Abstract
The role of inflammation in neurological disorders such as Alzheimer’s disease and Parkinson’s disease is gradually recognized and leads to an urgent challenge. Smad ubiquitination regulatory factor 1 (Smurf1), one member of the HECT family, is up-regulated by proinflammatory cytokines and associated with apoptosis in acute spinal cord injury. However, the function of Smurf1 through promoting neuronal necroptosis is still limited in the central nervous system (CNS). Hence, we developed a neuroinflammatory model in adult rats following lipopolysaccharide (LPS) lateral ventral injection to elaborate whether Smurf1 is involved in necroptosis in CNS injury. The up-regulation of Smurf1 detected in the rat brain cortex was similar to the necroptotic marker RIP1 expression in a time-dependent manner after LPS-induced neuroinflammation. Meanwhile, Smurf1 knockdown with siRNA inhibited neuronal necroptosis following LPS-stimulated rat pheochromocytomal PC12 cells. Thus, it was indicated that LPS-induced necroptosis could be promoted by Smurf1. In short, these studies suggest that Smurf1 might promote neuronal necroptosis after LPS-induced neuroinflammation, which might act as a novel and potential molecular target for the treatment of neuroinflammation associated diseases.
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Cabal-Hierro L, Lazo PS (2012) Signal transduction by tumor necrosis factor receptors. Cell Signal 24(6):1297–1305. doi:10.1016/j.cellsig.2012.02.006
Chen X, Wang H, Yu W, Chen F, Wang G, Shi J, Zhou C (2016) IDH1 associated with neuronal apoptosis in adult rats brain following intracerebral hemorrhage. Cell Mol Neurobiol. doi:10.1007/s10571-016-0421-9
Chiurchiu V, Leuti A, Cencioni MT, Albanese M, De Bardi M, Bisogno T, Centonze D, Battistini L, Maccarrone M (2016) Modulation of monocytes by bioactive lipid anandamide in multiple sclerosis involves distinct Toll-like receptors. Pharmacological research 113(Pt A):313–319. doi:10.1016/j.phrs.2016.09.003
Cui Y, He S, Xing C, Lu K, Wang J, Xing G, Meng A, Jia S, He F, Zhang L (2011) SCFFBXL(1)(5) regulates BMP signalling by directing the degradation of HECT-type ubiquitin ligase Smurf1. EMBO J 30(13):2675–2689. doi:10.1038/emboj.2011.155
De Santi L, Polimeni G, Cuzzocrea S, Esposito E, Sessa E, Annunziata P, Bramanti P (2011) Neuroinflammation and neuroprotection: an update on (future) neurotrophin-related strategies in multiple sclerosis treatment. Curr Med Chem 18(12):1775–1784
Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4(5):313–321. doi:10.1038/nchembio.83
Dhib-Jalbut S, Kalvakolanu DV (2015) Microglia and necroptosis: the culprits of neuronal cell death in multiple sclerosis. Cytokine 76(2):583–584. doi:10.1016/j.cyto.2015.06.004
Fakharnia F, Khodagholi F, Dargahi L, Ahmadiani A (2016) Prevention of cyclophilin D-mediated mPTP opening using cyclosporine-A alleviates the elevation of necroptosis, autophagy and apoptosis-related markers following global cerebral ischemia-reperfusion. J Mol Neurosci. doi:10.1007/s12031-016-0843-3
Fan H, Tang HB, Kang J, Shan L, Song H, Zhu K, Wang J, Ju G, Wang YZ (2015) Involvement of endoplasmic reticulum stress in the necroptosis of microglia/macrophages after spinal cord injury. Neuroscience 311:362–373. doi:10.1016/j.neuroscience.2015.10.049
Fan H, Zhang K, Shan L, Kuang F, Chen K, Zhu K, Ma H, Ju G, Wang YZ (2016) Reactive astrocytes undergo M1 microglia/macrophages-induced necroptosis in spinal cord injury. Mol Neurodegener 11:14. doi:10.1186/s13024-016-0081-8
He M, Liu Y, Shen J, Duan C, Lu X (2016) Upregulation of PLZF is associated with neuronal injury in lipopolysaccharide-induced neuroinflammation. Neurochem Res. doi:10.1007/s11064-016-2027-5
Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8(4):382–397. doi:10.1016/S1474-4422(09)70062-6
Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K (2003) Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J 22(24):6458–6470. doi:10.1093/emboj/cdg632
Lee YS, Park JS, Kim JH, Jung SM, Lee JY, Kim SJ, Park SH (2011) Smad6-specific recruitment of Smurf E3 ligases mediates TGF-beta1-induced degradation of MyD88 in TLR4 signalling. Nat Commun 2:460. doi:10.1038/ncomms1469
Lee MG, Jeong SI, Ko KP, Park SK, Ryu BK, Kim IY, Kim JK, Chi SG (2016) RASSF1A directly antagonizes RhoA activity through the assembly of a Smurf1-mediated destruction complex to suppress tumorigenesis. Can Res 76(7):1847–1859. doi:10.1158/0008-5472.CAN-15-1752
Li D, Zhang J, Huang W, Jin H, Shen A, Yang L, Liu J, Fan J, Zhou Q, Wen H, Hu Y, Cui Z (2013) Up-regulation of Smurf1 after spinal cord injury in adult rats. J Mol Histol 44(4):381–390. doi:10.1007/s10735-013-9499-2
Li M, Wang W, Mai H, Zhang X, Wang J, Gao Y, Wang Y, Deng G, Gao L, Zhou S, Chen Q, Wang X (2016) Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice. Sci Rep 6:35055. doi:10.1038/srep35055
Liu T, Zhao DX, Cui H, Chen L, Bao YH, Wang Y, Jiang JY (2016) Therapeutic hypothermia attenuates tissue damage and cytokine expression after traumatic brain injury by inhibiting necroptosis in the rat. Sci Rep 6:24547. doi:10.1038/srep24547
Morales I, Guzman-Martinez L, Cerda-Troncoso C, Farias GA, Maccioni RB (2014) Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci 8:112. doi:10.3389/fncel.2014.00112
Nagley P, Higgins GC, Atkin JD, Beart PM (2010) Multifaceted deaths orchestrated by mitochondria in neurones. Biochem Biophys Acta 1802(1):167–185. doi:10.1016/j.bbadis.2009.09.004
Nikseresht S, Khodagholi F, Nategh M, Dargahi L (2015) RIP1 inhibition rescues from LPS-induced RIP3-mediated programmed cell death, distributed energy metabolism and spatial memory impairment. J Mol Neurosci 57(2):219–230. doi:10.1007/s12031-015-0609-3
Pannu R, Singh I (2006) Pharmacological strategies for the regulation of inducible nitric oxide synthase: neurodegenerative versus neuroprotective mechanisms. Neurochem Int 49(2):170–182. doi:10.1016/j.neuint.2006.04.010
Parajuli B, Horiuchi H, Mizuno T, Takeuchi H, Suzumura A (2015) CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia. Glia 63(12):2274–2284. doi:10.1002/glia.22892
Politi K, Przedborski S (2016) Axonal degeneration: RIPK1 multitasking in ALS. Curr Biol 26(20):R932–R934. doi:10.1016/j.cub.2016.08.052
Qian G, Ren Y, Zuo Y, Yuan Y, Zhao P, Wang X, Cheng Q, Liu J, Zhang L, Guo T, Liu C, Zheng H (2016) Smurf1 represses TNF-alpha production through ubiquitination and destabilization of USP5. Biochem Biophys Res Commun 474(3):491–496. doi:10.1016/j.bbrc.2016.04.135
Rothman AM, Arnold ND, Pickworth JA, Iremonger J, Ciuclan L, Allen RM, Guth-Gundel S, Southwood M, Morrell NW, Thomas M, Francis SE, Rowlands DJ, Lawrie A (2016) MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension. J Clin Investig 126(7):2495–2508. doi:10.1172/JCI83361
Sasso V, Bisicchia E, Latini L, Ghiglieri V, Cacace F, Carola V, Molinari M, Viscomi MT (2016) Repetitive transcranial magnetic stimulation reduces remote apoptotic cell death and inflammation after focal brain injury. J Neuroinflammation 13(1):150. doi:10.1186/s12974-016-0616-5
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11(10):700–714. doi:10.1038/nrm2970
Wen S, Ling Y, Yang W, Shen J, Li C, Deng W, Liu W, Liu K (2016) Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury. J Cell Mol Med. doi:10.1111/jcmm.12987
Wong SY, Tan MG, Banks WA, Wong WS, Wong PT, Lai MK (2016) Andrographolide attenuates LPS-stimulated up-regulation of C-C and C-X-C motif chemokines in rodent cortex and primary astrocytes. J Neuroinflammation 13:34. doi:10.1186/s12974-016-0498-6
Wu C, Chen J, Liu Y, Zhang J, Ding W, Wang S, Bao G, Xu G, Sun Y, Wang L, Chen L, Gu H, Cui B, Cui Z (2016) Upregulation of PSMB4 is associated with the necroptosis after spinal cord injury. Neurochem Res. doi:10.1007/s11064-016-2033-7
Xie Y, Guo H, Wang L, Xu L, Zhang X, Yu L, Liu Q, Li Y, Zhao N, Zhao N, Ye R, Liu X (2017) Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage. Brain Behav Immun 60:346–360. doi:10.1016/j.bbi.2016.11.004
Xu Y, Wang J, Song X, Qu L, Wei R, He F, Wang K, Luo B (2016) RIP3 induces ischemic neuronal DNA degradation and programmed necrosis in rat via AIF. Sci Rep 6:29362. doi:10.1038/srep29362
Zhang J, Yang Y, He W, Sun L (2016a) Necrosome core machinery: MLKL. Cell Mol Life Sci 73(11–12):2153–2163. doi:10.1007/s00018-016-2190-5
Zhang T, Zhang Y, Cui M, Jin L, Wang Y, Lv F, Liu Y, Zheng W, Shang H, Zhang J, Zhang M, Wu H, Guo J, Zhang X, Hu X, Cao CM, Xiao RP (2016b) CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med 22(2):175–182. doi:10.1038/nm.4017
Zhang Y, Wang C, Cao Y, Gu Y, Zhang L (2016c) Selective compounds enhance osteoblastic activity by targeting HECT domain of ubiquitin ligase Smurf1. Oncotarget. doi:10.18632/oncotarget.10648
Zhou Y, Wu Z, Cao X, Ding L, Wen Z, Bian JS (2016) HNO suppresses LPS-induced inflammation in BV-2 microglial cells via inhibition of NF-kappaB and p38 MAPK pathways. Pharmacol Res 111:885–895. doi:10.1016/j.phrs.2016.08.007
Zhu Y, Cui H, Xia Y, Gan H (2016) RIPK3-mediated necroptosis and apoptosis contributes to renal tubular cell progressive loss and chronic kidney disease progression in rats. PLoS ONE 11(6):e0156729. doi:10.1371/journal.pone.0156729
Acknowledgements
This work was partly supported by the National Natural Science Foundation of China (Nos. 81371335, 81401013, 81401365), Nantong Science and Technology Project (MS12015056), and a Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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Shao, L., Liu, X., Zhu, S. et al. The Role of Smurf1 in Neuronal Necroptosis after Lipopolysaccharide-Induced Neuroinflammation. Cell Mol Neurobiol 38, 809–816 (2018). https://doi.org/10.1007/s10571-017-0553-6
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DOI: https://doi.org/10.1007/s10571-017-0553-6