2+ exchanger isoforms NCX1, NCX2 and NCX3 in chronic ischemic rat brain. Neurosci. Lett. 332, 21–24 (2002)
C. Matrone, G. Pignataro, P. Molinaro, C. Irace, A. Scorziello, G.F. Di Renzo, L. Annunziato, HIF-1alpha reveals a binding activity to the promoter of iNOS gene after permanent middle cerebral artery occlusion. J. Neurochem. 90, 368–378 (2004)
J.G. Muller, J.T. Thompson, A.M. Edmonson, M.S. Rackley, H. Kasahara, S. Izumo, T.C. McQuinn, D.R. Menick, T.X. O’Brien, Differential regulation of the cardiac sodium calcium exchanger promoter in adult and neonatal cardiomyocytes by Nkx2.5 and serum response factor. J. Mol. Cell. Cardiol. 34, 807–821 (2002)
S.B. Nicholas, K.D. Philipson, Cardiac expression of the Na+/Ca2+ exchanger NCX1 is GATA factor dependent. Am. J. Physiol. 277, H324–H330 (1999)
S.B. Nicholas, W. Yang, S.L. Lee, H. Zhu, K.D. Philipson, J. Lytton, Alternative promoters and cardiac muscle cell-specific expression of the Na+/Ca2+ exchanger gene. Am. J. Physiol. 274, H217–H232 (1998)
D.A. Nicoll, S. Longoni, K.D. Philipson, Molecular cloning and functional expression of the cardiac sarcolemmal Na+-Ca2+ exchanger. Science 250, 562–565 (1990)
D.A. Nicoll, B.D. Quednau, Z. Qui, Y.R. Xia, A.J. Lusis, K.D. Philipson, Cloning of a third mammalian Na+-Ca2+ exchanger, NCX3. J. Biol. Chem. 271, 24914–24921 (1996)
M. Papa, A. Canitano, F. Boscia, P. Castaldo, S. Sellitti, H. Porzig, M. Taglialatela, L. Annunziato, Differential expression of the Na+-Ca2+ exchanger transcripts and proteins in rat brain regions. J. Comp. Neurol. 461, 31–48 (2003)
N.D. Perkins, T.D. Gilmore, Good cop, bad cop: the different faces of NF-kappaB. Cell Death Differ. 13, 759–772 (2006)
G. Pignataro, R. Gala, O. Cuomo, A. Tortiglione, L. Giaccio, P. Castaldo, R. Sirabella, C. Matrone, A. Canitano, S. Amoroso, G. Di Renzo, L. Annunziato, Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia. Stroke 35, 2566–2570 (2004)
G. Pignataro, A. Scorziello, G. Di Renzo, L. Annunziato, Post-ischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy. FEBS J. 276, 46–57 (2009)
B.D. Quednau, D.A. Nicoll, K.D. Philipson, Tissue specificity and alternative splicing of the Na+/Ca2+ exchanger isoforms NCX1, NCX2, and NCX3 in rat. Am. J. Physiol. 272, C1250–C1261 (1997)
M. Sakaue, H. Nakamura, I. Kaneko, Y. Kawasaki, N. Arakawa, H. Hashimoto, Y. Koyama, A. Baba, T. Matsuda, Na+-Ca2+ exchanger isoforms in rat neuronal preparations: different changes in their expression during postnatal development. Brain Res. 881, 212–216 (2000)
T. Scheller, A. Kraev, S. Skinner, E. Carafoli, Cloning of the multipartite promoter of the sodium-calcium exchanger gene NCX1 and characterization of its activity in vascular smooth muscle cells. J. Biol. Chem. 273, 7643–7649 (1998)
A. Secondo, R.I. Staiano, A. Scorziello, R. Sirabella, F. Boscia, A. Adornetto, V. Valsecchi, P. Molinaro, L.M. Canzoniero, G. Di Renzo, L. Annunziato, BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: possible relationship with mitochondrial membrane potential. Cell Calcium 42, 521–535 (2007)
G.L. Semenza, Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis. Blood 114, 2015–2019 (2009)
G.L. Semenza, M.K. Nejfelt, S.M. Chi, S.E. Antonarakis, Hypoxia-inducible nuclear factors bind to an enhancer element located 3′ to the human erythropoietin gene. Proc. Natl. Acad. Sci. U. S. A. 88, 5680–5684 (1991)
G.L. Semenza, B.H. Jiang, S.W. Leung, R. Passantino, J.P. Concordet, P. Maire, A. Giallongo, Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J. Biol. Chem. 271, 32529–32537 (1996)
R. Sirabella, A. Secondo, A. Pannaccione, A. Scorziello, V. Valsecchi, A. Adornetto, L. Bilo, G. Di Renzo, L. Annunziato, Anoxia-induced NF-kappaB-dependent upregulation of NCX1 contributes to Ca2+ refilling into endoplasmic reticulum in cortical neurons. Stroke 40, 922–929 (2009)
L. Smith, J.B. Smith, Regulation of sodium-calcium exchanger by glucocorticoids and growth factors in vascular smooth muscle. J. Biol. Chem. 269, 27527–27531 (1994)
S. Taie, J. Ono, Y. Iwanaga, S. Tomita, T. Asaga, K. Chujo, M. Ueki, Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning. J. Clin. Neurosci. 16, 1056–1060 (2009)
K. Tanimoto, Y. Makino, T. Pereira, L. Poellinger, Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. EMBO J. 19, 4298–4309 (2000)
V. Valsecchi, G. Pignataro, A. Del Prete, R. Sirabella, C. Matrone, F. Boscia, A. Scorziello, M.J. Sisalli, E. Esposito, N. Zambrano, G. Di Renzo, L. Annunziato, NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain preconditioning. Stroke 42, 754–763 (2011)
G.L. Wang, G.L. Semenza, Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J. Biol. Chem. 268, 21513–21518 (1993)
L. Yu, R.A. Colvin, Regional differences in expression of transcripts for Na+/Ca2+ exchanger isoforms in rat brain. Brain Res. Mol. Brain Res. 50, 285–292 (1997)
Acknowledgments
This work was supported by COFIN2008, Ricerca-Sanitaria RF-FSL352059 Ricerca finalizzata 2006, Ricerca-Oncologica 2006, Progetto-Strategico 2007, Progetto Ordinario 2007, Ricerca finalizzata 2009, Ricerca-Sanitaria Progetto Ordinario by Ministero della Salute 2008, and MIUR, Progetto Operativo Nazionale (PON) 01602 all to LA.
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Valsecchi, V. et al. (2013). Transcriptional Regulation of ncx1 Gene in the Brain. In: Annunziato, L. (eds) Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications. Advances in Experimental Medicine and Biology, vol 961. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4756-6_12
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