DOI QR코드

DOI QR Code

Nicotinamide Mononucleotide Adenylyl Transferase 2 Inhibition Aggravates Neurological Damage after Traumatic Brain Injury in a Rat Model

  • Xiaoyu Gu (Department of Intensive Care Unit, The Affiliated Zhangjiagang Hospital of Soochow University) ;
  • Haibo Ni (Department of Neurosurgery, The Affiliated Zhangjiagang Hospital of Soochow University) ;
  • XuGang Kan (Department of Neurobiology, The Affiliated Xuzhou Medical University) ;
  • Chen Chen (Department of Intensive Care Unit, The Affiliated Zhangjiagang Hospital of Soochow University) ;
  • Zhiping Zhou (Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University) ;
  • Zheng Ding (Department of Intensive Care Unit, The Affiliated Zhangjiagang Hospital of Soochow University) ;
  • Di Li (Department of Intensive Care Unit, The Affiliated Zhangjiagang Hospital of Soochow University) ;
  • Bofei Liu (Department of Intensive Care Unit, The Affiliated Zhangjiagang Hospital of Soochow University)
  • 투고 : 2022.05.18
  • 심사 : 2022.10.23
  • 발행 : 2023.07.01

초록

Objective : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

키워드

참고문헌

  1. Autret A, Martin SJ : Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis. Mol Cell 36 : 355-363, 2009  https://doi.org/10.1016/j.molcel.2009.10.011
  2. Babetto E, Beirowski B, Russler EV, Milbrandt J, DiAntonio A : The Phr1 ubiquitin ligase promotes injury-induced axon self-destruction. Cell Rep 3 : 1422-1429, 2013  https://doi.org/10.1016/j.celrep.2013.04.013
  3. Berger F, Lau C, Dahlmann M, Ziegler M : Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms. J Biol Chem 280 : 36334-36341, 2005  https://doi.org/10.1074/jbc.M508660200
  4. Cai Y, Yu SS, Chen SR, Pi RB, Gao S, Li H, et al. : Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6. FEBS Lett 586 : 866-874, 2012  https://doi.org/10.1016/j.febslet.2012.02.014
  5. Carteri RB, Kopczynski A, Rodolphi MS, Strogulski NR, Sartor M, Feldmann M, et al. : Testosterone administration after traumatic brain injury reduces mitochondrial dysfunction and neurodegeneration. J Neurotrauma 36 : 2246-2259, 2019  https://doi.org/10.1089/neu.2018.6266
  6. Ding C, Hammarlund M : Mechanisms of injury-induced axon degeneration. Curr Opin Neurobiol 57 : 171-178, 2019  https://doi.org/10.1016/j.conb.2019.03.006
  7. Ekert PG, Read SH, Silke J, Marsden VS, Kaufmann H, Hawkins CJ, et al. : Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die. J Cell Biol 165 : 835-842, 2004  https://doi.org/10.1083/jcb.200312031
  8. Gerdts J, Brace EJ, Sasaki Y, DiAntonio A, Milbrandt J : SARM1 activation triggers axon degeneration locally via NAD+ destruction. Science 348 : 453-457,
  9. Gerdts J, Summers DW, Milbrandt J, DiAntonio A : Axon self-destruction: new links among SARM1, MAPKs, and NAD+ metabolism. Neuron 89 : 449-460, 2016  https://doi.org/10.1016/j.neuron.2015.12.023
  10. Henninger N, Bouley J, Sikoglu EM, An J, Moore CM, King JA, et al. : Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1. Brain 139 : 1094-1105, 2016  https://doi.org/10.1093/brain/aww001
  11. Huang J, Tang D, Cao Y, Wang Y, Long J, Wei L, et al. : Inhibition of PDE10A-rescued TBI-induced neuroinflammation and apoptosis through the cAMP/PKA/NLRP3 pathway. Evid Based Complement Alternat Med 2022 : 3311250, 2022 
  12. Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC : The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation 22 : 341-353, 2007  https://doi.org/10.3233/NRE-2007-22502
  13. Jayaram HN, Kusumanchi P, Yalowitz JA : NMNAT expression and its relation to NAD metabolism. Curr Med Chem 18 : 1962-1972, 2011  https://doi.org/10.2174/092986711795590138
  14. Jennings JS, Gerber AM, Vallano ML : Pharmacological strategies for neuroprotection in traumatic brain injury. Mini Rev Med Chem 8 : 689-701, 2008  https://doi.org/10.2174/138955708784567377
  15. Lau C, Niere M, Ziegler M : The NMN/NaMN adenylyltransferase (NMNAT) protein family. Front Biosci (Landmark Ed) 14 : 410-431, 2009  https://doi.org/10.2741/3252
  16. Li D, Ni H, Rui Q, Gao R, Chen G : Deletion of Mst1 attenuates neuronal loss and improves neurological impairment in a rat model of traumatic brain injury. Brain Res 1688 : 15-21, 2018  https://doi.org/10.1016/j.brainres.2017.10.018
  17. Loreto A, Di Stefano M, Gering M, Conforti L : Wallerian degeneration is executed by an NMN-SARM1-dependent late Ca(2+) influx but only modestly influenced by mitochondria. Cell Rep 13 : 2539-2552,
  18. Menon DK, Schwab K, Wright DW, Maas AI; Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health : Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil 91 : 1637-1640, 2010  https://doi.org/10.1016/j.apmr.2010.05.017
  19. Mete M, Aydemir I, Unsal UU, Collu F, Vatandas G, Gurcu B, et al. : Neuroprotective effects of oleocanthal, a compound in virgin olive oil, in a rat model of traumatic brain injury. Turk Neurosurg 28 : 858-865, 2018 
  20. Mouchiroud L, Houtkooper RH, Auwerx J : NAD+ metabolism: a therapeutic target for age-related metabolic disease. Crit Rev Biochem Mol Biol 48 : 397-408, 2013  https://doi.org/10.3109/10409238.2013.789479
  21. Orsomando G, Cialabrini L, Amici A, Mazzola F, Ruggieri S, Conforti L, et al. : Simultaneous single-sample determination of NMNAT isozyme activities in mouse tissues. PLoS One 7 : e53271, 2012 
  22. Sabirzhanov B, Faden AI, Aubrecht T, Henry R, Glaser E, Stoica BA : MicroRNA-711-induced downregulation of angiopoietin-1 mediates neuronal cell death. J Neurotrauma 35 : 2462-2481, 2018  https://doi.org/10.1089/neu.2017.5572
  23. Sabirzhanov B, Zhao Z, Stoica BA, Loane DJ, Wu J, Borroto C, et al. : Downregulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of proapoptotic Bcl-2 proteins. J Neurosci 34 : 10055-10071, 2014  https://doi.org/10.1523/JNEUROSCI.1260-14.2014
  24. Shen H, Chen Z, Wang Y, Gao A, Li H, Cui Y, et al. : Role of neurexin-1ss and neuroligin-1 in cognitive dysfunction after subarachnoid hemorrhage in rats. Stroke 46 : 2607-2615,
  25. Summers DW, Gibson DA, DiAntonio A, Milbrandt J : SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation. Proc Natl Acad Sci U S A 113 : E6271-E6280, 2016  https://doi.org/10.1073/pnas.1601506113
  26. Wang Y, Gao A, Xu X, Dang B, You W, Li H, et al. : The neuroprotection of lysosomotropic agents in experimental subarachnoid hemorrhage probably involving the apoptosis pathway triggering by cathepsins via chelating intralysosomal iron. Mol Neurobiol 52 : 64-77, 2015 https://doi.org/10.1007/s12035-014-8846-y
  27. 27 Wang Y, Liu Y, Lopez D, Lee M, Dayal S, Hurtado A, et al. : Protection against TBI-induced neuronal death with post-treatment with a selective calpain-2 inhibitor in mice. J Neurotrauma 35 : 105-117, 2018  https://doi.org/10.1089/neu.2017.5024
  28. Yamagishi Y, Tessier-Lavigne M : An atypical SCF-like ubiquitin ligase complex promotes wallerian degeneration through regulation of axonal Nmnat2. Cell Rep 17 : 774-782, 2016  https://doi.org/10.1016/j.celrep.2016.09.043
  29. Yang J, Wu Z, Renier N, Simon DJ, Uryu K, Park DS, et al. : Pathological axonal death through a MAPK cascade that triggers a local energy deficit. Cell 160 : 161-176, 2015  https://doi.org/10.1016/j.cell.2014.11.053
  30. Zhao Z, Zhou Y, Tian Y, Li M, Dong JF, Zhang J : Cellular microparticles and pathophysiology of traumatic brain injury. Protein Cell 8 : 801-810, 2017 https://doi.org/10.1007/s13238-017-0414-6