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01-06-2021 | Sufentanil | Original Article

Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression

Authors: Ling Zhou, Xinlu Yang, Shuhua Shu, Sheng Wang, Fenglin Guo, Ying Yin, Weide Zhou, Han Han, Xiaoqing Chai

Published in: Inflammation | Issue 3/2021

Abstract

Liver ischemia-reperfusion (I/R) injury is a pathological process that often occurs during liver and trauma surgery. This study aimed to investigate the protective effect and potential mechanisms of sufentanil on hepatic I/R injury. I/R rat model and hypoxic/reoxygenation (H/R)-induced buffalo rat liver (BRL)-3A cell model were established. Following pretreatment with sufentanil, the enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rat serum and the changes of hepatic histopathology were evaluated to track the extent of liver injury. The levels of inflammatory factors were determined with ELISA kits and RT-qPCR. The infiltration of macrophages was assessed after detecting monocyte chemoattractant protein 1 (MCP-1) and F4/80 expression. Additionally, apoptosis was measured by means of TUNEL staining, and gene expression related to apoptosis was examined using RT-qPCR and western blotting. Then, TP53BP2 was overexpressed in BRL-3A cells exposed to H/R condition to evaluate whether sufentanil defended the liver against injury by regulating TP53BP2 expression. Moreover, the potential binding site of ATF4 on the TP53BP2 promoter was analyzed using JASPAR databases and verified by chromosomal immunoprecipitation (ChIP) assay. Furthermore, TP53BP2 expression and endoplasmic reticulum stress (ERS)-related protein levels were determined after ATF4 was overexpressed in sufentanil-treated BRL-3A cells. Results revealed that sufentanil significantly improved hepatic I/R injury, decreased the levels of inflammatory factors, and alleviated hepatocyte apoptosis. Notably, upregulated TP53BP2 expression was observed in hepatic tissues, and TP53BP2 overexpression markedly reversed the protective effects of sufentanil on the inflammation and apoptosis in H/R-stimulated BRL-3A cells. Additionally, ATF4 was confirmed to combine with the TP53BP2 promoter. ATF4 upregulation attenuated the inhibitory effects of sufentanil on the expression of TP53BP2 and ERS-associated proteins. These findings demonstrated that sufentanil protects the liver from inflammation and apoptosis injury induced by I/R by inhibiting ATF4 expression and further suppressing TP53BP2 expression, suggesting a promising therapeutic candidate for the treatment of liver I/R injury.

Ajamieh, H., G.C. Farrell, R.S. McCuskey, J. Yu, E. Chu, H.J. Wong, W. Lam, and N.C. Teoh. 2015. Acute atorvastatin is hepatoprotective against ischaemia-reperfusion injury in mice by modulating eNOS and microparticle formation. Liver International 35 (9): 2174–2186. https://doi.org/10.1111/liv.12827.CrossRefPubMed

Bergamaschi, D., Y. Samuels, B. Jin, S. Duraisingham, T. Crook, and X. Lu. 2004. ASPP1 and ASPP2: common activators of p53 family members. Molecular and Cellular Biology 24 (3): 1341–1350. https://doi.org/10.1128/mcb.24.3.1341-1350.2004.CrossRefPubMedPubMedCentral

Bergamaschi, D., Y. Samuels, A. Sullivan, M. Zvelebil, H. Breyssens, A. Bisso, G. Del Sal, et al. 2006. iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nature Genetics 38 (10): 1133–1141. https://doi.org/10.1038/ng1879.CrossRefPubMed

Brenner, C., L. Galluzzi, O. Kepp, and G. Kroemer. 2013. Decoding cell death signals in liver inflammation. Journal of Hepatology 59 (3): 583–594. https://doi.org/10.1016/j.jhep.2013.03.033.CrossRefPubMed

Cairo, G., L. Bardella, L. Schiaffonati, and A. Bernelli-Zazzera. 1985. Synthesis of heat shock proteins in rat liver after ischemia and hyperthermia. Hepatology 5 (3): 357–361. https://doi.org/10.1002/hep.1840050303.CrossRefPubMed

Chi, X.B., Y. Jiang, Y.B. Chen, F. Yang, Q.C. Cai, F. Pan, L.Z. Lv, and X.J. Zhang. 2019. Suppression of microRNA-27a protects against liver ischemia/reperfusion injury by targeting PPAR gamma and inhibiting endoplasmic reticulum stress. Molecular Medicine Reports 20 (5): 4003–4012. https://doi.org/10.3892/mmr.2019.10645.CrossRefPubMed

Guo, Q.Y., H.X. Li, J.L. Liu, L. Xu, L. Yang, Z.M. Sun, and B. Zhou. 2017. Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHOP signaling in amurine model of neutrophilic asthma. Journal of Asthma 54 (2): 125–133. https://doi.org/10.1080/02770903.2016.1205085.CrossRef

Hu, Q., Q. Wang, C.G. Han, and Y. Yang. 2020. Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression. Molecular Medicine Reports 22 (5): 4298–4306. https://doi.org/10.3892/mmr.2020.11526.CrossRefPubMedPubMedCentral

Jaeschke, H., and B.L. Woolbright. 2012. Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transplantation Reviews (Orlando, Fla.) 26 (2): 103–114. https://doi.org/10.1016/j.trre.2011.10.006.CrossRef

10.

Jiang, P., Z.W. Zou, R.S. Tu, S. Wang, and H.F. Yun. 2020. Sufentanil attenuates inflammation and oxidative stress in myocardial ischemia reperfusion injury via upregulating Sestrin 2 expression and activating AMPK signalling pathway. Biotechnology & Biotechnological Equipment 34 (1): 203–210. https://doi.org/10.1080/13102818.2020.1728197.CrossRef

11.

Kalogeris, T., C.P. Baines, M. Krenz, and R.J. Korthuis. 2012. Cell biology of ischemia/reperfusion injury. International Review of Cell and Molecular Biology 298: 229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7.CrossRefPubMedPubMedCentral

12.

Kang, J.W., and S.M. Lee. 2016. Resolvin D1 protects the liver from ischemia/reperfusion injury by enhancing M2 macrophage polarization and efferocytosis. Biochimica et Biophysica Acta 1861 (9 Pt A): 1025–1035. https://doi.org/10.1016/j.bbalip.2016.06.002.CrossRefPubMed

13.

Karaman, A., E. Fadillioglu, E. Turkmen, E. Tas, and Z. Yilmaz. 2006. Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver. Pediatric Surgery International 22 (5): 428–434. https://doi.org/10.1007/s00383-006-1668-x.CrossRefPubMed

14.

Kou, X.N., J. Zhu, X.K. Xie, M.X. Hao, and Y.R. Zhao. 2020. The protective effect of glycyrrhizin on hepatic ischemia-reperfusion injury in rats and possible related signal pathway. Iranian Journal of Basic Medical Sciences 23 (9): 1232–1238. https://doi.org/10.22038/ijbms.2020.44101.10334.CrossRefPubMedPubMedCentral

15.

Li, H., G. Bai, Y.S. Ge, Q.Z. Zhang, X.D. Kong, W.J. Meng, and H.B. Wang. 2018. Hydrogen-rich saline protects against small-scale liver ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress. Life Sciences 194: 7–14. https://doi.org/10.1016/j.lfs.2017.12.022.CrossRefPubMed

16.

Li, L.S., Y. Sun, N. Zhang, X.M. Qiu, L. Wang, and Q.Y. Luo. 2019. By regulating miR-182-5p/BCL10/CYCS, sufentanil reduces the apoptosis of umbilical cord mesenchymal stem cells caused by ropivacaine. Bioscience Trends 13 (1): 49–57. https://doi.org/10.5582/bst.2018.01291.CrossRefPubMed

17.

Lian, Y.H., J. Fang, H.D. Zhou, H.F. Jiang, and K.J. Xie. 2019. Sufentanil preconditioning protects against hepatic ischemia-reperfusion injury by suppressing inflammation. Medical Science Monitor 25: 2265–2273. https://doi.org/10.12659/MSM.913145.CrossRefPubMedPubMedCentral

18.

Liu, K., Y. Shi, X. Guo, S. Wang, Y. Ouyang, M. Hao, D. Liu, L. Qiao, N. Li, J. Zheng, and D. Chen. 2014. CHOP mediates ASPP2-induced autophagic apoptosis in hepatoma cells by releasing Beclin-1 from Bcl-2 and inducing nuclear translocation of Bcl-2. Cell Death & Disease 5: e1323. https://doi.org/10.1038/cddis.2014.276.CrossRef

19.

Liu, Y. 2020. Hydrogen peroxide induces nucleus pulposus cell apoptosis by ATF4/CHOP signaling pathway. Experimental and Therapeutic Medicine 20 (4): 3244–3252. https://doi.org/10.3892/etm.2020.9052.CrossRefPubMedPubMedCentral

20.

Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25 (4): 402–408. https://doi.org/10.1006/meth.2001.1262.CrossRef

21.

Ma, X.X., F. Luo, and N. Lan. 2019. Effects of dexmedetomidine combined with sufentanil on P2X7 receptor expression in peripheral blood mononuclear cells in patients with burn pain. Acta Microscópica 28 (4): 785–790.

22.

Mahmoud, A.R., F.E.M. Ali, T.H. Abd-Elhamid, and E.H.M. Hassanein. 2019. Coenzyme Q10 protects hepatocytes from ischemia reperfusion-induced apoptosis and oxidative stress via regulation of Bax/Bcl-2/PUMA and Nrf-2/FOXO-3/Sirt-1 signaling pathways. Tissue & Cell 60: 1–13. https://doi.org/10.1016/j.tice.2019.07.007.CrossRef

23.

Mitupatum, T., K. Aree, S. Kittisenachai, S. Roytrakul, S. Puthong, S. Kangsadalampai, and P. Rojpibulstit. 2016. mRNA expression of Bax, Bcl-2, p53, cathepsin B, caspase-3 and caspase-9 in the HepG2 cell line following induction by a novel monoclonal Ab Hep88 mAb: cross-talk for paraptosis and apoptosis. Asian Pacific Journal of Cancer Prevention 17 (2): 703–712. https://doi.org/10.7314/apjcp.2016.17.2.703.CrossRefPubMed

24.

Nasrallah, H., I. Aissa, C. Slim, M.A. Boujbiha, M.A. Zaouali, M. Bejaoui, V. Wilke, H. Ben Jannet, H. Mosbah, and H. Ben Abdennebi. 2020. Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney. Life Sciences 255: 8. https://doi.org/10.1016/j.lfs.2020.117833.CrossRef

25.

Nastos, C., K. Kalimeris, N. Papoutsidakis, M.K. Tasoulis, P.M. Lykoudis, K. Theodoraki, D. Nastou, V. Smyrniotis, and N. Arkadopoulos. 2014. Global consequences of liver ischemia/reperfusion injury. Oxidative Medicine and Cellular Longevity 2014: 906965–906913. https://doi.org/10.1155/2014/906965.CrossRefPubMedPubMedCentral

26.

Rao, J.H., J.J. Qin, X.F. Qian, L. Lu, P. Wang, Z.S. Wu, Y. Zhai, F. Zhang, G.Q. Li, and X.H. Wang. 2013. Lipopolysaccharide preconditioning protects hepatocytes from ischemia/reperfusion injury (IRI) through inhibiting ATF4-CHOP pathway in mice. PLoS One 8 (6): 13. https://doi.org/10.1371/journal.pone.0065568.CrossRef

27.

Samuels-Lev, Y., D.J. O'Connor, D. Bergamaschi, G. Trigiante, J.K. Hsieh, S. Zhong, I. Campargue, L. Naumovski, T. Crook, and X. Lu. 2001. ASPP proteins specifically stimulate the apoptotic function of p53. Molecular Cell 8 (4): 781–794. https://doi.org/10.1016/s1097-2765(01)00367-7.CrossRefPubMed

28.

Shaker, M.E., B.N. Trawick, and W.Z. Mehal. 2016. The novel TLR9 antagonist COV08-0064 protects from ischemia/reperfusion injury in non-steatotic and steatotic mice livers. Biochemical Pharmacology 112: 90–101. https://doi.org/10.1016/j.bcp.2016.05.003.CrossRefPubMed

29.

Sun, P., P. Zhang, P.X. Wang, L.H. Zhu, Y. Du, S. Tian, X. Zhu, and H. Li. 2015. Mindin deficiency protects the liver against ischemia/reperfusion injury. Journal of Hepatology 63 (5): 1198–1211. https://doi.org/10.1016/j.jhep.2015.06.033.CrossRefPubMed

30.

Theruvath, T.P., Z. Zhong, R.T. Currin, V.K. Ramshesh, and J.J. Lemasters. 2006. Endothelial nitric oxide synthase protects transplanted mouse livers against storage/reperfusion injury: role of vasodilatory and innate immunity pathways. Transplantation Proceedings 38 (10): 3351–3357. https://doi.org/10.1016/j.transproceed.2006.10.171.CrossRefPubMedPubMedCentral

31.

Vaughn, S.E. 2012. Review of the third edition of the guide for the care and use of agricultural animals in research and teaching. Journal of the American Association for Laboratory Animal Science 51 (3): 298–300.PubMedPubMedCentral

32.

Wei, Q.Q., X.F. Hu, and D. Zhang. 2020. Propofol attenuates hepatic ischemia-reperfusion injury in rats by reducing inflammation, oxidative stress and apoptosis. Latin American Journal of Pharmacy 39 (5): 1040–1046.

33.

Wu, Q.L., T. Shen, H. Ma, and J.K. Wang. 2012. Sufentanil postconditioning protects the myocardium from ischemia-reperfusion via PI3K/Akt-GSK-3 beta pathway. Journal of Surgical Research 178 (2): 563–570. https://doi.org/10.1016/j.jss.2012.05.081.CrossRef

34.

Xiao, Q., Q. Ye, W. Wang, J. Xiao, B. Fu, Z. Xia, X. Zhang, Z. Liu, and X. Zeng. 2017. Mild hypothermia pretreatment protects against liver ischemia reperfusion injury via the PI3K/AKT/FOXO3a pathway. Molecular Medicine Reports 16 (5): 7520–7526. https://doi.org/10.3892/mmr.2017.7501.CrossRefPubMedPubMedCentral

35.

Xiao, Y., S.H. Zhang, Q. Li, Z.W. Liu, W.L. Mai, W. Chen, J. Lei, and H.K. Hu. 2019. miR-219a-5p ameliorates hepatic ischemia/reperfusion injury via impairing TP53BP2. Digestive Diseases and Sciences 64 (8): 2177–2186. https://doi.org/10.1007/s10620-019-05535-4.CrossRefPubMed

36.

Xin, S., and X. Ye. 2020. Oxalomalate regulates the apoptosis and insulin secretory capacity in streptozotocin-induced pancreatic beta-cells. Drug Development Research 81: 437–443. https://doi.org/10.1002/ddr.21635.CrossRefPubMed

37.

Zhang, M., A. Heldin, M. Palomar-Siles, S. Ohlin, V.J.N. Bykov, and K.G. Wiman. 2017. Synergistic rescue of nonsense mutant tumor suppressor p53 by combination treatment with aminoglycosides and Mdm2 inhibitors. Frontiers in Oncology 7: 323. https://doi.org/10.3389/fonc.2017.00323.CrossRefPubMed

38.

Zhang, Y., H.J. Zhang, Z.N. Zhang, S.Y. Li, W.J. Jiang, X. Li, and J.R. Lv. 2019. LncRNA MALAT1 cessation antagonizes hypoxia/reoxygenation injury in hepatocytes by inhibiting apoptosis and inflammation via the HMGB1-TLR4 axis. Molecular Immunology 112: 22–29. https://doi.org/10.1016/j.molimm.2019.04.015.CrossRefPubMed

39.

Zhao, G., X. Shen, H. Nan, L. Yan, H. Zhao, J. Yu, and Y. Lv. 2013. Remifentanil protects liver against ischemia/reperfusion injury through activation of anti-apoptotic pathways. The Journal of Surgical Research 183 (2): 827–834. https://doi.org/10.1016/j.jss.2013.02.058.CrossRefPubMed

40.

Zhao, L.Q., and Y.L. Li. 2020. Application of dexmedetomidine combined with sufentanil in colon cancer resection and its effect on immune and coagulation function of patients. Oncology Letters 20 (2): 1288–1294. https://doi.org/10.3892/ol.2020.11643.CrossRefPubMedPubMedCentral

41.

Zhou, H., Z.H. Zhu, Y. Liu, and Y.Y. Liu. 2020. Effects of midazolam combined with sufentanil on injury and expression of HMGB1 and NF-kappa B in rats with pancreatitis. European Review for Medical and Pharmacological Sciences 24 (4): 2102–2109.PubMed

42.

Zuo, Y.M., X.Q. Cheng, E.W. Gu, X.Q. Liu, L. Zhang, and Y.Y. Cao. 2014. Effect of aortic root infusion of sufentanil on ischemia-reperfusion injury in patients undergoing mitral valve replacement. Journal of Cardiothoracic and Vascular Anesthesia 28 (6): 1474–1478. https://doi.org/10.1053/j.jvca.2014.04.023.CrossRefPubMed

Title: Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression
Authors: Ling Zhou
Xinlu Yang
Shuhua Shu
Sheng Wang
Fenglin Guo
Ying Yin
Weide Zhou
Han Han
Xiaoqing Chai
Publication date: 01-06-2021
Publisher: Springer US
Keyword: Sufentanil
Published in: Inflammation / Issue 3/2021
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-020-01410-x

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Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression

Abstract

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Abstract

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