题名

Roles of NAD in Protection of Axon against Degeneration via SIRT1 Pathways

DOI

10.4077/CJP.2016.BAD331

作者

Jing Zhang;Wei-Hua Guo;Xiao-Xia Qi;Gui-Bao Li;Yan-Lai Hu;Qi Wu;Zhao-Xi Ding;Hong-Yu Li;Jing Hao;Jin-Hao Sun

关键词

axonal degeneration ; DRG ; NAD ; protection ; SIRT ; vincristine

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

59卷2期(2016 / 04 / 30)

页次

78 - 86

内容语文

英文

英文摘要

Axonal degeneration is a common pathological change of neurogenical disease which often arises before the neuron death. But it had not found any effective method to protect axon from degeneration. In this study we intended to confirm the protective effect of nicotinamide adenine dinucleotide (NAD), investigate the optimal administration dosage and time of NAD, and identify the relationship between silence signal regulating factor 1 (SIRT1) and axonal degeneration. An axonal degeneration model was established using dorsal root ganglion (DRG) neurons injured by vincristine to observe the protective effects of NAD to the injured axons. In addition, the potential contribution of the SIRT1 in axonal degeneration was also investigated. Through the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunochemistry staining, axons counting and length measuring, transmission electron microscope (TEM) observation, we demonstrated that NAD played an important role in preventing axonal degeneration. Further study revealed that the expression of SIRT1 and phosphorylated Akt1 (p-Akt1) was up-regulated when NAD was added into the culturing medium. Taking together, our results demonstrated that NAD might delay the axonal degeneration through SIRT1/Akt1 pathways.

主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Araki, T.,Sasaki, Y.,Milbrandt, J.(2004).Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration.Science,305,1010-1013.
  2. Barrientos, S.A.,Martinez, N.W.,Yoo, S.,Jara, J.S.,Zamorano, S.,Hetz, C.,Twiss, J.L.,Alvarez, J.,Court, F.A.(2011).Axonal degeneration is mediated by the mitochondrial permeability transition pore.J. Neurosci.,31,966-978.
  3. Baur, J.A.,Pearson, K.J.,Price, N.L.,Jamieson, H.A.,Lerin, C.,Kalra, A.,Prabhu, V.V.,Allard, J.S.,Lopez-Lluch, G.,Lewis, K.,Pistell, P.J.,Poosala, S.,Becker, K.G.,Boss, O.,Gwinn, D.,Wang, M.,Ramaswamy, S.,Fishbein, K.W.,Spencer, R.G.,Lakatta, E.G.,Le Couteur, D.,Shaw, R.J.,Navas, P.,Puigserver, P.,Ingram, D.K.,de Cabo, R.,Sinclair, D.A.(2006).Resveratrol improves health and survival of mice on a high-calorie diet.Nature,444,337-342.
  4. Belenky, P.,Bogan, K.L.,Brenner, C.(2007).NAD+ metabolism in health and disease.Trends Biochem. Sci.,32,12-19.
  5. Calliari, A.,Bobba, N.,Escande, C.,Chini, E.N.(2014).Resveratrol delays Wallerian degeneration in a NAD+ and DBC1 dependent manner.Exp. Neurol.,251,91-100.
  6. Chung, S.,Yao, H.,Caito, S.,Hwang, J.W.,Arunachalam, G.,Rahman, I.(2010).Regulation of SIRT1 in cellular functions: role of polyphenols.Arch Biochem. Biophys.,501,79-90.
  7. Coleman, M.P.,Perry, V.H.(2002).Axon pathology in neurological disease: a neglected therapeutic target.Trends Neurosci.,25,532-537.
  8. Di Stefano, M.,Conforti, L.(2013).Diversification of NAD biological role: the importance of location.FEBS J.,280,4711-4728.
  9. Figarska, S.M.,Vonk, J.M.,Boezen, H.M.(2013).SIRT1 polymorphism, long-term survival and glucose tolerance in the general population.PLoS One,8,e58636.
  10. Griffin, J.W.,George, E.B.,Chaudhry, V.(1996).Wallerian degeneration in peripheral nerve disease.Baillieres Clin. Neurol.,5,65-75.
  11. Hisahara, S.,Chiba, S.,Matsumoto, H.,Horio, Y.(2005).Transcriptional regulation of neuronal genes and its effect on neural functions: NAD-dependent histone deacetylase SIRT1 (Sir2alpha).J. Pharmacol. Sci.,98,200-204.
  12. Hong, Y.,Nie, H.,Wu, D.,Wei, X.,Ding, X.,Ying, W.(2014).NAD+ treatment prevents rotenone-induced apoptosis and necrosis of differentiated PC12 cells.Neurosci. Lett.,560,46-50.
  13. Jackson, J.G.,Usachev, Y.M.,Thayer, S.A.(2007).Bradykinin-induced nuclear factor of activated T-cells-dependent transcription in rat dorsal root ganglion neurons.Mol. Pharmacol.,72,303-310.
  14. Kauppinen, T.M.,Gan, L.,Swanson, R.A.(2013).Poly (ADP-ribose) polymerase-1-induced NAD+ depletion promotes nuclear factor-κB transcriptional activity by preventing p65 de-acetylation.Biochim. Biophys. Acta,1833,1985-1991.
  15. Lagouge, M.,Argmann, C.,Gerhart-Hines, Z.,Meziane, H.,Lerin, C.,Daussin, F.,Messadeq, N.,Milne, J.,Lambert, P.,Elliott, P.,Geny, B.,Laakso, M.,Puigserver, P.,Auwerx, J.(2006).Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.Cell,127,1109-1122.
  16. Liu, N.,Varma, S.,Shooter, E.M.,Tolwani, R.J.(2005).Enhancement of Schwann cell myelin formation by K252a in the Trembler-J mouse dorsal root ganglion explantculture.J. Neurosci. Res.,79,310-317.
  17. Lunn, E.R.,Perry, V.H.,Brown, M.C.,Rosen, H.,Gordon, S.(1989).Absence of Wallerian degeneration does not hinder regeneration in peripheral nerve.Eur. J. Neurosci.,1,27-33.
  18. Luo, L.,O'Leary, D.D.(2005).Axon retraction and degeneration in development and disease.Annu. Rev. Neurosci.,28,127-156.
  19. Mack, T.G.,Reiner, M.,Beirowski, B.,Mi, W.,Emanuelli, M.,Wagner, D.,Thomson, D.,Gillingwater, T.,Court, F.,Conforti, L.,Fernando, F.S.,Tarlton, A.,Andressen, C.,Addicks, K.,Magni, G.,Ribchester, R.R.,Perry, V.H.,Coleman, M.P.(2001).Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/ Nmnat chimeric gene.Nat. Neurosci.,4,1199-1206.
  20. Markus, A.,Zhong, J.,Snider, W.D.(2002).Raf and akt mediate distinct aspects of sensory axon growth.Neuron,35,65-76.
  21. Massudi, H.,Grant, R.,Guillemin, G.J.,Braidy, N.(2012).NAD+ metabolism and oxidative stress: the golden nucleotide on a crown of thorns.Redox Rep.,17,28-46.
  22. Min, S.W.,Sohn, P.D.,Cho, S.H.,Swanson, R.A.,Gan, L.(2013).Sirtuins in neurodegenerative diseases: an update on potential mechanisms.Front Aging Neurosci.,5,53-62.
  23. Mouchiroud, L.,Houtkooper, R.H.,Auwerx, J.(2013).NAD+ metabolism: a therapeutic target for age-related metabolic disease.Crit. Rev. Biochem. Mol. Biol.,48,397-408.
  24. Namikawa, K.,Honma, M.,Abe, K.,Takeda, M.,Mansur, K.,Obata, T.,Miwa, A.,Okado, H.,Kiyama, H.(2000).Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration.J. Neurosci.,20,2875-2886.
  25. Pittelli, M.,Felici, R.,Pitozzi, V.,Giovannelli, L.,Bigagli, E.,Cialdai, F.,Romano, G.,Moroni, F.,Chiarugi, A.(2011).Pharmacological effects of exogenous NAD on mitochondrial bioenergetics, DNA repair, and apoptosis.Mol. Pharmacol.,80,1136-1146.
  26. Raff, M.C.,Whitmore, A.V.,Finn, J.T.(2002).Axonal self-destruction and neurodegeneration.Science,296,868-871.
  27. Sasaki, Y.,Araki, T.,Milbrandt, J.(2006).Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.J. Neurosci.,26,8484-8491.
  28. Wang, D.,Hu, Z.,Hao, J.,He, B.,Gan, Q.,Zhong, X.,Zhang, X.,Shen, J.,Fang, J.,Jiang, W.(2013).SIRT1 inhibits apoptosis of degenerative human disc nucleus pulposus cells through activation of Akt pathway.Age,35,1741-1753.
  29. Wang, J.,He, Z.(2009).NAD and axon degeneration: from the Wlds gene to neurochemistry.Cell Adh. Migr.,3,77-87.
  30. Wang, J.,Zhai, Q.,Chen, Y.,Lin, E.,Gu, W.,McBurney, M.W.,He, Z.(2005).A local mechanism mediates NAD-dependent protection of axon degeneration.J. Cell Biol.,170,349-355.
  31. Wang, L.,Ding, D.,Salvi, R.,Roth, J.A.(2014).Nicotinamide adenine dinucleotide prevents neuroaxonal degeneration induced by manganese in cochlear organotypic cultures.Neurotoxicology,40,65-74.
  32. Yang, T.,Sauve, A.A.(2006).NAD metabolism and sirtuins: metabolic regulation of protein deacetylation in stress and toxicity.AAPS J.,8,E632-E643.
  33. Ying, W.(2013).Roles of NAD+, PARP-1, and Sirtuins in cell death, ischemic brain injury, and synchrotron radiation X-ray-induced tissue injury.Scientifica,2013,691251.
  34. Zhai, R.G.,Cao, Y.,Hiesinger, P.R.,Zhou, Y.,Mehta, S.Q.,Schulze, K.L.,Verstreken, P.,Bellen, H.J.(2006).Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity.PLoS Biol.,4,e416.
  35. Zhang, J.,Feng, X.,Wu, J.,Xu, H.,Li, G.,Zhu, D.,Yue, Q.,Liu, H.,Zhang, Y.,Sun, D.,Wang, H.,Sun, J.(2014).Neuroprotective effects of resveratrol on damages of mouse cortical neurons induced by β-amyloid through activation of SIRT1/Akt1 pathway.Biofactors,40,258-267.
  36. Zheng, C.,Han, J.,Xia, W.,Shi, S.,Liu, J.,Ying, W.(2012).NAD+ administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia.Neurosci. Lett.,512,67-71.