Abstract
Nitric oxide (NO) is involved in many neuronal functions such as neuromodulation and intracellular signaling. Recent studies have demonstrated that nitric oxide is involved in regulation of proteasomal protein degradation. However, its role in neuronal protein degradation still remains unclear. In our study, we investigated the influence of endogenous nitric oxide production in this process. We have shown that nitric oxide synthase blockade prevents decline of the UbG76V-GFP fluorescence (GFP-based proteasomal protein degradation reporter) in neuronal processes of the cultured hippocampal neurons. It suggests that nitric oxide may regulate ubiquitin-dependent proteasomal protein degradation in neurons. Also, we have confirmed that the NO synthesis blockade alone significantly impairs long-term potentiation, and demonstrated for the first time that simultaneous blockade of the NO and proteins synthesis leads to the long-term potentiation amplitude rescue to the control values. Obtained results suggest that nitric oxide is involved in the protein degradation in proteasomes in physiological conditions.
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Asano S, Fukuda Y, Beck F, Aufderheide A, Förster F, Danev R, Baumeister W (2015) A molecular census of 26. Science 347:439–442. doi:10.1126/science.1261197
Balaban PM, Roshchin MV, Korshunova TA (2011) Two-faced nitric oxide is necessary for both erasure and consolidation of memory. Zh Vyss Nerv Deiat Im I P Pavlov 61:274–280
Balaban PM, Roshchin M, Timoshenko AK, Gainutdinov KL, Bogodvid TK, Muranova LN, Zuzina AB, Korshunova TA (2014) Nitric oxide is necessary for labilization of a consolidated context memory during reconsolidation in terrestrial snails. Eur J Neurosci 40:2963–2970. doi:10.1111/ejn.12642
Bingol B, Schuman EM (2006) Activity-dependent dynamics and sequestration of proteasomes in dendritic spines. Nature 441:1144–1148. doi:10.1038/nature04769
Cai F, Frey JU, Sanna PP, Behnisch T (2010) Protein degradation by the proteasome is required for synaptic tagging and the heterosynaptic stabilization of hippocampal late-phase long-term potentiation. Neuroscience 169:1520–1526. doi:10.1016/j.neuroscience.2010.06.032
Chung KKK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, Dawson VL, Dawson TM (2004) S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function. Science 304:1328–1331. doi:10.1126/science.1093891
Colledge M, Snyder EM, Crozier RA, Soderling JA, Jin Y, Langeberg LK, Lu H, Bear MF, Scott JD (2003) Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron 40:595–607. doi:10.1016/S0896-S6273(03)00687-1
Dantuma NP, Lindsten K, Glas R, Jellne M, Masucci MG (2000) Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nat Biotechnol 18:538–543. doi:10.1038/75406
Djakovic SN, Schwarz LA, Barylko B, DeMartino GN, Patrick GN (2009) Regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase II. J Biol Chem 284:26655–26665. doi:10.1074/jbc.M109.021956
Dong C, Upadhya SC, Ding L, Smith TK, Hegde AN (2008) Proteasome inhibition enhances the induction and impairs the maintenance of late-phase long-term potentiation. Learn Mem 15:335–347. doi:10.1101/lm.984508
Ferreira JS, Schmidt J, Rio P, Aguas R, Rooyakkers A, Li KW, Smit AB, Craig AM, Carvalho AL (2015) GluN2B-containing NMDA receptors regulate AMPA receptor traffic through anchoring of the synaptic proteasome. J Neurosci 35:8462–8479. doi:10.1523/JNEUROSCI.3567-14.2015
Fonseca R (2012) Activity-dependent actin dynamics are required for the maintenance of long-term plasticity and for synaptic capture. Eur J Neurosci 35:195–206. doi:10.1111/j.1460-9568.2011.07955.x
Fonseca R, Nägerl UV, Bonhoeffer T (2006a) Neuronal activity determines the protein synthesis dependence of long-term potentiation. Nat Neurosci 9:478–480
Fonseca R, Vabulas RM, Hartl FU, Bonhoeffer T, Nagerl UV (2006b) A balance of protein synthesis and proteasome-dependent degradation determines the maintenance of LTP. Neuron 52:239–245. doi:10.1016/j.neuron.2006.08.015
Frey U, Krug M, Reymann KG, Matthies H (1988) Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res 452:57–65. doi:10.1016/0006-8993(88)90008-X
Guo L, Wang Y (2007) Glutamate stimulates glutamate receptor interacting protein 1 degradation by ubiquitin-proteasome system to regulate surface expression of GluR2. Neuroscience 145:100–109. doi:10.1016/j.neuroscience.2006.11.042
Jarome TJ, Helmstetter FJ (2014) Protein degradation and protein synthesis in long-term memory formation. Front Mol Neurosci 7:61. doi:10.3389/fnmol.2014.00061
Johnstone VPA, Raymond CR (2011) A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation. Learn Mem 18:625–633. doi:10.1101/lm.2245911
Karpova A, Mikhaylova M, Thomas U, Knopfel T, Behnisch T (2006) Involvement of protein synthesis and degradation in long- term potentiation of schaffer collateral CA1 synapses. J Neurosci 26:4949–4955. doi:10.1523/JNEUROSCI.4573-05.2006
Kwak Y-D, Ma T, Diao S, Zhang X, Chen Y, Hsu J, Lipton SA, Masliah E, Xu H, Liao F-F (2010) NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegeneration. Mol Neurodegener 5:49. doi:10.1186/1750-1326-5-49
Lee S-H, Choi J-H, Lee N, Lee H-R, Kim J-I, Yu N-K, Choi S-L, Lee S-H, Kim H, Kaang B-K (2008) Synaptic protein degradation underlies destabilization of retrieved fear memory. Science 319:1253–1256. doi:10.1126/science.1150541
Lee SH, Kwak C, Shim J, Kim JE, Choi SL, Kim HF, Jang DJ, Lee JA, Lee K, Lee CH, Lee YD, Miniaci MC, Bailey CH, Kandel ER, Kaang BK (2012) A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia. Proc Natl Acad Sci USA 109:14200–14205. doi:10.1073/pnas.1211997109
Lipton (2005) Comment on “S-Nitrosylation of Parkin regulates ubiquitination and compromises Parkins’s protective function. Science 308:1110135. doi:10.1126/science.1110135
Milton AL, Merlo E, Ratano P, Gregory BL, Dumbreck JK, Everitt BJ (2013) Double dissociation of the requirement for GluN2B- and GluN2A-containing NMDA receptors in the destabilization and restabilization of a reconsolidating memory. J Neurosci 33:1109–1115. doi:10.1523/JNEUROSCI.3273-12.2013
Musleh WY, Shahi K, Baudry M (1993) Further studies concerning the role of nitric oxide in LTP induction and maintenance. Synapse 13:370–375. doi:10.1002/syn.890130409
Nakamura T, Wang L, Wong CCL, Scott FL, Eckelman BP, Han X, Tzitzilonis C, Meng F, Gu Z, Holland EA, Clemente AT, Okamoto SI, Salvesen GS, Riek R, Yates JR, Lipton SA (2010) Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Mol Cell 39:184–195. doi:10.1016/j.molcel.2010.07.002
Naskar S, Wan H, Kemenes G (2014) pT305-CaMKII stabilizes a learning-induced increase in AMPA receptors for ongoing memory consolidation after classical conditioning. Nat Commun 5:3967. doi:10.1038/ncomms4967
Opattova A, Cente M, Novak M, Filipcik P (2015) The ubiquitin proteasome system as a potential therapeutic target for treatment of neurodegenerative diseases. Gen Physiol Biophys 34:337–352
Ozawa K, Komatsubara AT, Nishimura Y, Sawada T, Kawafune H, Tsumoto H, Tsuji Y, Zhao J, Kyotani Y, Tanaka T, Takahashi R, Yoshizumi M (2013) S-nitrosylation regulates mitochondrial quality control via activation of parkin. Sci Rep 3:2202. doi:10.1038/srep02202
Palumbo A, Fiore G, Di Cristo C, Di Cosmo A, D’Ischia M (2002) NMDA receptor stimulation induces temporary alpha-tubulin degradation signaled by nitric oxide-mediated tyrosine nitration in the nervous system of Sepia officinalis. Biochem Biophys Res Commun 293:1536–1543. doi:10.1016/S0006-S0291X(02)00392-00393
Peng ZF, Chen MJ, Yap YW, Manikandan J, Melendez AJ, Choy MS, Moore PK, Cheung NS (2008) Proteasome inhibition: an early or late event in nitric oxide-induced neuronal death? Nitric Oxide 18:136–145. doi:10.1016/j.niox.2007.11.002
Phillips KG, Hardingham NR, Fox K (2008) Postsynaptic action potentials are required for nitric-oxide-dependent long-term potentiation in CA1 neurons of adult GluR1 knock-out and wild-type mice. J Neurosci 28:14031–14041. doi:10.1523/JNEUROSCI.3984-08.2008
Shang T, Kotamraju S, Zhao H, Kalivendi SV, Hillard CJ, Kalyanaraman B (2005) Sepiapterin attenuates 1-methyl-4-phenylpyridinium-induced apoptosis in neuroblastoma cells transfected with neuronal NOS: role of tetrahydrobiopterin, nitric oxide, and proteasome activation. Free Radic Biol Med 39:1059–1074. doi:10.1016/j.freeradbiomed.2005.05.022
Tai H-C, Schuman EM (2008) Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat Rev Neurosci 9:826–838. doi:10.1038/nrn2499
Williams JH, Li YG, Nayak A, Errington ML, Murphy KPSJ, Bliss TVP (1993) The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent. Neuron 11:877–884. doi:10.1016/0896-6273(93)90117-A
Acknowledgments
This research was funded by RFBR Grant no 14-04-31663. Experiments in cultures were supported by the Russian Science Foundation Grant 14-25-00072. We would like to thank Sams D.S. and Fonar G. for English editing of the manuscript.
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The authors declare that they have no conflict of interest.
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Bal, N., Roshchin, M., Salozhin, S. et al. Nitric Oxide Upregulates Proteasomal Protein Degradation in Neurons. Cell Mol Neurobiol 37, 763–769 (2017). https://doi.org/10.1007/s10571-016-0413-9
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DOI: https://doi.org/10.1007/s10571-016-0413-9