Portal de Periódicos da CAPES

Do RCAN1 proteins link chronic stress with neurodegeneration?

2011; Wiley; Volume: 25; Issue: 10 Linguagem: Inglês

10.1096/fj.11-185728

1530-6860

Gennady Ermak, Melanie Pritchard, Sladjana Dronjak, Brenda Niu, Kelvin J.A. Davies,

Neuropeptides and Animal Physiology

The FASEB JournalVolume 25, Issue 10 p. 3306-3311 HypothesisFree to Read Do RCAN1 proteins link chronic stress with neurodegeneration? Gennady Ermak, Gennady Ermak Ethel Percy Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, California, USA Division of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, USASearch for more papers by this authorMelanie A. Pritchard, Melanie A. Pritchard Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, AustraliaSearch for more papers by this authorSladjana Dronjak, Sladjana Dronjak Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences Vinca, Belgrade, SerbiaSearch for more papers by this authorBrenda Niu, Brenda Niu Ethel Percy Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, California, USA Division of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, USASearch for more papers by this authorKelvin J. A. Davies, Corresponding Author Kelvin J. A. Davies [email protected] Ethel Percy Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, California, USA Division of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, USACorrespondence: Andrus Gerontology Center, University of Southern California, 3715 McClintock Ave., Los Angeles, CA 90089–0191, USA. E-mail: [email protected]Search for more papers by this author Gennady Ermak, Gennady Ermak Ethel Percy Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, California, USA Division of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, USASearch for more papers by this authorMelanie A. Pritchard, Melanie A. Pritchard Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, AustraliaSearch for more papers by this authorSladjana Dronjak, Sladjana Dronjak Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences Vinca, Belgrade, SerbiaSearch for more papers by this authorBrenda Niu, Brenda Niu Ethel Percy Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, California, USA Division of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, USASearch for more papers by this authorKelvin J. A. Davies, Corresponding Author Kelvin J. A. Davies [email protected] Ethel Percy Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, California, USA Division of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California, USACorrespondence: Andrus Gerontology Center, University of Southern California, 3715 McClintock Ave., Los Angeles, CA 90089–0191, USA. E-mail: [email protected]Search for more papers by this author First published: 16 June 2011 https://doi.org/10.1096/fj.11-185728Citations: 34Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT It has long been suspected that chronic stress can exacerbate, or even cause, disease. We now propose that the RCAN1 gene, which can generate several RCAN1 protein isoforms, may be at least partially responsible for this phenomenon. We review data showing that RCAN1 proteins can be induced by multiple stresses, and present new data also implicating psychosocial/emotional stress in RCAN1 induction. We further show that transgenic mice overexpressing the RCAN1-1L protein exhibit accumulation of hyperphosphorylated tau protein (AT8 antibody), an early precursor to the formation of neurofibrillary tangles and neurodegeneration of the kind seen in Alzheimer disease. We propose that, although transient induction of the RCAN1 gene might protect cells against acute stress, persistent stress may cause chronic RCAN1 overexpression, resulting in serious side effects. Chronically elevated levels of RCAN1 proteins may promote or exacerbate various diseases, including tauopathies such as Alzheimer disease. We propose that the mechanism by which stress can lead to these diseases involves the inhibition of calcineurin and the induction of GSK-3β by RCAN1 proteins. Both inhibition of calcineurin and induction of GSK-3β contribute to accumulation of phosphorylated tau, formation of neurofibrillary tangles, and eventual neurodegeneration.—Ermak, G., Pritchard, M. A., Dronjak, S., Niu, B., Davies, K. J. A. Do RCAN1 proteins link chronic stress with neurodegeneration? FASEB J. 25, 3306–3311 (2011). www.fasebj.org REFERENCES 1Crawford, D. R., Leahy, K. P., Abramova, N., Lan, L., Wang, Y., and Davies, K. J. (1997) Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress. Arch. Biochem. Biophys. 342, 6–12 2Fuentes, J. J., Pritchard, M. A., Planas, A. M., Bosch, A., Ferrer, I., and Estivill, X. (1995) A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart. Hum. Mol. Gen. 4, 1935–1944 3Davies, K. J., Ermak, G., Rothermel, B. A., Pritchard, M., Heitman, J., Ahnn, J., Henrique-Silva, F., Crawford, D., Canaider, S., Strippoli, P., Carinci, P., Min, K. T., Fox, D. S., Cunningham, K. W., Bassel-Duby, R., Olson, E. N., Zhang, Z., Williams, R. S., Gerber, H. P., Perez-Riba, M., Seo, H., Cao, X., Klee, C. B., Redondo, J. M., Maltais, L. J., Bruford, E. A., Povey, S., Molkentin, J. D., McKeon, F. D., Duh, E. J., Crabtree, G. R., Cyert, M. S., de la Luna, S., and Estivill, X. (2007) Renaming the DSCR1/Adapt78 gene family as RCAN: regulators of calcineurin. FASEB J. 21, 3023–3028 4Chang, K. T., and Min, K. T. (2005) Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function. Nat. Neurosci. 8, 1577–1585 5Cho, Y. J., Abe, M., Kim, S. Y., and Sato, Y. (2005) Raf-1 is a binding partner of DSCR1. Arch. Biochem. Biophys. 439, 121–128 6Ermak, G., Harris, C. D., and Davies, K. J. (2002) The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress. FASEB J. 16, 814–824 7Ermak, G., Harris, C. D., Battocchio, D., and Davies, K. J. (2006) RCAN1 (DSCR1 or Adapt78) stimulates expression of GSK-3beta. FEBS J. 273, 2100–2109 8Ermak, G., Morgan, T. E., and Davies, K. J. (2001) Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease. J. Biol. Chem. 276, 38787–38794 9Wang, Y., De Keulenaer, G. W., Weinberg, E. O., Muangman, S., Gualberto, A., Landschulz, K. T., Turi, T. G., Thompson, J. F., and Lee, R. T. (2002) Direct biomechanical induction of endogenous calcineurin inhibitor Down syndrome critical region-1 in cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 283, H533–H539 10Shen, M. U. L., Oshida, T., Miyauchi, J., Yamada, M., and Miyashita, T. (2004) Identification of novel direct transcriptional targets of glucocorticoid receptor. Leukemia 18, 1850–1856 11Hirakawa, Y., Nary, L. J., and Medh, R. D. (2009) Glucocorticoid evoked upregulation of RCAN1–1 in human leukemic CEM cells susceptible to apoptosis. J. Mol. Signal. 4, 6 12Goldkuhl, R., Klockars, A., Carlsson, H. E., Hau, J., and Abelson, K. S. Impact of surgical severity and analgesic treatment on plasma corticosterone in rats during surgery. Eur. Surg. Res. 44, 117–123 13Gavrilovic, L., Spasojevic, N., and Dronjak, S. (2010) Chronic individual housing-induced stress decreased expression of catecholamine biosynthetic enzyme genes and proteins in spleen of adult rats. Neuroimmunomodulation 17, 265–269 14Joels, M. (2008) Functional actions of corticosteroids in the hippocampus. Eur. J. Pharmacol. 583, 312–321 15Woon, F. L., Sood, S., and Hedges, D. W. Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: a meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatr. 34, 1181–1188 16Piazza, O., Siren, A. L., and Ehrenreich, H. (2004) Soccer, neurotrauma and amyotrophic lateral sclerosis: is there a connection? Curr. Med. Res. Opin. 20, 505–508 17Guo, Z., Cupples, L. A., Kurz, A., Auerbach, S. H., Volicer, L., Chui, H., Green, R. C., Sadovnick, A. D., Duara, R., De Carli, C., Johnson, K., Go, R. C., Growdon, J. H., Haines, J. L., Kukull, W. A., and Farrer, L. A. (2000) Head injury and the risk of AD in the MIRAGE study. Neurology 54, 1316–1323 18Chio, A., Benzi, G., Dossena, M., Mutani, R., and Mora, G. (2005) Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 128, 472–476 19Clausen, H., McCrory, P., and Anderson, V. (2005) The risk of chronic traumatic brain injury in professional boxing: change in exposure variables over the past century. Br. J. Sports Med. 39, 661–664; discussion 664 20Graves, A. B., White, E., Koepsell, T. D., Reifler, B. V., van Belle, G., Larson, E. B., and Raskind, M. (1990) The association between head trauma and Alzheimer's disease. Am. J. Epidemiol. 131, 491–501 21Wilson, R. S., Barnes, L. L., Bennett, D. A., Li, Y., Bienias, J. L., Mendes de Leon, C. F., and Evans, D. A. (2005) Proneness to psychological distress and risk of Alzheimer disease in a biracial community. Neurology 64, 380–382 22Jeong, Y. H., Park, C. H., Yoo, J., Shin, K. Y., Ahn, S. M., Kim, H. S., Lee, S. H., Emson, P. C., and Suh, Y. H. (2006) Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APPV717I-CT100 transgenic mice, an Alzheimer's disease model. FASEB J. 20, 729–731 23Korneyev, A., Binder, L., and Bernardis, J. (1995) Rapid reversible phosphorylation of rat brain tau proteins in response to cold water stress. Neurosci. Lett. 191, 19–22 24Papasozomenos, S. C. (1996) Heat shock induces rapid dephosphorylation of tau in both female and male rats followed by hyperphosphorylation only in female rats: implications for Alzheimer's disease. J. Neurochem. 66, 1140–1149 25Yanagisawa, M., Planel, E., Ishiguro, K., and Fujita, S. C. (1999) Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer's disease. FEBS Lett. 461, 329–333 26Cook, C. N., Hejna, M. J., Magnuson, D. J., and Lee, J. M. (2005) Expression of calcipressin1, an inhibitor of the phosphatase calcineurin, is altered with aging and Alzheimer's disease. J. Alzheimers Dis. 8, 63–73 27Harris, C. D., Ermak, G., and Davies, K. J. (2007) RCAN1–1L is overexpressed in neurons of Alzheimer's disease patients. FEBS J. 274, 1715–1724 28Fuentes, J. J., Genesca, L., Kingsbury, T. J., Cunningham, K. W., Perez-Riba, M., Estivill, X., and de la Luna, S. (2000) DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Hum. Mol. Genet. 9, 1681–1690 29Baek, K. H., Zaslavsky, A., Lynch, R. C., Britt, C., Okada, Y., Siarey, R. J., Lensch, M. W., Park, I. H., Yoon, S. S., Minami, T., Korenberg, J. R., Folkman, J., Daley, G. Q., Aird, W. C., Galdzicki, Z., and Ryeom, S. (2009) Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 459, 1126–1130 30Chang, K. T., Shi, Y. J., and Min, K. T. (2003) The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: implications for mental retardation. Proc. Natl. Acad. Sci. U. S. A. 100, 15794–15799 31Porta, S., Serra, S. A., Huch, M., Valverde, M. A., Llorens, F., Estivill, X., Arbones, M. L., and Marti, E. (2007) RCAN1 (DSCR1) increases neuronal susceptibility to oxidative stress: a potential pathogenic process in neurodegeneration. Hum. Mol. Genet. 16, 1039–1050 32Ladner, C. J., Czech, J., Maurice, J., Lorens, S. A., and Lee, J. M. (1996) Reduction of calcineurin enzymatic activity in Alzheimer's disease: correlation with neuropathologic changes. J. Neuropathol. Exp. Neurol. 55, 924–931 33Goto, S., Matsukado, Y., Mihara, Y., Inoue, N., and Miyamoto, E. (1986) The distribution of calcineurin in rat brain by light and electron microscopic immunohistochemistry and enzyme-immunoassay. Brain Res. 397, 161–172 34Kuno, T., Mukai, H., Ito, A., Chang, C. D., Kishima, K., Saito, N., and Tanaka, C. (1992) Distinct cellular expression of calcineurin A alpha and A beta in rat brain. J. Neurochem. 58, 1643–1651 35Garver, T. D., Kincaid, R. L., Conn, R. A., and Billingsley, M. L. (1999) Reduction of calcineurin activity in brain by antisense oligonucleotides leads to persistent phosphorylation of tau protein at Thr181 and Thr231. Mol. Pharmacol. 55, 632–641 36Kayyali, U. S., Zhang, W., Yee, A. G., Seidman, J. G., and Potter, H. (1997) Cytoskeletal changes in the brains of mice lacking calcineurin A alpha. J. Neurochem. 68, 1668–1678 37Xie, H. Q., and Johnson, G. V. (1998) Calcineurin inhibition prevents calpain-mediated proteolysis of tau in differentiated PC12 cells. J. Neurosci. Res. 53, 153–164 38Poppek, D., Keck, S., Ermak, G., Jung, T., Stolzing, A., Ullrich, O., Davies, K. J., and Grune, T. (2006) Phosphorylation inhibits turnover of the tau protein by the proteasome: influence of RCAN1 and oxidative stress. Biochem. J. 400, 511–520 39Mattsson, N., Zetterberg, H., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S. K., van der Flier, W. M., Blankenstein, M. A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M., Tsolaki, M., Mulugeta, E., Rosen, E., Aarsland, D., Visser, P. J., Schroder, J., Marcusson, J., de Leon, M., Hampel, H., Scheltens, P., Pirttila, T., Wallin, A., Jonhagen, M. E., Minthon, L., Winblad, B., and Blennow, K. (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302, 385–393 40Iqbal, K., and Grundke-Iqbal, I. (2008) Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J. Cell. Mol. Med. 12, 38–55 41Martinez, A., and Perez, D. I. (2008) GSK-3 inhibitors: a ray of hope for the treatment of Alzheimer's disease? J. Alzheimers Dis. 15, 181–191 42Keating, D. J., Dubach, D., Zanin, M. P., Yu, Y., Martin, K., Zhao, Y. F., Chen, C., Porta, S., Arbones, M. L., Mittaz, L., and Pritchard, M. A. (2008) DSCR1/RCAN1 regulates vesicle exocytosis and fusion pore kinetics: implications for Down syndrome and Alzheimer's disease. Hum. Mol. Genet. 17, 1020–1030 43Morsch, R., Simon, W., and Coleman, P. D. (1999) Neurons may live for decades with neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 58, 188–197 44Michtalik, H. J., Narayan, A. V., Bhatt, N., Lin, H. Y., Mulligan, M. T., Zhang, S. L., and Crawford, D. R. (2004) Multiple oxidative stress-response members of the Adapt78 family. Free Radic. Biol. Med. 37, 454–462 Citing Literature Volume25, Issue10October 2011Pages 3306-3311 ReferencesRelatedInformation