Receptor-interacting protein kinase 3-mediated programmed cell necrosis in rats subjected to focal cerebral ischemia-reperfusion injury

Dong,Yanru; Bao,Cuifen; Yu,Jingwei; Liu,Xia

doi:10.3892/mmr.2016.5311

Receptor-interacting protein kinase 3-mediated programmed cell necrosis in rats subjected to focal cerebral ischemia-reperfusion injury

Authors:
- Yanru Dong
- Cuifen Bao
- Jingwei Yu
- Xia Liu
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Affiliations: Department of Histology and Embryology, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China, Key Laboratory of Molecular Cell Biology and New Drug Development, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: May 19, 2016 https://doi.org/10.3892/mmr.2016.5311
Pages: 728-736
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the current study, the activation of tumor necrosis factor-α receptor 1 (TNFR1) and receptor-interacting protein kinase 3 (RIP3) were investigated following cerebral ischemia-reperfusion injury (CIRI). Healthy SD rats were randomly divided into 3 groups: Sham operation group, model group and inhibitor group. The model group and inhibitor group were further divided into 4 subgroups of 6, 12, 24 and 72 h following CIRI. Using right middle cerebral artery embolization, the CIRI model was generated. To confirm that the CIRI model was established, neurological scores, TTC staining and brain water content measurements were conducted. Immunohistochemistry and western blotting were conducted to investigate the expression of TNFR1 and RIP3 in the cerebral cortex. It was observed that nerve cell necrosis occurred following 6 h of CIRI. The appearance of necrotic cells was gradually increased with increasing CIRI duration. TNFR1 and RIP3 were positively expressed following 6 h of CIRI. With increasing durations of CIRI, the protein expression levels of TNFR1 and RIP3 were significantly increased. Pre‑administration with Z-VAD-FMK (zVAD) significantly increased the protein level of RIP3, however, had no effect on the levels of TNFR1, and was accompanied by a reduction in necrosis. In conclusion, RIP3‑mediated cell necrosis was enhanced by caspase blockade zVAD and the function of zVAD was independent of TNFR1 signaling following IR.

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1	Cerqueira NF, Hussni CA and Yoshida WB: Pathophysiology of mesenteric ischemia/reperfusion: A review. Acta Cir Bras. 20:336–343. 2005. View Article : Google Scholar : PubMed/NCBI
2	Takahashi H, Xia P, Cui J, Talantova M, Bodhinathan K, Li W, Holland EA, Tong G, Piña Crespo J, Zhang D, et al: Pharmacologically targeted NMDA receptor antagonism by NitroMemantine for cerebrovascular disease. Sci Rep. 5:147812015. View Article : Google Scholar : PubMed/NCBI
3	Granger DN and Kvietys PR: Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol. 6:524–551. 2015. View Article : Google Scholar : PubMed/NCBI
4	Xu M, Chen X, Gu Y, Peng T, Yang D, Chang RC, So KF, Liu K and Shen J: Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemia-reperfusion injury. J Ethnopharmacol. 150:116–124. 2013. View Article : Google Scholar : PubMed/NCBI
5	Wang J, Wang P, Li S, Wang S, Li Y, Liang N and Wang M: Mdivi-1 prevents apoptosis induced by ischemia-reperfusion injury in primary hippocampal cells via inhibition of reactive oxygen species-activated mitochondrial pathway. J Stroke Cerebrovasc Dis. 23:1491–1499. 2014. View Article : Google Scholar : PubMed/NCBI
6	Van Herreweghe F, Festjens N, Declercq W and Vandenabeele P: Tumor necrosis factor-mediated cell death: To break or to burst, that's the question. Cell Mol Life Sci. 67:1567–1579. 2010. View Article : Google Scholar : PubMed/NCBI
7	Xanthoulea S, Pasparakis M, Kousteni S, Brakebusch C, Wallach D, Bauer J, Lassmann H and Kollias G: Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases. J Exp Med. 200:367–376. 2004. View Article : Google Scholar : PubMed/NCBI
8	He S, Wang L, Miao L, Wang T, Du F, Zhao L and Wang X: Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-α. Cell. 137:1100–1111. 2009. View Article : Google Scholar : PubMed/NCBI
9	Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A, et al: The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 150:339–350. 2012. View Article : Google Scholar : PubMed/NCBI
10	Wu W, Liu P and Li J: Necroptosis: An emerging form of programmed cell death. Crit Rev Oncol Hematol. 82:249–258. 2012. View Article : Google Scholar
11	Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M and Chan FK: Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 137:1112–1123. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kaiser WJ, Upton JW, Long AB, Livingston-Rosanoff D, Daley-Bauer LP, Hakem R, Caspary T and Mocarski ES: RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 471:368–372. 2011. View Article : Google Scholar : PubMed/NCBI
13	Vandenabeele P, Declercq W, Van Herreweghe F and Vanden Berghe T: The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal. 3:re42010. View Article : Google Scholar : PubMed/NCBI
14	Moriwaki K and Chan FK: RIP3: A molecular switch for necrosis and inflammation. Genes Dev. 27:1640–1649. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhang DW, Zheng M, Zhao J, Li YY, Huang Z, Li Z and Han J: Multiple death pathways in TNF-treated fibroblasts: RIP3- and RIP1-dependent and independent routes. Cell Res. 21:368–371. 2011. View Article : Google Scholar : PubMed/NCBI
16	Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ and Han J: RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 325:332–336. 2009. View Article : Google Scholar : PubMed/NCBI
17	National Research Council (USA) Institute for Laboratory Animal Research: Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press (USA); Washington, DC: 1996
18	Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI
19	Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z and Lindvall O: Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke. 38:3032–3039. 2007. View Article : Google Scholar : PubMed/NCBI
20	Swanson RA, Morton MT, Tsao-Wu G, Savalos RA, Davidson C and Sharp FR: A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab. 10:290–293. 1990. View Article : Google Scholar : PubMed/NCBI
21	Kim SJ and Li J: Caspase blockade induces RIP3-mediated programmed necrosis in Toll-like receptor-activated microglia. Cell Death Dis. 4:e7162013. View Article : Google Scholar : PubMed/NCBI
22	Durai Pandian J, Padma V, Vijaya P, Sylaja PN and Murthy JM: Stroke and thrombolysis in developing countries. Int J Stroke. 2:17–26. 2007. View Article : Google Scholar
23	Xu D, Du W, Zhao L, Davey AK and Wang J: The neuroprotective effects of isosteviol against focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats. Planta Med. 74:816–821. 2008. View Article : Google Scholar : PubMed/NCBI
24	Budohoski KP, Guilfoyle M, Helmy A, Huuskonen T, Czosnyka M, Kirollos R, Menon DK, Pickard JD and Kirkpatrick PJ: The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 85:1343–1353. 2014. View Article : Google Scholar : PubMed/NCBI
25	Xu H, Zhang Y, Sun H, Chen S and Wang F: Effects of acupuncture at GV20 and ST36 on the expression of matrix metalloproteinase 2, aquaporin 4, and aquaporin 9 in rats subjected to cerebral ischemia/reperfusion injury. PLoS One. 9:e974882014. View Article : Google Scholar : PubMed/NCBI
26	Chen HJ, Shen YC, Shiao YJ, Liou KT, Hsu WH, Hsieh PH, Lee CY, Chen YR and Lin YL: Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice. PLoS One. 10:e01408232015. View Article : Google Scholar : PubMed/NCBI
27	Li W, Tan C, Liu Y, Liu X, Wang X, Gui Y, Qin L, Deng F, Yu Z, Hu C and Chen L: Resveratrol ameliorates oxidative stress and inhibits aquaporin 4 expression following rat cerebral ischemia-reperfusion injury. Mol Med Rep. 12:7756–7762. 2015.PubMed/NCBI
28	Saini MK, Sanyal SN and Vaiphei K: Piroxicam and C-phycocyanin mediated apoptosis in 1,2-dimethylhydrazine dihydrochloride induced colon carcinogenesis: Exploring the mitochondrial pathway. Nutr Cancer. 64:409–418. 2012. View Article : Google Scholar : PubMed/NCBI
29	Günther C, Martini E, Wittkopf N, Amann K, Weigmann B, Neumann H, Waldner MJ, Hedrick SM, Tenzer S, Neurath MF and Becker C: Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature. 477:335–339. 2011. View Article : Google Scholar
30	Bamias G, Jia LG and Cominelli F: The tumor necrosis factor-like cytokine 1A/death receptor 3 cytokine system in intestinal inflammation. Curr Opin Gastroenterol. 29:597–602. 2013. View Article : Google Scholar : PubMed/NCBI
31	Ma J, Endres M and Moskowitz MA: Synergistic effects of caspase inhibitors and MK-801 in brain injury after transient focal cerebral ischaemia in mice. Br J Pharmacol. 124:756–762. 1998. View Article : Google Scholar : PubMed/NCBI
32	Madsen PM, Clausen BH, Degn M, Thyssen S, Kristensen LK, Svensson M, Ditzel N, Finsen B, Deierborg T, Brambilla R and Lambertsen KL: Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia. J Cereb Blood Flow Metab. Oct 19–2015.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
33	Xu Y, Wang J, Song X, Wei R, He F, Peng G and Luo B: Protective mechanisms of CA074-me (other than cathepsin-B inhibition) against programmed necrosis induced by global cerebral ischemia/reperfusion injury in rats. Brain Res Bull. 120:97–105. 2016. View Article : Google Scholar
34	Moulin M, Anderton H, Voss AK, Thomas T, Wong WW, Bankovacki A, Feltham R, Chau D, Cook WD, Silke J and Vaux DL: IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J. 31:1679–1691. 2012. View Article : Google Scholar : PubMed/NCBI
35	Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA and Yuan J: Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 1:112–119. 2005. View Article : Google Scholar
36	Yeh WC, Itie A, Elia AJ, Ng M, Shu HB, Wakeham A, Mirtsos C, Suzuki N, Bonnard M, Goeddel DV and Mak TW: Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity. 12:633–642. 2000. View Article : Google Scholar : PubMed/NCBI
37	Boise LH, Minn AJ, Noel PJ, June CH, Accavitti MA, Lindsten T and Thompson CB: CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL. Immunity. 3:87–98. 1995. View Article : Google Scholar : PubMed/NCBI
38	Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P, Pop C, Hakem R, Salvesen GS and Green DR: Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 471:363–367. 2011. View Article : Google Scholar : PubMed/NCBI