Login Register Cart 0
General Research Article

FBXW7alpha促进创伤性脊髓的恢复

卷 20, 期 6, 2020

页: [494 - 504] 页: 11

弟呕挨: 10.2174/1566524020666191223164916

价格: $65

摘要

背景：脊髓损伤（SCI）引起白质损伤和神经元细胞死亡。研究了FBXW7α，它是细胞分裂和生长的重要介体，以探讨其在修复大鼠脊髓损伤中的作用。还研究了诸如氧化应激和炎症小体信号转导的潜在机制。 方法：通过从背面下部至中胸椎的纵向外科手术切口，然后在裸露的Th12表面放置20 g重量30分钟，建立大鼠脊髓损伤。将AAV递送的FBXW7α和-sh-FBXW7α鞘内注射到大鼠脊髓中。通过Western印迹，Elisa和RT-PCR测量氧化，神经营养因子和发烧指数。 结果：我们发现FBXW7α在损伤引起的脊髓挽救性神经元死亡中过表达。具体而言，改善了营养状况，氧化应激和发烧。各个组中BNDF和GDNF表达模式的同步表明神经营养因子的分泌影响SCI的结局。创伤后，SOD1，CAT和GSH-px被抑制，但都因FBXW7α过表达而恢复。受伤后发生炎症小体激活的细胞凋亡，在将FBXW7α导入损伤的脐带后，相关的生物标志物如GSDMD，caspase-1，caspase-11，IL-1β和IL-18被下调。此外，上调FBXW7α还可以修复线粒体功能障碍。 结论：我们的数据表明FBXW7α可能是治疗脊髓损伤的重要分子靶标。

关键词: FBXW7α，脊髓损伤，发烧，氧化应激，胱天蛋白酶信号转导，炎症小体。

« Previous
[1]
Widerström-Noga E. Neuropathic pain and spinal cord injury: phenotypes and pharmacological management. Drugs 2017; 77(9): 967-84.
[http://dx.doi.org/10.1007/s40265-017-0747-8] [PMID: 28451808]
[2]
Ahuja CS, Wilson JR, Nori S, et al. Traumatic spinal cord injury. Nat Rev Dis Primers 2017; 3: 17018.
[http://dx.doi.org/10.1038/nrdp.2017.18] [PMID: 28447605]
[3]
Granger N, Carwardine D. Acute spinal cord injury: tetraplegia and paraplegia in small animals. Vet Clin North Am Small Anim Pract 2014; 44(6): 1131-56.
[http://dx.doi.org/10.1016/j.cvsm.2014.07.013] [PMID: 25441629]
[4]
Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Warsz) 2011; 71(2): 281-99.
[PMID: 21731081]
[5]
Park J, Decker JT, Margul DJ, et al. Local immunomodulation with anti-inflammatory cytokine-encoding lentivirus enhances functional recovery after spinal cord injury. Mol Ther 2018; 26(7): 1756-70.
[http://dx.doi.org/10.1016/j.ymthe.2018.04.022] [PMID: 29778523]
[6]
Al-Ali H, Ding Y, Slepak T, et al. The mTOR substrate S6 kinase 1 (S6K1) is a negative regulator of axon regeneration and a potential drug target for central nervous system injury. J Neurosci 2017; 37(30): 7079-95.
[http://dx.doi.org/10.1523/JNEUROSCI.0931-17.2017] [PMID: 28626016]
[7]
Freire MA, Guimaraes JS, Santos JR, Simplício H, Gomes-Leal W. Morphometric analysis of NADPH diaphorase reactive neurons in a rat model of focal excitotoxic striatal injury. Neuropathology 2016; 36(6): 527-34.
[http://dx.doi.org/10.1111/neup.12311] [PMID: 27238870]
[8]
Falci SP, Indeck C, Lammertse DP. Posttraumatic spinal cord tethering and syringomyelia: surgical treatment and long-term outcome. J Neurosurg Spine 2009; 11(4): 445-60.
[http://dx.doi.org/10.3171/2009.4.SPINE09333] [PMID: 19929342]
[9]
Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL. Early management of severe traumatic brain injury. Lancet 2012; 380(9847): 1088-98.
[http://dx.doi.org/10.1016/S0140-6736(12)60864-2] [PMID: 22998718]
[10]
Bye N, Habgood MD, Callaway JK, et al. Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration. Exp Neurol 2007; 204(1): 220-33.
[http://dx.doi.org/10.1016/j.expneurol.2006.10.013] [PMID: 17188268]
[11]
Freire MA. Pathophysiology of neurodegeneration following traumatic brain injury. West Indian Med J 2012; 61(7): 751-5.
[PMID: 23620976]
[12]
Lopes RS, Cardoso MM, Sampaio AO, et al. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia. J Biosci 2016; 41(3): 381-94.
[http://dx.doi.org/10.1007/s12038-016-9621-1] [PMID: 27581930]
[13]
Wang YY, Shen D, Zhao LJ, Zeng N, Hu TH. Sting is a critical regulator of spinal cord injury by regulating microglial inflammation via interacting with TBK1 in mice. Biochem Biophys Res Commun 2019; 517(4): 741-8.
[http://dx.doi.org/10.1016/j.bbrc.2019.07.125] [PMID: 31400857]
[14]
Li XH, Fu NS, Xing ZM. MiR-100 suppresses inflammatory activation of microglia and neuronal apoptosis following spinal cord injury via TLR4/NF-κB pathway. Eur Rev Med Pharmacol Sci 2019; 23(20): 8713-20.
[PMID: 31696457]
[15]
Gensel JC, Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res 2015; 1619: 1-11.
[http://dx.doi.org/10.1016/j.brainres.2014.12.045] [PMID: 25578260]
[16]
Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity regeneration in the injured mouse spinal cord. J Neurosci 2009; 29(43): 13435-44.
[http://dx.doi.org/10.1523/JNEUROSCI.3257-09.2009] [PMID: 19864556]
[17]
Pineau I, Lacroix S. Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J Comp Neurol 2007; 500(2): 267-85.
[http://dx.doi.org/10.1002/cne.21149] [PMID: 17111361]
[18]
Zhao P, Chao W, Li W. FBXW5 reduction alleviates spinal cord injury (SCI) by blocking microglia activity: A mechanism involving p38 and JNK. Biochem Biophys Res Commun 2019; 514(2): 558-64.
[http://dx.doi.org/10.1016/j.bbrc.2019.04.086] [PMID: 31060780]
[19]
Lv R, Du L, Liu X, Zhou F, Zhang Z, Zhang L. Polydatin alleviates traumatic spinal cord injury by reducing microglial inflammation via regulation of iNOS and NLRP3 inflammasome pathway. Int Immunopharmacol 2019; 70: 28-36.
[http://dx.doi.org/10.1016/j.intimp.2019.02.006] [PMID: 30785088]
[20]
Zhu W, Chen X, Ning L, Jin K. Network analysis reveals TNF as a major hub of reactive inflammation following spinal cord injury. Sci Rep 2019; 9(1): 928.
[http://dx.doi.org/10.1038/s41598-018-37357-1] [PMID: 30700814]
[21]
Li H, Zhang X, Qi X, Zhu X, Cheng L. Icariin inhibits endoplasmic reticulum stress-induced neuronal apoptosis after spinal cord injury through modulating the PI3K/AKT signaling pathway. Int J Biol Sci 2019; 15(2): 277-86.
[http://dx.doi.org/10.7150/ijbs.30348] [PMID: 30745820]
[22]
Liu S, Sarkar C, Dinizo M, et al. Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death. Cell Death Dis 2015; 6e1582
[http://dx.doi.org/10.1038/cddis.2014.527] [PMID: 25569099]
[23]
Miao EA, Rajan JV, Aderem A. Caspase-1-induced pyroptotic cell death. Immunol Rev 2011; 243(1): 206-14.
[http://dx.doi.org/10.1111/j.1600-065X.2011.01044.x] [PMID: 21884178]
[24]
Ye Z, Zhang L, Li R, et al. Caspase-11 mediates pyroptosis of tubular epithelial cells and septic acute kidney injury. Kidney Blood Press Res 2019; 44(4): 465-78.
[http://dx.doi.org/10.1159/000499685] [PMID: 31230050]
[25]
de Rivero Vaccari JP, Bastien D, Yurcisin G, et al. P2X4 receptors influence inflammasome activation after spinal cord injury. J Neurosci 2012; 32(9): 3058-66.
[http://dx.doi.org/10.1523/JNEUROSCI.4930-11.2012] [PMID: 22378878]
[26]
de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci 2008; 28(13): 3404-14.
[http://dx.doi.org/10.1523/JNEUROSCI.0157-08.2008] [PMID: 18367607]
[27]
Song Z, Wang Z, Shen J, Xu S, Hu Z. Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats. Int J Nanomedicine 2017; 12: 1717-29.
[http://dx.doi.org/10.2147/IJN.S128848] [PMID: 28280337]
[28]
Ozturk AM, Sozbilen MC, Sevgili E, Dagci T, Özyalcin H, Armagan G. Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury. Injury 2018; 49(6): 1038-45.
[http://dx.doi.org/10.1016/j.injury.2018.03.021] [PMID: 29602490]
[29]
Hodgetts SI, Harvey AR. Neurotrophic factors used to treat spinal cord injury. Vitam Horm 2017; 104: 405-57.
[http://dx.doi.org/10.1016/bs.vh.2016.11.007] [PMID: 28215303]
[30]
Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer 2008; 8(2): 83-93.
[http://dx.doi.org/10.1038/nrc2290] [PMID: 18094723]
[31]
He J, Song Y, Li G, et al. Fbxw7 increases CCL2/7 in CX3CR1hi macrophages to promote intestinal inflammation. J Clin Invest 2019; 130: 3877-93.
[http://dx.doi.org/10.1172/JCI123374] [PMID: 31246581]
[32]
Wang R, Wang Y, Liu N, et al. FBW7 regulates endothelial functions by targeting KLF2 for ubiquitination and degradation. Cell Res 2013; 23(6): 803-19.
[http://dx.doi.org/10.1038/cr.2013.42] [PMID: 23507969]
[33]
Spruck CH, Strohmaier H, Sangfelt O, et al. hCDC4 gene mutations in endometrial cancer. Cancer Res 2002; 62(16): 4535-9.
[PMID: 12183400]
[34]
Balamurugan K, Sharan S, Klarmann KD, et al. FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4. Nat Commun 2013; 4: 1662.
[http://dx.doi.org/10.1038/ncomms2677] [PMID: 23575666]
[35]
Naruo S, Okajima K, Taoka Y, et al. Prostaglandin E1 reduces compression trauma-induced spinal cord injury in rats mainly by inhibiting neutrophil activation. J Neurotrauma 2003; 20(2): 221-8.
[http://dx.doi.org/10.1089/08977150360547125] [PMID: 12675974]
[36]
Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995; 12(1): 1-21.
[http://dx.doi.org/10.1089/neu.1995.12.1] [PMID: 7783230]
[37]
Li G, Cao Y, Shen F, et al. Mdivi-1 inhibits astrocyte activation and astroglial scar formation and enhances axonal regeneration after spinal cord injury in rats. Front Cell Neurosci 2016; 10: 241.
[http://dx.doi.org/10.3389/fncel.2016.00241] [PMID: 27807407]
[38]
Li HT, Zhao XZ, Zhang XR, et al. Exendin-4 enhances motor function recovery via promotion of autophagy and inhibition of neuronal apoptosis after spinal cord injury in rats. Mol Neurobiol 2016; 53(6): 4073-82.
[http://dx.doi.org/10.1007/s12035-015-9327-7] [PMID: 26198566]
[39]
Fei X, Bao W, Zhang P, et al. Inhalation of progesterone inhibits chronic airway inflammation of mice exposed to ozone. Mol Immunol 2017; 85: 174-84.
[http://dx.doi.org/10.1016/j.molimm.2017.02.006] [PMID: 28279894]
[40]
Allison DJ, Ditor DS. Immune dysfunction and chronic inflammation following spinal cord injury. Spinal Cord 2015; 53(1): 14-8.
[http://dx.doi.org/10.1038/sc.2014.184] [PMID: 25366531]
[41]
Xiao J, Zhang J, Zhao Y, et al. Sex differences of steroid receptor coactivator-1 expression after spinal cord injury in mice. Neurol Res 2017; 39(11): 1022-7.
[http://dx.doi.org/10.1080/01616412.2017.1367077] [PMID: 28816099]
[42]
Gaudet AD, Fonken LK, Ayala MT, et al. Spinal Cord Injury in Rats Disrupts the Circadian System. eNeuro 2018; 5(6): 5.
[http://dx.doi.org/10.1523/ENEURO.0328-18.2018] [PMID: 30627655]
[43]
Stephens KE, Chen Z, Sivanesan E, et al. RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation. Mol Pain 2018; 141744806918817429
[http://dx.doi.org/10.1177/1744806918817429] [PMID: 30451078]
[44]
Zhou Z, He C, Wang J. Regulation mechanism of Fbxw7-related signaling pathways (Review) Oncol Rep 2015; 34(5): 2215-24.
[http://dx.doi.org/10.3892/or.2015.4227] [PMID: 26324296]
[45]
Huang LY, Zhao J, Chen H, et al. SCFFBW7-mediated degradation of Brg1 suppresses gastric cancer metastasis. Nat Commun 2018; 9(1): 3569.
[http://dx.doi.org/10.1038/s41467-018-06038-y] [PMID: 30177679]
[46]
Yumimoto K, Akiyoshi S, Ueo H, et al. F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner. J Clin Invest 2015; 125(2): 621-35.
[http://dx.doi.org/10.1172/JCI78782] [PMID: 25555218]
[47]
Xu W, Taranets L, Popov N. Regulating Fbw7 on the road to cancer. Semin Cancer Biol 2016; 36: 62-70.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.005] [PMID: 26459133]
[48]
Cassavaugh JM, Hale SA, Wellman TL, Howe AK, Wong C. mediated degradation pathway during hypoxia. J Cell Biochem 2011; 112(12): 3882-90.
[http://dx.doi.org/10.1002/jcb.23321] [PMID: 21964756]
[49]
Merelli A, Rodríguez JCG, Folch J, Regueiro MR, Camins A, Lazarowski A. Understanding the role of hypoxia inducible factor during neurodegeneration for new therapeutics opportunities. Curr Neuropharmacol 2018; 16(10): 1484-98.
[http://dx.doi.org/10.2174/1570159X16666180110130253] [PMID: 29318974]
[50]
Kravchenko VV, Mathison JC, Schwamborn K, Mercurio F, Ulevitch RJ. IKKi/IKKepsilon plays a key role in integrating signals induced by pro-inflammatory stimuli. J Biol Chem 2003; 278(29): 26612-9.
[http://dx.doi.org/10.1074/jbc.M303001200] [PMID: 12736252]
[51]
David BT, Sampath S, Dong W, et al. A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury. J Neurotrauma 2014; 31(21): 1800-6.
[http://dx.doi.org/10.1089/neu.2014.3357] [PMID: 24936867]
[52]
Iannotti C, Ping Zhang Y, Shields CB, Han Y, Burke DA, Xu XM. A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury. Exp Neurol 2004; 189(2): 317-32.
[http://dx.doi.org/10.1016/j.expneurol.2004.05.033] [PMID: 15380482]
[53]
Puntambekar SS, Hinton DR, Yin X, et al. Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination. Glia 2015; 63(11): 2106-20.
[http://dx.doi.org/10.1002/glia.22880] [PMID: 26132901]
[54]
Nakanishi K, Nakasa T, Tanaka N, et al. Responses of microRNAs 124a and 223 following spinal cord injury in mice. Spinal Cord 2010; 48(3): 192-6.
[http://dx.doi.org/10.1038/sc.2009.89] [PMID: 19621023]
[55]
Lin Y, Vreman HJ, Wong RJ, Tjoa T, Yamauchi T, Noble-Haeusslein LJ. Heme oxygenase-1 stabilizes the blood-spinal cord barrier and limits oxidative stress and white matter damage in the acutely injured murine spinal cord. J Cereb Blood Flow Metab 2007; 27(5): 1010-21.
[http://dx.doi.org/10.1038/sj.jcbfm.9600412] [PMID: 17047682]
[56]
Kamencic H, Griebel RW, Lyon AW, Paterson PG, Juurlink BH. Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function. FASEB J 2001; 15(1): 243-50.
[http://dx.doi.org/10.1096/fj.00-0228com] [PMID: 11149912]
[57]
Das A, Guyton MK, Butler JT, Ray SK, Banik NL. Activation of calpain and caspase pathways in demyelination and neurodegeneration in animal model of multiple sclerosis. CNS Neurol Disord Drug Targets 2008; 7(3): 313-20.
[http://dx.doi.org/10.2174/187152708784936699] [PMID: 18673215]
[58]
Kaushal V, Dye R, Pakavathkumar P, et al. Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ 2015; 22(10): 1676-86.
[http://dx.doi.org/10.1038/cdd.2015.16] [PMID: 25744023]
[59]
Hertz NT, Adams EL, Weber RA, et al. Neuronally enriched RUFY3 is required for caspase-mediated axon degeneration. Neuron 2019; 103(3): 412-422.e4.
[http://dx.doi.org/10.1016/j.neuron.2019.05.030] [PMID: 31221560]
[60]
Gurney ME, Pu H, Chiu AY, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 1994; 264(5166): 1772-5. [Erratum in: Science 1995; 269: 149.
[http://dx.doi.org/10.1126/science.8209258] [PMID: 8209258]
[61]
Deng Y, Jiao C, Mi C, et al. Melatonin inhibits manganese-induced motor dysfunction and neuronal loss in mice: involvement of oxidative stress and dopaminergic neurodegeneration. Mol Neurobiol 2015; 51(1): 68-88.
[http://dx.doi.org/10.1007/s12035-014-8789-3] [PMID: 24969583]
[62]
Medeiros MS, Schumacher-Schuh A, Cardoso AM, et al. Iron and oxidative stress in Parkinson’s Disease: an observational study of injury biomarkers. PLoS One 2016; 11(1)e0146129
[http://dx.doi.org/10.1371/journal.pone.0146129] [PMID: 26751079]
[63]
Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 2015; 526(7575): 660-5.
[http://dx.doi.org/10.1038/nature15514] [PMID: 26375003]
[64]
Mortezaee K, Khanlarkhani N, Beyer C, Zendedel A. Inflammasome: Its role in traumatic brain and spinal cord injury. J Cell Physiol 2018; 233(7): 5160-9.
[http://dx.doi.org/10.1002/jcp.26287] [PMID: 29150951]
[65]
Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 2015; 526(7575): 666-71.
[http://dx.doi.org/10.1038/nature15541] [PMID: 26375259]
[66]
Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 2015; 265(1): 130-42.
[http://dx.doi.org/10.1111/imr.12287] [PMID: 25879289]
[67]
Xiao J, Wang C, Yao JC, et al. Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice. PLoS Biol 2018; 16(11)e3000047
[http://dx.doi.org/10.1371/journal.pbio.3000047] [PMID: 30388107]
[68]
Rathinam VAK, Zhao Y, Shao F. Innate immunity to intracellular LPS. Nat Immunol 2019; 20(5): 527-33.
[http://dx.doi.org/10.1038/s41590-019-0368-3] [PMID: 30962589]
[69]
Scholpa NE, Schnellmann RG. Mitochondrial-based therapeutics for the treatmentof spinal cord injury: mitochondrial biogenesis as a potential pharmacological target. J Pharmacol Exp Ther 2017; 363(3): 303-13.
[http://dx.doi.org/10.1124/jpet.117.244806] [PMID: 28935700]
[70]
Yang Y, Ye Y, Kong C, et al. MiR-124 Enriched exosomes promoted the M2 polarization of microglia and enhanced hippocampus neurogenesis after traumatic brain injury by inhibiting TLR4 pathway. Neurochem Res 2019; 44(4): 811-28.
[http://dx.doi.org/10.1007/s11064-018-02714-z] [PMID: 30628018]
[71]
Song Y, Hu M, Zhang J, Teng ZQ, Chen C. A novel mechanism of synaptic and cognitive impairments mediated via microRNA-30b in Alzheimer’s disease. EBioMedicine 2019; 39: 409-21.
[http://dx.doi.org/10.1016/j.ebiom.2018.11.059] [PMID: 30522932]
[72]
Cava C, Manna I, Gambardella A, Bertoli G, Castiglioni I. Potential role of miRNAs as theranostic biomarkers of epilepsy. Mol Ther Nucleic Acids 2018; 13: 275-90.
[http://dx.doi.org/10.1016/j.omtn.2018.09.008] [PMID: 30321815]
[73]
Fuller-Carter PI, Carter KW, Anderson D, Harvey AR, Giles KM, Rodger J. Integrated analyses of zebrafish miRNA and mRNA expression profiles identify miR-29b and miR-223 as potential regulators of optic nerve regeneration. BMC Genomics 2015; 16: 591.
[http://dx.doi.org/10.1186/s12864-015-1772-1] [PMID: 26265132]
[74]
Shin JH, Park YM, Kim DH, et al. Ischemic brain extract increases SDF-1 expression in astrocytes through the CXCR2/miR-223/miR-27b pathway. Biochim Biophys Acta 2014; 1839(9): 826-36.
[http://dx.doi.org/10.1016/j.bbagrm.2014.06.019] [PMID: 24999035]
[75]
Liu D, Huang Y, Jia C, Li Y, Liang F, Fu Q. Administration of antagomir-223 inhibits apoptosis, promotes angiogenesis and functional recovery in rats with spinal cord injury. Cell Mol Neurobiol 2015; 35(4): 483-91.
[http://dx.doi.org/10.1007/s10571-014-0142-x] [PMID: 25416533]

Rights & Permissions Print Cite
Article Metrics
13
1
© 2024 Bentham Science Publishers | Privacy Policy