Skip to main content

Advertisement

SpringerLink
Log in

Topotecan Reduces Neuron Death after Spinal Cord Injury by Suppressing Caspase-1-Dependent Pyroptosis

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

A Correction to this article was published on 30 September 2022

This article has been updated

Abstract

Neuronal loss and excessive inflammatory response mediate the pathogenesis of spinal cord injury (SCI). Topotecan (TPT), a topoisomerase 1 (Top 1) inhibitor, is recently revealed to control lethal inflammation. Top 1 is an essential enzyme in mammalian cells and acts as a key role in the DNA replication, transcription, and repair. However, the effects and underlying mechanisms of TPT in SCI remain unclear. Here, we report that topotecan (TPT), a Top 1 inhibitor, led to a significant recovery of hindlimb locomotor function in mice. Moreover, TPT reduced Top 1 level, prevented nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome activation, reduced caspase-1 expression and pyroptosis, and decreased the levels of pro-inflammatory cytokines and the number of neutrophils in mice. Furthermore, TPT suppressed NLRP3 inflammasome activation, diminished caspase-1 expression and pyroptosis, and reduced pro-inflammatory cytokines levels in neurons. In addition, inhibition of caspase-1 by VX-765 inhibited pyroptosis and reduced proinflammatory cytokine levels in mice. Furthermore, administration of VX-765 suppressed pyroptosis and alleviated cell damage in primary cultured neurons. Our findings suggest that TPT with specific dose and duration reduces neuron death and improves functional recovery after SCI presumably depends on inhibition of caspase-1-dependent pyroptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

All data is real and guarantees the validity of experimental results.

Change history

References

  1. Fu H, Hu D, Zhang L, Shen X, Tang P (2018) Efficacy of oligodendrocyte progenitor cell transplantation in rat models with traumatic thoracic spinal cord injury: a systematic review and meta-analysis. J Neurotrauma 35(21):2507–2518. https://doi.org/10.1089/neu.2017.5606

    Article  PubMed  Google Scholar 

  2. Kijima K, Kubota K, Hara M, Kobayakawa K, Yokota K, Saito T, Yoshizaki S, Maeda T et al (2019) The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury. EBioMedicine 41:659–669. https://doi.org/10.1016/j.ebiom.2019.03.003

    Article  PubMed  PubMed Central  Google Scholar 

  3. Quadri SA, Farooqui M, Ikram A, Zafar A, Khan MA, Suriya SS, Claus CF, Fiani B et al (2020) Recent update on basic mechanisms of spinal cord injury. Neurosurg Rev 43(2):425–441. https://doi.org/10.1007/s10143-018-1008-3

    Article  PubMed  Google Scholar 

  4. Yoshizaki S, Kijima K, Hara M, Saito T, Tamaru T, Tanaka M, Konno DJ, Nakashima Y et al (2019) Tranexamic acid reduces heme cytotoxicity via the TLR4/TNF axis and ameliorates functional recovery after spinal cord injury. J Neuroinflamm 16(1):160. https://doi.org/10.1186/s12974-019-1536-y

    Article  CAS  Google Scholar 

  5. Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG (2017) Traumatic spinal cord injury. Nat Rev Dis Primers 3:17018. https://doi.org/10.1038/nrdp.2017.18

    Article  PubMed  Google Scholar 

  6. Lago N, Pannunzio B, Amo-Aparicio J, Lopez-Vales R, Peluffo H (2018) CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1. Brain Behav Immun 73:416–426. https://doi.org/10.1016/j.bbi.2018.06.002

    Article  CAS  PubMed  Google Scholar 

  7. Yates AG, Jogia T, Gillespie ER, Couch Y, Ruitenberg MJ, Anthony DC (2021) Acute IL-1RA treatment suppresses the peripheral and central inflammatory response to spinal cord injury. J Neuroinflamm 18(1):15. https://doi.org/10.1186/s12974-020-02050-6

    Article  CAS  Google Scholar 

  8. Zhang S, Fujita Y, Matsuzaki R, Yamashita T (2018) Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury. Cell Death Dis 9(5):460. https://doi.org/10.1038/s41419-018-0543-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mazzone GL, Veeraraghavan P, Gonzalez-Inchauspe C, Nistri A, Uchitel OD (2017) ASIC channel inhibition enhances excitotoxic neuronal death in an in vitro model of spinal cord injury. Neuroscience 343:398–410. https://doi.org/10.1016/j.neuroscience.2016.12.008

    Article  CAS  PubMed  Google Scholar 

  10. Namjoo Z, Mortezaee K, Joghataei MT, Moradi F, Piryaei A, Abbasi Y, Hosseini A, Majidpoor J (2018) Targeting axonal degeneration and demyelination using combination administration of 17beta-estradiol and Schwann cells in the rat model of spinal cord injury. J Cell Biochem 119(12):10195–10203. https://doi.org/10.1002/jcb.27361

    Article  CAS  PubMed  Google Scholar 

  11. Prow NA, Irani DN (2008) The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis. J Neurochem 105(4):1276–1286. https://doi.org/10.1111/j.1471-4159.2008.05230.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pei JP, Fan LH, Nan K, Li J, Dang XQ, Wang KZ (2017) HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury. J Neuroinflamm 14(1):97. https://doi.org/10.1186/s12974-017-0870-1

    Article  CAS  Google Scholar 

  13. Li X, Yu Z, Zong W, Chen P, Li J, Wang M, Ding F, Xie M et al (2020) Deficiency of the microglial Hv1 proton channel attenuates neuronal pyroptosis and inhibits inflammatory reaction after spinal cord injury. J Neuroinflamm 17(1):263. https://doi.org/10.1186/s12974-020-01942-x

    Article  CAS  Google Scholar 

  14. Wu J, Lin S, Wan B, Velani B, Zhu Y (2019) Pyroptosis in liver disease: new insights into disease mechanisms. Aging Dis 10(5):1094–1108. https://doi.org/10.14336/AD.2019.0116

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kai J, Yang X, Wang Z, Wang F, Jia Y, Wang S, Tan S, Chen A et al (2020) Oroxylin a promotes PGC-1alpha/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease. Free Radic Biol Med 153:89–102. https://doi.org/10.1016/j.freeradbiomed.2020.03.031

    Article  CAS  PubMed  Google Scholar 

  16. Zhang D, Qian J, Zhang P, Li H, Shen H, Li X, Chen G (2019) Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro. J Neurosci Res 97(6):645–660. https://doi.org/10.1002/jnr.24385

    Article  CAS  PubMed  Google Scholar 

  17. Wang S, Yuan YH, Chen NH, Wang HB (2019) The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson’s disease. Int Immunopharmacol 67:458–464. https://doi.org/10.1016/j.intimp.2018.12.019

    Article  CAS  PubMed  Google Scholar 

  18. McKenzie BA, Mamik MK, Saito LB, Boghozian R, Monaco MC, Major EO, Lu JQ, Branton WG et al (2018) Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proc Natl Acad Sci U S A 115(26):E6065–E6074. https://doi.org/10.1073/pnas.1722041115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Meng Q, Li Y, Ji T, Chao Y, Li J, Fu Y, Wang S, Chen Q et al (2021) Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor alpha-mediated autophagy. J Adv Res 28:149–164. https://doi.org/10.1016/j.jare.2020.08.010

    Article  CAS  PubMed  Google Scholar 

  20. Zheng G, Zhan Y, Wang H, Luo Z, Zheng F, Zhou Y, Wu Y, Wang S et al (2019) Carbon monoxide releasing molecule-3 alleviates neuron death after spinal cord injury via inflammasome regulation. EBioMedicine 40:643–654. https://doi.org/10.1016/j.ebiom.2018.12.059

    Article  PubMed  PubMed Central  Google Scholar 

  21. Liu W, Chen Y, Meng J, Wu M, Bi F, Chang C, Li H, Zhang L (2018) Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo. J Neuroinflamm 15(1):48. https://doi.org/10.1186/s12974-018-1083-y

    Article  CAS  Google Scholar 

  22. Al Mamun A, Wu Y, Monalisa I, Jia C, Zhou K, Munir F, Xiao J (2021) Role of pyroptosis in spinal cord injury and its therapeutic implications. J Adv Res 28:97–109. https://doi.org/10.1016/j.jare.2020.08.004

    Article  CAS  PubMed  Google Scholar 

  23. Ho JSY, Mok BW, Campisi L, Jordan T, Yildiz S, Parameswaran S, Wayman JA, Gaudreault NN et al (2021) TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation. Cell 184(10):2618-2632 e2617. https://doi.org/10.1016/j.cell.2021.03.051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rialdi A, Campisi L, Zhao N, Lagda AC, Pietzsch C, Ho JSY, Martinez-Gil L, Fenouil R et al (2016) Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation. Science 352(6289):aad7993. https://doi.org/10.1126/science.aad7993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Syrios J, Kouroussis C, Kotsakis A, Kentepozidis N, Kontopodis E, Kalbakis K, Vardakis N, Hatzidaki D et al (2019) Combination of weekly topotecan and gemcitabine as a salvage treatment in patients with recurrent ovarian cancer: a phase I study. Minerva Ginecol 71(3):182–190. https://doi.org/10.23736/S0026-4784.19.04249-7

    Article  PubMed  Google Scholar 

  26. Ernani V, Jahan R, Smith LM, Marr AS, Kimbrough SE, Kos ME, Tijerina J, Pivovar S et al (2020) A phase I study of weekly doxorubicin and oral topotecan for patients with relapsed or refractory small cell lung cancer (SCLC): a Fred and Pamela buffet Cancer Center clinical trials network study. Cancer Treat Res Commun 22:100162. https://doi.org/10.1016/j.ctarc.2019.100162

    Article  PubMed  Google Scholar 

  27. Rujkijyanont P, Photia A, Traivaree C, Monsereenusorn C, Anurathapan U, Seksarn P, Sosothikul D, Techavichit P et al (2019) Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study. BMC Cancer 19(1):961. https://doi.org/10.1186/s12885-019-6186-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Riedlinger T, Bartkuhn M, Zimmermann T, Hake SB, Nist A, Stiewe T, Kracht M, Schmitz ML (2019) Chemotherapeutic drugs inhibiting topoisomerase 1 activity impede cytokine-induced and NF-kappaB p65-regulated gene expression. Cancers (Basel) 11(6). https://doi.org/10.3390/cancers11060883

  29. Yuin Ho JS, Wing-Yee Mok B, Campisi L, Jordan T, Yildiz S, Parameswaran S, Wayman JA, Gaudreault NN et al (2020) Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models. bioRxiv. https://doi.org/10.1101/2020.12.01.404483

  30. Wan B, Xu WJ, Zhan P, Jin JJ, Xi GM, Chen MZ, Hu YB, Zhu SH et al (2018) Topotecan alleviates ventilator-induced lung injury via NF-kappaB pathway inhibition. Cytokine 110:381–388. https://doi.org/10.1016/j.cyto.2018.04.016

    Article  CAS  PubMed  Google Scholar 

  31. Shekhar S, Vatsa N, Kumar V, Singh BK, Jamal I, Sharma A, Jana NR (2017) Topoisomerase 1 inhibitor topotecan delays the disease progression in a mouse model of Huntington’s disease. Hum Mol Genet 26(2):420–429. https://doi.org/10.1093/hmg/ddw398

    Article  CAS  PubMed  Google Scholar 

  32. Kunimi H, Miwa Y, Katada Y, Tsubota K, Kurihara T (2019) HIF inhibitor topotecan has a neuroprotective effect in a murine retinal ischemia-reperfusion model. PeerJ 7:e7849. https://doi.org/10.7717/peerj.7849

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhang D, Xuan J, Zheng BB, Zhou YL, Lin Y, Wu YS, Zhou YF, Huang YX et al (2017) Metformin improves functional recovery after spinal cord injury via autophagy flux stimulation. Mol Neurobiol 54(5):3327–3341. https://doi.org/10.1007/s12035-016-9895-1

    Article  CAS  PubMed  Google Scholar 

  34. Paterniti I, Impellizzeri D, Di Paola R, Esposito E, Gladman S, Yip P, Priestley JV, Michael-Titus AT et al (2014) Docosahexaenoic acid attenuates the early inflammatory response following spinal cord injury in mice: in-vivo and in-vitro studies. J Neuroinflamm 11:6. https://doi.org/10.1186/1742-2094-11-6

    Article  CAS  Google Scholar 

  35. Yang XM, Downey JM, Cohen MV, Housley NA, Alvarez DF, Audia JP (2017) The highly selective caspase-1 inhibitor VX-765 provides additive protection against myocardial infarction in rat hearts when combined with a platelet inhibitor. J Cardiovasc Pharmacol Ther 22(6):574–578. https://doi.org/10.1177/1074248417702890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Jiang W, Li M, He F, Zhou S, Zhu L (2017) Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice. J Neuroinflamm 14(1):207. https://doi.org/10.1186/s12974-017-0980-9

    Article  CAS  Google Scholar 

  37. Zendedel A, Johann S, Mehrabi S, Joghataei MT, Hassanzadeh G, Kipp M, Beyer C (2016) Activation and regulation of NLRP3 inflammasome by intrathecal application of SDF-1a in a spinal cord injury model. Mol Neurobiol 53(5):3063–3075. https://doi.org/10.1007/s12035-015-9203-5

    Article  CAS  PubMed  Google Scholar 

  38. Basso DM, Fisher LC, Anderson AJ, Jakeman LB, McTigue DM, Popovich PG (2006) Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J Neurotrauma 23(5):635–659. https://doi.org/10.1089/neu.2006.23.635

    Article  PubMed  Google Scholar 

  39. Francos-Quijorna I, Santos-Nogueira E, Gronert K, Sullivan AB, Kopp MA, Brommer B, David S, Schwab JM et al (2017) Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after spinal cord injury. J Neurosci 37(48):11731–11743. https://doi.org/10.1523/JNEUROSCI.1395-17.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Slaets H, Nelissen S, Janssens K, Vidal PM, Lemmens E, Stinissen P, Hendrix S, Hellings N (2014) Oncostatin M reduces lesion size and promotes functional recovery and neurite outgrowth after spinal cord injury. Mol Neurobiol 50(3):1142–1151. https://doi.org/10.1007/s12035-014-8795-5

    Article  CAS  PubMed  Google Scholar 

  41. Yu D, Li M, Nie P, Ni B, Zhang Z, Zhou Y (2018) Bcl-2/E1B-19KD-interacting protein 3/light chain 3 interaction induces mitophagy in spinal cord injury in rats both in vivo and in vitro. J Neurotrauma 35(18):2183–2194. https://doi.org/10.1089/neu.2017.5280

    Article  PubMed  Google Scholar 

  42. Lu Y, Xu S, Chen H, He M, Deng Y, Cao Z, Pi H, Chen C et al (2016) CdSe/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation. Biomaterials 90:27–39. https://doi.org/10.1016/j.biomaterials.2016.03.003

    Article  CAS  PubMed  Google Scholar 

  43. de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW (2008) A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci 28(13):3404–3414. https://doi.org/10.1523/JNEUROSCI.0157-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lu F, Lan Z, Xin Z, He C, Guo Z, Xia X, Hu T (2020) Emerging insights into molecular mechanisms underlying pyroptosis and functions of inflammasomes in diseases. J Cell Physiol 235(4):3207–3221. https://doi.org/10.1002/jcp.29268

    Article  CAS  PubMed  Google Scholar 

  45. Boato F, Rosenberger K, Nelissen S, Geboes L, Peters EM, Nitsch R, Hendrix S (2013) Absence of IL-1beta positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury. J Neuroinflamm 10:6. https://doi.org/10.1186/1742-2094-10-6

    Article  CAS  Google Scholar 

  46. Li T, Li YT, Song DY (2018) The expression of IL-1beta can deteriorate the prognosis of nervous system after spinal cord injury. Int J Neurosci 128(8):778–782. https://doi.org/10.1080/00207454.2018.1424154

    Article  CAS  PubMed  Google Scholar 

  47. Oliveira SH, Canetti C, Ribeiro RA, Cunha FQ (2008) Neutrophil migration induced by IL-1beta depends upon LTB4 released by macrophages and upon TNF-alpha and IL-1beta released by mast cells. Inflammation 31(1):36–46. https://doi.org/10.1007/s10753-007-9047-x

    Article  CAS  PubMed  Google Scholar 

  48. Oleszycka E, Moran HB, Tynan GA, Hearnden CH, Coutts G, Campbell M, Allan SM, Scott CJ et al (2016) IL-1alpha and inflammasome-independent IL-1beta promote neutrophil infiltration following alum vaccination. FEBS J 283(1):9–24. https://doi.org/10.1111/febs.13546

    Article  CAS  PubMed  Google Scholar 

  49. Burke SJ, Lu D, Sparer TE, Karlstad MD, Collier JJ (2014) Transcription of the gene encoding TNF-alpha is increased by IL-1beta in rat and human islets and beta-cell lines. Mol Immunol 62(1):54–62. https://doi.org/10.1016/j.molimm.2014.05.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ledesma E, Martinez I, Cordova Y, Rodriguez-Sosa M, Monroy A, Mora L, Soto I, Ramos G et al (2004) Interleukin-1 beta (IL-1beta) induces tumor necrosis factor alpha (TNF-alpha) expression on mouse myeloid multipotent cell line 32D cl3 and inhibits their proliferation. Cytokine 26(2):66–72. https://doi.org/10.1016/j.cyto.2003.12.009

    Article  CAS  PubMed  Google Scholar 

  51. Zhou W, Yuan T, Gao Y, Yin P, Liu W, Pan C, Liu Y, Yu X (2017) IL-1beta-induces NF-kappaB and upregulates microRNA-372 to inhibit spinal cord injury recovery. J Neurophysiol 117(6):2282–2291. https://doi.org/10.1152/jn.00936.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lin WP, Lin JH, Cai B, Shi JX, Li WJ, Choudhury GR, Wu SQ, Wu JZ et al (2016) Effect of adenovirus-mediated RNA interference of IL-1beta expression on spinal cord injury in rats. Spinal Cord 54(10):778–784. https://doi.org/10.1038/sc.2016.20

    Article  PubMed  Google Scholar 

  53. Lin XL, Zhu J, Wang LM, Yan F, Sha WP, Yang HL (2019) MiR-92b-5p inhibitor suppresses IL-18 mediated inflammatory amplification after spinal cord injury via IL-18BP up-regulation. Eur Rev Med Pharmacol Sci 23(5):1891–1898. https://doi.org/10.26355/eurrev_201903_17226

    Article  PubMed  Google Scholar 

  54. Jorgensen I, Lopez JP, Laufer SA, Miao EA (2016) IL-1beta, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. Eur J Immunol 46(12):2761–2766. https://doi.org/10.1002/eji.201646647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. McKenzie BA, Dixit VM, Power C (2020) Fiery cell death: pyroptosis in the central nervous system. Trends Neurosci 43(1):55–73. https://doi.org/10.1016/j.tins.2019.11.005

    Article  CAS  PubMed  Google Scholar 

  56. Hsieh H, Vignesh KS, Deepe GS Jr, Choubey D, Shertzer HG, Genter MB (2016) Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora. Toxicol In Vitro 35:24–30. https://doi.org/10.1016/j.tiv.2016.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chen S, Zhou C, Yu H, Tao L, An Y, Zhang X, Wang Y, Wang Y et al (2019) 27-Hydroxycholesterol contributes to lysosomal membrane permeabilization-mediated pyroptosis in co-cultured SH-SY5Y cells and C6 Cells. Front Mol Neurosci 12:14. https://doi.org/10.3389/fnmol.2019.00014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhu S, Zhang Z, Jia LQ, Zhan KX, Wang LJ, Song N, Liu Y, Cheng YY et al (2019) Valproic acid attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-pyroptosis pathways. Neurochem Int 124:141–151. https://doi.org/10.1016/j.neuint.2019.01.003

    Article  CAS  PubMed  Google Scholar 

  59. Yang Z, Liang C, Wang T, Zou Q, Zhou M, Cheng Y, Peng H, Ji Z et al (2020) NLRP3 inflammasome activation promotes the development of allergic rhinitis via epithelium pyroptosis. Biochem Biophys Res Commun 522(1):61–67. https://doi.org/10.1016/j.bbrc.2019.11.031

    Article  CAS  PubMed  Google Scholar 

  60. Liu YG, Chen JK, Zhang ZT, Ma XJ, Chen YC, Du XM, Liu H, Zong Y et al (2017) NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages. Cell Death Dis 8(2):e2579. https://doi.org/10.1038/cddis.2016.460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Liu T, Zhou YT, Wang LQ, Li LY, Bao Q, Tian S, Chen MX, Chen HX et al (2019) NOD-like receptor family, pyrin domain containing 3 (NLRP3) contributes to inflammation, pyroptosis, and mucin production in human airway epithelium on rhinovirus infection. J Allergy Clin Immunol 144(3):777-787 e779. https://doi.org/10.1016/j.jaci.2019.05.006

    Article  CAS  PubMed  Google Scholar 

  62. Sun W, Lu H, Lyu L, Yang P, Lin Z, Li L, Sun L, Lu D (2019) Gastrodin ameliorates microvascular reperfusion injury-induced pyroptosis by regulating the NLRP3/caspase-1 pathway. J Physiol Biochem 75(4):531–547. https://doi.org/10.1007/s13105-019-00702-7

    Article  CAS  PubMed  Google Scholar 

  63. Fan Y, Du L, Fu Q, Zhou Z, Zhang J, Li G, Wu J (2018) Inhibiting the NLRP3 inflammasome with MCC950 ameliorates isoflurane-induced pyroptosis and cognitive impairment in aged mice. Front Cell Neurosci 12:426. https://doi.org/10.3389/fncel.2018.00426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhang Y, Liu X, Bai X, Lin Y, Li Z, Fu J, Li M, Zhao T et al (2018) Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis. J Pineal Res 64(2). https://doi.org/10.1111/jpi.12449

  65. Kouzine F, Gupta A, Baranello L, Wojtowicz D, Ben-Aissa K, Liu J, Przytycka TM, Levens D (2013) Transcription-dependent dynamic supercoiling is a short-range genomic force. Nat Struct Mol Biol 20(3):396–403. https://doi.org/10.1038/nsmb.2517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jin J, Xu W, Wan B, Wang X, Zhou Z, Miao Y, Lv T, Song Y (2019) Topotecan alleviates lipopolysaccharide-mediated acute lung injury via the NF-kappaB signaling pathway. J Surg Res 235:83–92. https://doi.org/10.1016/j.jss.2018.08.057

    Article  CAS  PubMed  Google Scholar 

  67. Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454(7203):428–435. https://doi.org/10.1038/nature07201

    Article  CAS  PubMed  Google Scholar 

  68. Kotas ME, Medzhitov R (2015) Homeostasis, inflammation, and disease susceptibility. Cell 160(5):816–827. https://doi.org/10.1016/j.cell.2015.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wang X, Oates JC, Helke KL, Gilkeson GS, Zhang XK (2021) Camptothecin and topotecan, inhibitors of transcription factor Fli-1 and topoisomerase, markedly ameliorate lupus nephritis in (NZB x NZW)F1 mice and reduce the production of inflammatory mediators in human renal cells. Arthritis Rheumatol 73(8):1478–1488. https://doi.org/10.1002/art.41685

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the support by the funding of Zhejiang Provincial Public Welfare Research Project (grant. LGF20H060014), Zhejiang Provincial Medical and Health Technology Project (grant. 2020KY699), Young Talents Cultivation Program of Hangzhou First People’s Hospital (grant. YQNYC202136).

Funding

This work was supported by Zhejiang Provincial Public Welfare Research Project (grant. LGF20H060014), Zhejiang Provincial Medical and Health Technology Project (grant. 2020KY699), and Young Talents Cultivation Program of Hangzhou First People’s Hospital (grant. YQNYC202136).

Author information

Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang, China

    Wu Jiang & Junsong Wu

  2. Department of Orthopedics, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No.261 Huansha Road, Shangcheng District, Hangzhou, 310006, Zhejiang, China

    Wu Jiang, Fan He & Guoming Ding

Authors
  1. Wu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fan He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guoming Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junsong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Wu Jiang and Junsong Wu wrote the paper. Wu Jiang and Fan He performed the experiments. Guoming Ding analyzed the data. Junsong Wu and Wu Jiang designed the research and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Junsong Wu.

Ethics declarations

Ethics Approval

Procedures were carried out in accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Ethical Committee of the Hangzhou First People’s Hospital’s cooperative animal experiment center.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, W., He, F., Ding, G. et al. Topotecan Reduces Neuron Death after Spinal Cord Injury by Suppressing Caspase-1-Dependent Pyroptosis. Mol Neurobiol 59, 6033–6048 (2022). https://doi.org/10.1007/s12035-022-02960-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-022-02960-x

Keywords

Search

Navigation