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Selenium Deficiency via the ROS/NLRP3/IL-1β Signaling Pathway Leads to Pyroptosis Injury in Pig Spleen

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Abstract

The aim of the present study was to investigate the effect of selenium (Se) deficiency on the relationship between the pyroptosis and MAPK signaling pathway in spleen injury. A total of 10 two-month-old Sus scrofa domesticus specimens were allocated to two groups. The control group was fed a basal diet (0.15-mg/kg Se), and the experimental group was fed a 0.03-mg/kg Se-deficient diet for 2 months. The pig-spleen histopathological changes were observed with hematoxylin–eosin staining. Frozen sections were prepared to detect the content of ROS in pig-spleen cells. The oxidation stress related indexes were determined using a spectrophotometer. The levels of pyroptosis- and MAPK signaling pathway-related factors were detected via quantitative real-time polymerase chain reaction (qPCR) and western blotting (WB). The results of sections showed that the lymphocytes decreased in number, the spacing of cells widened, and some cells were necrotic in the spleen tissue of pigs fed a low-selenium diet. The content of ROS, malondialdehyde, nitric oxide, H2O2, and catalase activity in the low-selenium group was significantly higher than that in the control group, and SOD activity was decreased. The protein-ratio-levels of p-Nrf2 to Nrf2 were decreased. The expression levels of nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3), IL-1β, IL-18, ASC, gasdermin D, and caspase-1, the protein-ratio-levels of p-AKT serine/threonine kinase (p-AKT) to AKT, p-extracellular regulated protein kinases (ERK) to ERK, p-P38 MAPK to p-P38, and p–c-Jun N-terminal kinase (p-JNK) to JNK were significantly increased in the Se-deficient group compared with the control group. These results suggested that Se deficiency can induce oxidant stress, which increases pyroptosis- and inflammation-related factors of pig-spleen injury.

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References

  1. Gać P, Czerwińska K, Macek P, Jaremków A, Mazur G, Pawlas K, Poręba R (2021) The importance of selenium and zinc deficiency in cardiovascular disorders. Environ Toxicol Pharmacol 82:103553. https://doi.org/10.1016/j.etap.2020.103553

    Article  CAS  PubMed  Google Scholar 

  2. Wang N, Tan HY, Li S, Xu Y, Guo W, Feng Y (2017) Supplementation of micronutrient selenium in metabolic diseases: its role as an antioxidant. Oxid Med Cell Longev 2017:7478523. https://doi.org/10.1155/2017/7478523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rayman MP (2012) Selenium and human health. Lancet 379(9822):1256–1268. https://doi.org/10.1016/s0140-6736(11)61452-9

    Article  CAS  Google Scholar 

  4. Holben DH, Smith AM (1999) The diverse role of selenium within selenoproteins: a review. J Am Diet Assoc 99(7):836–843. https://doi.org/10.1016/s0002-8223(99)00198-4

    Article  CAS  PubMed  Google Scholar 

  5. Rosen BP, Liu Z (2009) Transport pathways for arsenic and selenium: a minireview. Environ Int 35(3):512–515. https://doi.org/10.1016/j.envint.2008.07.023

    Article  CAS  PubMed  Google Scholar 

  6. Papp LV, Lu J, Holmgren A, Khanna KK (2007) From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 9(7):775–806. https://doi.org/10.1089/ars.2007.1528

    Article  CAS  PubMed  Google Scholar 

  7. Ding D, Mou D, Zhao L, Jiang X, Che L, Fang Z, Xu S et al (2021) Maternal organic selenium supplementation alleviates LPS induced inflammation, autophagy and ER stress in the thymus and spleen of offspring piglets by improving the expression of selenoproteins. Food Funct 12(22):11214–11228. https://doi.org/10.1039/d1fo01653a

    Article  CAS  PubMed  Google Scholar 

  8. Zhang R, Qi J, Zhou M, Pan T, Zhang Z, Yao Y, Han H, Han Y (2021) Upregulation of Nrf2 attenuates oxidative stress-induced, complement activation-associated endothelial injury and apoptosis in transplant-associated thrombotic microangiopathy. Transplant Cell Ther 27(9):758.e751-758.e758. https://doi.org/10.1016/j.jtct.2021.06.017

    Article  CAS  Google Scholar 

  9. Thiruvengadam M, Venkidasamy B, Subramanian U, Samynathan R, Ali Shariati M, Rebezov M, Girish S, Thangavel S, et al (2021) Bioactive compounds in oxidative stress-mediated diseases: targeting the NRF2/ARE signaling pathway and epigenetic regulation. Antioxidants (Basel) 10(12). https://doi.org/10.3390/antiox10121859

  10. Su L, Zhang J, Gomez H, Kellum JA, Peng Z (2022) Mitochondria ROS and mitophagy in acute kidney injury. Autophagy 1–14. https://doi.org/10.1080/15548627.2022.2084862

  11. Xian H, Watari K, Sanchez-Lopez E, Offenberger J, Onyuru J, Sampath H, Ying W et al (2022) Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling. Immunity 55(8):1370-1385.e1378. https://doi.org/10.1016/j.immuni.2022.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wei P, Yang F, Zheng Q, Tang W, Li J (2019) The potential role of the NLRP3 inflammasome activation as a link between mitochondria ROS generation and neuroinflammation in postoperative cognitive dysfunction. Front Cell Neurosci 13:73. https://doi.org/10.3389/fncel.2019.00073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. He Y, Hara H, Núñez G (2016) Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 41(12):1012–1021. https://doi.org/10.1016/j.tibs.2016.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10(2):417–426. https://doi.org/10.1016/s1097-2765(02)00599-3

    Article  CAS  PubMed  Google Scholar 

  15. Lei Q, Yi T, Chen C (2018) NF-κB-Gasdermin D (GSDMD) axis couples oxidative stress and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis following myocardial infarction. Med Sci Monit 24:6044–6052. https://doi.org/10.12659/msm.908529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y et al (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526(7575):660–665. https://doi.org/10.1038/nature15514

    Article  CAS  PubMed  Google Scholar 

  17. He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J (2015) Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res 25(12):1285–1298. https://doi.org/10.1038/cr.2015.139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, Junqueira C et al (2020) Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature 579(7799):415–420. https://doi.org/10.1038/s41586-020-2071-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, Wang Y et al (2020) Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science 368(6494). https://doi.org/10.1126/science.aaz7548

  20. Wang Y, Gao W, Shi X, Ding J, Liu W, He H, Wang K, Shao F (2017) Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547(7661):99–103. https://doi.org/10.1038/nature22393

    Article  CAS  PubMed  Google Scholar 

  21. Wang Q, Wang Y, Ding J, Wang C, Zhou X, Gao W, Huang H et al (2020) A bioorthogonal system reveals antitumour immune function of pyroptosis. Nature 579(7799):421–426. https://doi.org/10.1038/s41586-020-2079-1

    Article  CAS  PubMed  Google Scholar 

  22. Li S, Sun W, Zhang K, Zhu J, Jia X, Guo X, Zhao Q et al (2021) Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis. J Anim Sci Biotechnol 12(1):65. https://doi.org/10.1186/s40104-021-00587-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li S, Sun Y, Song M, Song Y, Fang Y, Zhang Q, Li X et al (2021) NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression. JCI Insight 6(23):e146852. https://doi.org/10.1172/jci.insight.146852

    Article  PubMed  PubMed Central  Google Scholar 

  24. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270(5240):1326–1331. https://doi.org/10.1126/science.270.5240.1326

    Article  CAS  PubMed  Google Scholar 

  25. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286(5443):1358–1362. https://doi.org/10.1126/science.286.5443.1358

    Article  CAS  PubMed  Google Scholar 

  26. Zhang Z, Zhang H, Li D, Zhou X, Qin Q, Zhang Q (2021) Caspase-3-mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway. J Cell Mol Med 25(17):8159–8168. https://doi.org/10.1111/jcmm.16574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Matsumoto T, Turesson I, Book M, Gerwins P, Claesson-Welsh L (2002) p38 MAP kinase negatively regulates endothelial cell survival, proliferation, and differentiation in FGF-2-stimulated angiogenesis. J Cell Biol 156(1):149–160. https://doi.org/10.1083/jcb.200103096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Stefani C, Miricescu D, Stanescu S II, Nica RI, Greabu M, Totan AR, Jinga M (2021) Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: where are we now? Int J Mol Sci 22:10260. https://doi.org/10.3390/ijms221910260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ulasov AV, Rosenkranz AA, Georgiev GP, Sobolev AS (2022) Nrf2/Keap1/ARE signaling: Towards specific regulation. Life Sci 291:120111. https://doi.org/10.1016/j.lfs.2021.120111

    Article  CAS  PubMed  Google Scholar 

  30. Shen C, Wang J, Feng M, Peng J, Du X, Chu H, Chen X (2021) The mitochondrial-derived peptide MOTS-c attenuates oxidative stress injury and the inflammatory response of H9c2 cells through the Nrf2/ARE and NF-κB pathways. Cardiovasc Eng Technol. https://doi.org/10.1007/s13239-021-00589-w

    Article  PubMed  Google Scholar 

  31. Ran Y, Su W (2021) Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition. Oxid Med Cell Longev 2021:1552127. https://doi.org/10.1155/2021/1552127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zheng Y, Zhang B, Guan H, Jiao X, Yang J, Cai J, Liu Q et al (2021) Selenium deficiency causes apoptosis through endoplasmic reticulum stress in swine small intestine. BioFactors 47:788–800. https://doi.org/10.1002/biof.1762

    Article  CAS  PubMed  Google Scholar 

  33. Zhang C, Wang X, Nie G, Wei Z, Pi S, Wang C, Yang F et al (2021) In vivo assessment of molybdenum and cadmium co-induce nephrotoxicity via NLRP3/Caspase-1-mediated pyroptosis in ducks. J Inorg Biochem 224:111584. https://doi.org/10.1016/j.jinorgbio.2021.111584

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Natural Science Foundation of Henan Province (202300410008) and the Natural Science Foundation of China (32102744).

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Authors and Affiliations

  1. Henan Provincial Key Laboratory of Subcritical High-Efficiency Extraction, Anyang Institute of Technology, Huanghe Rd. 20, Anyang, 455000, Henan, China

    Lichao Song, Zhihui Jiang, Xingwang Zhang, Yuwei Song, Yueteng Xing & Guodong Wang

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  1. Lichao Song
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  2. Zhihui Jiang
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  4. Yuwei Song
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Lichao Song, Zhihui Jiang, Xingwang Zhang, and Yuwei Song. The first draft of the manuscript was written by Lichao Song, Zhihui Jiang, and Guodong Wang, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhihui Jiang.

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The institution of Animal Protection and Utilization Committee at Anyang Institute of Technology approved this experiment.

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Song, L., Jiang, Z., Zhang, X. et al. Selenium Deficiency via the ROS/NLRP3/IL-1β Signaling Pathway Leads to Pyroptosis Injury in Pig Spleen. Biol Trace Elem Res 201, 5192–5200 (2023). https://doi.org/10.1007/s12011-023-03595-2

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