Abstract
Tripartite motif-containing 22 (TRIM22) has been documented to participate in numerous cellular activities during human diseases. However, whether TRIM22 is involved in the regulation of neuronal survival during the progression of cerebral ischemia/reperfusion (I/R) injury remains unknown. In the present study, treatment of HCN-2 cells with oxygen–glucose deprivation/reoxygenation (OGD/R) markedly upregulated TRIM22 expression. A significant increase in TRIM22 expression was observed in the ischemic cortex tissues from middle cerebral artery occlusion/reperfusion mice. OGD/R inhibited the viability and induced the apoptosis of HCN-2 cells, which was accompanied by an increase in caspase-3 activity and an increase in LDH release. Furthermore, OGD/R increased the levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemoattractant protein-1 and induced NLRP3 inflammasome activation, as evidenced by increases in NACHT, LRR and PYD domains-containing protein 3, apoptosis-associated speck-like protein containing a caspase recruitment domain and cleaved caspase-1 expression and caspase-1 activity. However, these changes induced by OGD/R were blocked by silencing of TRIM22. In addition, TRIM22 regulated NF-κB activity in HCN-2 cells undergoing OGD/R stimulation. Furthermore, inhibition of NF-κB by pyrrolidine dithiocarbamate inhibited OGD/R-induced NLRP3 inflammasome activation in HCN-2 cells. Taken together, silencing of TRIM22 protects neurons against OGD/R-induced apoptosis and inflammation. The anti-inflammatory effect of TRIM22 knockdown was the consequence of inhibition of NF-κB/NLRP3 axis. TRIM22 may be a potential target for treating cerebral I/R injury.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- TRIM22:
-
Tripartite motif-containing 22
- I/R:
-
Ischemia/reperfusion
- LDH:
-
Lactate dehydrogenase
- NF-κB:
-
Nuclear factor-κB
- OGD/R:
-
Oxygen–glucose deprivation/reoxygenation
- TNF-α:
-
Tumor necrosis factor-alpha
- IL-1β:
-
Interleukin-1 beta
- NLRP3:
-
Nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3
References
Basso FG, Pansani TN, Turrioni AP, Soares DG, de Souza Costa CA, Hebling J (2016) Tumor necrosis factor-alpha and interleukin (IL)-1beta, IL-6, and IL-8 impair in vitro migration and induce apoptosis of gingival fibroblasts and epithelial cells, delaying wound healing. J Periodontol 87(8):990–996. https://doi.org/10.1902/jop.2016.150713
Carotenuto M, Pedone E, Diana D, de Antonellis P, Dzeroski S, Marino N, Navas L, Di Dato V, Scoppettuolo MN, Cimmino F, Correale S, Pirone L, Monti SM, Bruder E, Zenko B, Slavkov I, Pastorino F, Ponzoni M, Schulte JH, Schramm A, Eggert A, Westermann F, Arrigoni G, Accordi B, Basso G, Saviano M, Fattorusso R, Zollo M (2013) Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction. Sci Rep 3:1351. https://doi.org/10.1038/srep01351
Chen C, Zhao D, Fang S, Chen Q, Cheng B, Fang X, Shu Q (2017) TRIM22-mediated apoptosis is associated with bak oligomerization in monocytes. Sci Rep 7:39961. https://doi.org/10.1038/srep39961
D'Ignazio L, Bandarra D, Rocha S (2016) NF-kappaB and HIF crosstalk in immune responses. FEBS J 283(3):413–424. https://doi.org/10.1111/febs.13578
Davis GM, Low WY, Anderson JWT, Boag PR (2017) Exploring potential germline-associated roles of the TRIM-NHL protein NHL-2 through RNAi screening. G3 (Bethesda, Md) 7(10):3251–3256. https://doi.org/10.1534/g3.117.300166
Dziedzic T (2015) Systemic inflammation as a therapeutic target in acute ischemic stroke. Expert Rev Neurother 15(5):523–531. https://doi.org/10.1586/14737175.2015.1035712
Elliott EI, Sutterwala FS (2015) Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunol Rev 265(1):35–52. https://doi.org/10.1111/imr.12286
Esposito D, Koliopoulos MG, Rittinger K (2017) Structural determinants of TRIM protein function. Biochem Soc Trans 45(1):183–191. https://doi.org/10.1042/bst20160325
Fann DY, Lim YA, Cheng YL, Lok KZ, Chunduri P, Baik SH, Drummond GR, Dheen ST, Sobey CG, Jo DG, Chen CL, Arumugam TV (2018) Evidence that NF-kappaB and MAPK Signaling promotes NLRP inflammasome activation in neurons following ischemic stroke. Mol Neurobiol 55(2):1082–1096. https://doi.org/10.1007/s12035-017-0394-9
Gao L, Dong Q, Song Z, Shen F, Shi J, Li Y (2017) NLRP3 inflammasome: a promising target in ischemic stroke. Inflamm Res 66(1):17–24. https://doi.org/10.1007/s00011-016-0981-7
Guell K, Bix GJ (2014) Brain endothelial cell specific integrins and ischemic stroke. Expert Rev Neurother 14(11):1287–1292. https://doi.org/10.1586/14737175.2014.964210
Han K, Lou DI, Sawyer SL (2011) Identification of a genomic reservoir for new TRIM genes in primate genomes. PLoS Genet 7(12):e1002388. https://doi.org/10.1371/journal.pgen.1002388
Hatakeyama S (2017) TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci 42(4):297–311. https://doi.org/10.1016/j.tibs.2017.01.002
Li L, Qi Y, Ma X, Xiong G, Wang L, Bao C (2018) TRIM22 knockdown suppresses chronic myeloid leukemia via inhibiting PI3K/Akt/mTOR signaling pathway. Cell Biol Int 42(9):1192–1199. https://doi.org/10.1002/cbin.10989
Li Q, Lee CH, Peters LA, Mastropaolo LA, Thoeni C, Elkadri A, Schwerd T, Zhu J, Zhang B, Zhao Y, Hao K, Dinarzo A, Hoffman G, Kidd BA, Murchie R, Al Adham Z, Guo C, Kotlarz D, Cutz E, Walters TD, Shouval DS, Curran M, Dobrin R, Brodmerkel C, Snapper SB, Klein C, Brumell JH, Hu M, Nanan R, Snanter-Nanan B, Wong M, Le Deist F, Haddad E, Roifman CM, Deslandres C, Griffiths AM, Gaskin KJ, Uhlig HH, Schadt EE, Muise AM (2016) Variants in TRIM22 that affect NOD2 signaling are associated with very-early-onset inflammatory bowel disease. Gastroenterology 150(5):1196–1207. https://doi.org/10.1053/j.gastro.2016.01.031
Meroni G (2012) Genomics and evolution of the TRIM gene family. Adv Exp Med Biol 770:1–9. https://doi.org/10.1007/978-1-4614-5398-7_1
Obad S, Olofsson T, Mechti N, Gullberg U, Drott K (2007) Regulation of the interferon-inducible p53 target gene TRIM22 (Staf50) in human T lymphocyte activation. J Interferon Cytokine Res 27(10):857–864. https://doi.org/10.1089/jir.2006.0180
Oteiza A, Mechti N (2015) Control of FoxO4 activity and cell survival by TRIM22 Directs TLR3-stimulated cells toward IFN Type I gene induction or apoptosis. J Interferon Cytokine Res 35(11):859–874. https://doi.org/10.1089/jir.2015.0020
Ozato K, Shin DM, Chang TH, Morse HC 3rd (2008) TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol 8(11):849–860. https://doi.org/10.1038/nri2413
Qiu H, Huang F, Gong J, Xiao H, Sun BL, Yang RG (2015) TRIM22 can activate the noncanonical NF-kappaB pathway by affecting IKKalpha. J Receptor Signal Transduct Res 35(4):289–294. https://doi.org/10.3109/10799893.2014.977450
Qiu H, Huang F, Xiao H, Sun B, Yang R (2013) TRIM22 inhibits the TRAF6-stimulated NF-kappaB pathway by targeting TAB2 for degradation. Virol Sinica 28(4):209–215. https://doi.org/10.1007/s12250-013-3343-4
Radak D, Katsiki N, Resanovic I, Jovanovic A, Sudar-Milovanovic E, Zafirovic S, Mousad SA, Isenovic ER (2017) Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol 15(2):115–122. https://doi.org/10.2174/1570161115666161104095522
Ribeiro PW, Cola PC, Gatto AR, da Silva RG, Luvizutto GJ, Braga GP, Schelp AO, de Arruda Henry MA, Bazan R (2015) Relationship between dysphagia, national institutes of health stroke scale score, and predictors of pneumonia after ischemic stroke. J Stroke Cerebrovasc Dis 24(9):2088–2094. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.05.009
Sagoo P, Chan G, Larkin DF, George AJ (2004) Inflammatory cytokines induce apoptosis of corneal endothelium through nitric oxide. Invest Ophthalmol Vis Sci 45(11):3964–3973. https://doi.org/10.1167/iovs.04-0439
Sheth KN, Smith EE, Grau-Sepulveda MV, Kleindorfer D, Fonarow GC, Schwamm LH (2015) Drip and ship thrombolytic therapy for acute ischemic stroke: use, temporal trends, and outcomes. Stroke 46(3):732–739. https://doi.org/10.1161/strokeaha.114.007506
Sun Y, Ho GH, Koong HN, Sivaramakrishnan G, Ang WT, Koh QM, Lin VC (2013) Down-regulation of tripartite-motif containing 22 expression in breast cancer is associated with a lack of p53-mediated induction. Biochem Biophys Res Commun 441(3):600–606. https://doi.org/10.1016/j.bbrc.2013.10.110
Turrini F, Marelli S, Kajaste-Rudnitski A, Lusic M, Van Lint C, Das AT, Harwig A, Berkhout B, Vicenzi E (2015) HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter. Retrovirology 12:104. https://doi.org/10.1186/s12977-015-0230-0
Venuto S, Merla G (2019) E3 ubiquitin ligase TRIM proteins, cell cycle and mitosis. Cells. https://doi.org/10.3390/cells8050510
Watanabe M, Hatakeyama S (2017) TRIM proteins and diseases. J Biochem 161(2):135–144. https://doi.org/10.1093/jb/mvw087
Yang C, Zhao X, Sun D, Yang L, Chong C, Pan Y, Chi X, Gao Y, Wang M, Shi X, Sun H, Lv J, Gao Y, Zhong J, Niu J, Sun B (2016) Interferon alpha (IFNalpha)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A. Cell Mol Immunol 13(1):94–102. https://doi.org/10.1038/cmi.2014.131
Yu S, Gao B, Duan Z, Xu W, Xiong S (2011) Identification of tripartite motif-containing 22 (TRIM22) as a novel NF-kappaB activator. Biochem Biophys Res Commun 410(2):247–251. https://doi.org/10.1016/j.bbrc.2011.05.124
Zhan W, Han T, Zhang C, Xie C, Gan M, Deng K, Fu M, Wang JB (2015) TRIM59 promotes the proliferation and migration of non-small cell lung cancer cells by Upregulating cell cycle related proteins. PLoS ONE 10(11):e0142596. https://doi.org/10.1371/journal.pone.0142596
Acknowledgements
This work was supported by High level cultivation fund of Henan University of Science and Technology (2015GJB021) and Project fund of science and technology department of henan province (164102310412).
Funding
This work was supported by High level cultivation fund of Henan University of Science and Technology (2015GJB021) and Project fund of science and technology department of henan province (164102310412).
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. CK, GZ and YC performed cellular and molecular experiments in the research. Material preparation, data collection and analysis were performed by CK, YC and YW. The first draft of the manuscript was written by CK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval
Animal experiments in this study were approved by the Institutional Animal Care and Use Committee of First Affiliated Hospital of Henan University of Science and Technology.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kang, C., Lu, Z., Zhu, G. et al. Knockdown of TRIM22 Relieves Oxygen–Glucose Deprivation/Reoxygenation-Induced Apoptosis and Inflammation Through Inhibition of NF-κB/NLRP3 Axis. Cell Mol Neurobiol 41, 341–351 (2021). https://doi.org/10.1007/s10571-020-00855-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-020-00855-w