DOI QR코드

DOI QR Code

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

  • Yeo, Eun Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Eum, Won Sik (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Yeo, Hyeon Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Yeon Joo (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Sohn, Eun Jeong (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kwon, Hyun Jung (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University) ;
  • Kim, Dae Won (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University) ;
  • Kim, Duk-Soo (Department of Anatomy and BK21 Plus Center, College of Medicine, Soonchunhyang University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Park, Jinseu (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Han, Kyu Hyung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Lee, Keun Wook (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Park, Jong Kook (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Shin, Min Jea (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
  • 투고 : 2020.09.03
  • 심사 : 2020.12.10
  • 발행 : 2021.05.01

초록

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

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참고문헌

  1. Ang, Y. L., Yong, W. P. and Tan, P. (2016) Translating gastric cancer genomics into targeted therapies. Crit. Rev. Oncol. Hematol. 100, 141-146. https://doi.org/10.1016/j.critrevonc.2016.02.007
  2. Angeloni, C., Motori, E., Fabbri, D., Malaguti, M., Leoncini, E., Lorenzini, A. and Hrelia, S. (2011) H2O2 preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation. Am. J. Physiol. Heart Circ. Physiol. 300, H2196-H2205. https://doi.org/10.1152/ajpheart.00934.2010
  3. Booze, M. L., Hansen, J. M. and Vitiello, P. F. (2016) A novel mouse model for the identification of thioredoxin-1 protein interactions. Free Radic. Biol. Med. 99, 533-543. https://doi.org/10.1016/j.freeradbiomed.2016.09.013
  4. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254. https://doi.org/10.1006/abio.1976.9999
  5. Chan, P. H. (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J. Cereb. Blood Flow Metab. 21, 2-14. https://doi.org/10.1097/00004647-200101000-00002
  6. Chen, Y. and Swanson, R. A. (2003) Astrocytes and brain injury. J. Cereb. Blood Flow Metab. 23, 137-149. https://doi.org/10.1097/01.WCB.0000044631.80210.3C
  7. Das, K. C. and Das, C. K. (2000) Thioredoxin, a singlet oxygen quencher and hydroxyl radical scavenger: redox independent functions. Biochem. Biophys. Res. Commun. 277, 443-447. https://doi.org/10.1006/bbrc.2000.3689
  8. Embury, J., Klein, D., Pileggi, A., Ribeiro, M., Jayaraman, S., Molano, R. D., Fraker, C., Kenyon, N., Ricordi, C., Inverardi, L. and Pastori, R. L. (2001) Proteins linked to a protein transduction domain efficiently transduce pancreatic islets. Diabetes 50, 1706-1713. https://doi.org/10.2337/diabetes.50.8.1706
  9. Floyd, R. A. (1990) Role of oxygen free radicals in carcinogenesis and brain ischemia. FASEB J. 4, 2587-2597. https://doi.org/10.1096/fasebj.4.9.2189775
  10. Fujino, G., Noguchi, T., Matsuzawa, A., Yamauchi, S., Saitoh, M., Takeda, K. and Ichijo, H. (2007) Thioredoxin and TRAF family proteins regulate reactive oxygen species-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1. Mol. Cell Biol. 27, 8152-8163. https://doi.org/10.1128/MCB.00227-07
  11. Ginsberg, M. D., Becker, D. A., Busto, R., Belayev, A., Zhang, Y., Khoutorova, L., Ley, J. J., Zhao, W. and Belayev, L. (2003) Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. Ann. Neurol. 54, 330-342. https://doi.org/10.1002/ana.10659
  12. Haendeler, J., Hoffmann, J., Tischler, V., Berk, B. C., Zeiher, A. M. and Dimmeler, S. (2002) Redox regulatory and anti-apoptotic functions of thioredoxin depend on S-nitrosylation at cysteine 69. Nat. Cell Biol. 4, 743-749. https://doi.org/10.1038/ncb851
  13. Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K. and Gotoh, Y. (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275, 90-94. https://doi.org/10.1126/science.275.5296.90
  14. Ito, D., Tanaka, K., Suzuki, S., Dembo, T. and Fukuuchi, Y. (2001) Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain. Stroke 32, 1208-1215. https://doi.org/10.1161/01.str.32.5.1208
  15. Janac, B., Radenovic, L., Selakovic, V. and Prolic, Z. (2006) Time course of motor behavior changes in Mongolian gerbils submitted to different durations of cerebral ischemia. Behav. Brain Res. 175, 362-373. https://doi.org/10.1016/0006-8993(79)91017-5
  16. Jegal, M. E., Jung, S. Y., Han, Y. S. and Kim, Y. J. (2019) C-terminal truncated HBx reduces doxorubicin cytotoxicity via ABCB1 upregulation in Huh-7 hepatocellular carcinoma cells. BMB Rep. 52, 330-335. https://doi.org/10.5483/bmbrep.2019.52.5.312
  17. Jellinger, K. A. and Stadelmann, C. (2001) Problems of cell death in neurodegeneration and Alzheimer's disease. J. Alzheimers Dis. 3, 31-40. https://doi.org/10.3233/JAD-2001-3106
  18. Jia, L., Chen, Y., Tian, Y. H. and Zhang, G. (2018) MAPK pathway mediates the anti-oxidative effect of chicoric acid against cerebral ischemia-reperfusion injury in vivo. Exp. Ther. Med. 15, 1640-1646.
  19. Kaimul Ahsan, M., Nakamura, H., Tanito, M., Yamada, K., Utsumi, H. and Yodoi, J. (2005) Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP-induced down-regulation of Akt. Free Radic. Biol. Med. 39, 1549-1559. https://doi.org/10.1016/j.freeradbiomed.2005.07.016
  20. Kamimoto, Y., Sugiyama, T., Kihira, T., Zhang, L., Murabayashi, N., Umekawa, T., Nagao, K., Ma, N., Toyoda, N., Yodoi, J. and Sagawa, N. (2010) Transgenic mice overproducing human thioredoxin-1, an antioxidative and anti-apoptotic protein, prevents diabetic embryopathy. Diabetologia 53, 2046-2055. https://doi.org/10.1007/s00125-010-1784-y
  21. Kim, D. H., Kim, H. M., Huong, P. T. T., Han, H. J., Hwang, J., Cha-Molstad, H., Lee, K. H., Ryoo, I. J., Kim, K. E., Huh, Y. H., Ahn, J. S., Kwon, Y. T., Soung, N. K. and Kim, B. Y. (2019) Enhanced anticancer effects of a methylation inhibitor by inhibiting a novel DNMT1 target, CEP 131, in cervical cancer. BMB Rep. 52, 342-347. https://doi.org/10.5483/bmbrep.2019.52.5.055
  22. Kim, D. W., Shin, M. J., Choi, Y. J., Kwon, H. J., Lee, S. H., Lee, S., Park, J., Han, K. H., Eum, W. S. and Choi, S. Y. (2018) Tat-ATOX1 inhibits inflammatory responses via regulation of MAPK and NFkappaB pathways. BMB Rep. 51, 654-659. https://doi.org/10.5483/BMBRep.2018.51.12.248
  23. Kim, E. K. and Choi, E. J. (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta 1802, 396-405. https://doi.org/10.1016/j.bbadis.2009.12.009
  24. Kim, H. L., Koedrith, P., Lee, S. M., Kim, Y. J. and Seo, Y. R. (2013) Base excision DNA repair defect in thioredoxin-1 (Trx1)-deficient cells. Mutat. Res. 751-752, 1-7. https://doi.org/10.1016/j.mrfmmm.2013.10.002
  25. Kim, H. R., Kim, D. W., Jo, H. S., Cho, S. B., Park, J. H., Lee, C. H., Choi, Y. J., Yeo, E. J., Park, S. Y., Kim, S. T., Yu, Y. H., Kim, D. S., Kim, H. A., Cho, S. W., Han, K. H., Park, J., Eum, W. S. and Choi, S. Y. (2015) Tat-biliverdin reductase A inhibits inflammatory response by regulation of MAPK and NF-kappaB pathways in Raw 264.7 cells and edema mouse model. Mol. Immunol. 63, 355-366. https://doi.org/10.1016/j.molimm.2014.09.003
  26. Kubo, E., Fatma, N., Akagi, Y., Beier, D. R., Singh, S. P. and Singh, D. P. (2008) TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity. Am. J. Physiol. Cell Physiol. 294, C842-C855. https://doi.org/10.1152/ajpcell.00540.2007
  27. Kwon, S. H., Hong, S. I., Kim, J. A., Jung, Y. H., Kim, S. Y., Kim, H. C., Lee, S. Y. and Jang, C. G. (2011) The neuroprotective effects of Lonicera japonica THUNB. against hydrogen peroxide-induced apoptosis via phosphorylation of MAPKs and PI3K/Akt in SH-SY5Y cells. Food Chem. Toxicol. 49, 1011-1019. https://doi.org/10.1016/j.fct.2011.01.008
  28. Leak, R. K., Li, P., Zhang, F., Sulaiman, H. H., Weng, Z., Wang, G., Stetler, R. A., Shi, Y., Cao, G., Gao, Y. and Chen, J. (2015) Apurinic/apyrimidinic endonuclease 1 upregulation reduces oxidative DNA damage and protects hippocampal neurons from ischemic injury. Antioxid. Redox Signal. 22, 135-148. https://doi.org/10.1089/ars.2013.5511
  29. Lee, K. W., Zhao, X., Im, J. Y., Grosso, H., Jang, W. H., Chan, T. W., Sonsalla, P. K., German, D. C., Ichijo, H., Junn, E. and Mouradian, M. M. (2012) Apoptosis signal-regulating kinase 1 mediates MPTP toxicity and regulates glial activation. PLoS ONE 7, e29935. https://doi.org/10.1371/journal.pone.0029935
  30. Li, Y., Xu, B., Xu, M., Chen, D., Xiong, Y., Lian, M., Sun, Y., Tang, Z., Wang, L., Jiang, C. and Lin, Y. (2017) 6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-kappaB signalling. Pharmacol. Res. 119, 137-148. https://doi.org/10.1016/j.phrs.2017.01.026
  31. Li, Y. and Zhang, Z. (2015) Gastrodin improves cognitive dysfunction and decreases oxidative stress in vascular dementia rats induced by chronic ischemia. Int. J. Clin. Exp. Pathol. 8, 14099-14109.
  32. Li, Z., Wang, Y., Xie, Y., Yang, Z. and Zhang, T. (2011) Protective effects of exogenous hydrogen sulfide on neurons of hippocampus in a rat model of brain ischemia. Neurochem. Res. 36, 1840-1849. https://doi.org/10.1007/s11064-011-0502-6
  33. Luo, P., Lu, Y., Li, C., Zhou, M., Chen, C., Lu, Q., Xu, X., He, Z. and Guo, L. (2015) Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region. Neurobiol. Learn. Mem. 123, 72-83. https://doi.org/10.1016/j.nlm.2015.05.005
  34. Mansour, A., Niizuma, K., Rashad, S., Sumiyoshi, A., Ryoke, R., Endo, H., Endo, T., Sato, K., Kawashima, R. and Tominaga, T. (2019) A refined model of chronic cerebral hypoperfusion resulting in cognitive impairment and a low mortality rate in rats. J. Neurosurg. 131, 892-902. https://doi.org/10.3171/2018.3.jns172274
  35. Mates, J. M., Segura, J. A., Alonso, F. J. and Marquez, J. (2012) Oxidative stress in apoptosis and cancer: an update. Arch. Toxicol. 86, 1649-1665. https://doi.org/10.1007/s00204-012-0906-3
  36. Mehla, J., Lacoursiere, S., Stuart, E., McDonald, R. J. and Mohajerani, M. H. (2018) Gradual cerebral hypoperfusion impairs fear conditioning and object recognition learning and memory in mice: potential roles of neurodegeneration and cholinergic dysfunction. J. Alzheimers Dis. 61, 283-293.
  37. Meuillet, E. J., Mahadevan, D., Berggren, M., Coon, A. and Powis, G. (2004) Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN's lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN's tumor suppressor activity. Arch. Biochem. Biophys. 429, 123-133. https://doi.org/10.1016/j.abb.2004.04.020
  38. Miki, K., Ishibashi, S., Sun, L., Xu, H., Ohashi, W., Kuroiwa, T. and Mizusawa, H. (2009) Intensity of chronic cerebral hypoperfusion determines white/gray matter injury and cognitive/ motor dysfunction in mice. J. Neurosci. Res. 87, 1270-1281. https://doi.org/10.1002/jnr.21925
  39. Mo, L., Yang, C., Gu, M., Zheng, D., Lin, L., Wang, X., Lan, A., Hu, F. and Feng, J. (2012) PI3K/Akt signaling pathway-induced heme oxygenase-1 upregulation mediates the adaptive cytoprotection of hydrogen peroxide preconditioning against oxidative injury in PC12 cells. Int. J. Mol. Med. 30, 314-320. https://doi.org/10.3892/ijmm.2012.1002
  40. Nadeau, P. J., Charette, S. J., Toledano, M. B. and Landry, J. (2007) Disulfide Bond-mediated multimerization of Ask1 and its reduction by thioredoxin-1 regulate H2O2-induced c-Jun NH2-terminal kinase activation and apoptosis. Mol. Biol. Cell 18, 3903-3913. https://doi.org/10.1091/mbc.E07-05-0491
  41. Nakamura, H., Masutani, H. and Yodoi, J. (2006) Extracellular thioredoxin and thioredoxin-binding protein 2 in control of cancer. Semin. Cancer Biol. 16, 444-451. https://doi.org/10.1016/j.semcancer.2006.09.001
  42. Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K. and Ichijo, H. (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 17, 2596-2606. https://doi.org/10.1093/emboj/17.9.2596
  43. Schwarze, S. R., Ho, A., Vocero-Akbani, A. and Dowdy, S. F. (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569-1572. https://doi.org/10.1126/science.285.5433.1569
  44. Shibata, M., Ohtani, R., Ihara, M., Tomimoto, H. (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35, 2598-2603. https://doi.org/10.1161/01.str.0000143725.19053.60
  45. Shiizaki, S., Naguro, I. and Ichijo, H. (2013) Activation mechanisms of ASK1 in response to various stresses and its significance in intracellular signaling. Adv. Biol. Regul. 53, 135-144. https://doi.org/10.1016/j.jbior.2012.09.006
  46. Shin, M. J., Kim, D. W., Lee, Y. P., Ahn, E. H., Jo, H. S., Kim, D. S., Kwon, O. S., Kang, T. C., Cho, Y. J., Park, J., Eum, W. S. and Choi, S. Y. (2014) Tat-glyoxalase protein inhibits against ischemic neuronal cell damage and ameliorates ischemic injury. Free Radic. Biol. Med. 67, 195-210. https://doi.org/10.1016/j.freeradbiomed.2013.10.815
  47. Sinha, K., Das, J., Pal, P. B. and Sil, P. C. (2013) Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch. Toxicol. 87, 1157-1180. https://doi.org/10.1007/s00204-013-1034-4
  48. Stosic-Grujicic, S., Stojanovic, I., Maksimovic-Ivanic, D., Momcilovic, M., Popadic, D., Harhaji, L., Miljkovic, D., Metz, C., Mangano, K., Papaccio, G., Al-Abed, Y. and Nicoletti, F. (2008) Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus. J. Cell. Physiol. 215, 665-675. https://doi.org/10.1002/jcp.21346
  49. Sugawara, T. and Chan, P. H. (2003) Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid. Redox Signal. 5, 597-607. https://doi.org/10.1089/152308603770310266
  50. Susanti, D., Wong, J. H., Vensel, W. H., Loganathan, U., DeSantis, R., Schmitz, R. A., Balsera, M., Buchanan, B. B. and Mukhopadhyay, B. (2014) Thioredoxin targets fundamental processes in a methane-producing archaeon, Methanocaldococcus jannaschii. Proc. Natl. Acad. Sci. U.S.A. 111, 2608-2613. https://doi.org/10.1073/pnas.1324240111
  51. Tao, L., Gao, E., Bryan, N. S., Qu, Y., Liu, H. R., Hu, A., Christopher, T. A., Lopez, B. L., Yodoi, J., Koch, W. J., Feelisch, M. and Ma, X. L. (2004) Cardioprotective effects of thioredoxin in myocardial ischemia and reperfusion: role of S-nitrosation [corrected]. Proc. Natl. Acad. Sci. U.S.A. 101, 11471-11476. https://doi.org/10.1073/pnas.0402941101
  52. Ueda, S., Masutani, H., Nakamura, H., Tanaka, T., Ueno, M. and Yodoi, J. (2002) Redox control of cell death. Antioxid. Redox Signal. 4, 405-414. https://doi.org/10.1089/15230860260196209
  53. van den Berg, A. and Dowdy, S. F. (2011) Protein transduction domain delivery of therapeutic macromolecules. Curr. Opin. Biotechnol. 22, 888-893. https://doi.org/10.1016/j.copbio.2011.03.008
  54. Wadia, J. S. and Dowdy, S. F. (2002) Protein transduction technology. Curr. Opin. Biotechnol. 13, 52-56. https://doi.org/10.1016/S0958-1669(02)00284-7
  55. Wang, M., Zhu, K., Zhang, L., Li, L. and Zhao, J. (2016) Thioredoxin 1 protects astrocytes from oxidative stress by maintaining peroxiredoxin activity. Mol. Med. Rep. 13, 2864-2870. https://doi.org/10.3892/mmr.2016.4855
  56. Wu, X., Li, L., Zhang, L., Wu, J., Zhou, Y., Zhou, Y., Zhao, Y. and Zhao, J. (2015) Inhibition of thioredoxin-1 with siRNA exacerbates apoptosis by activating the ASK1-JNK/p38 pathway in brain of a stroke model rats. Brain Res. 1599, 20-31. https://doi.org/10.1016/j.brainres.2014.12.033
  57. Yamamoto, M., Yamato, E., Toyoda, S., Tashiro, F., Ikegami, H., Yodoi, J. and Miyazaki, J. (2008) Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus. Antioxid. Redox Signal. 10, 43-49. https://doi.org/10.1089/ars.2007.1586
  58. Yano, S., Morioka, M., Fukunaga, K., Kawano, T., Hara, T., Kai, Y., Hamada, J., Miyamoto, E. and Ushio, Y. (2001) Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus. J. Cereb. Blood Flow Metab. 21, 351-360. https://doi.org/10.1097/00004647-200104000-00004
  59. Yeo, H., Yeo, E. J., Shin, M. J., Choi, Y. J., Lee, C. H., Kwon, H. Y., Kim, D. W., Eum, W. S. and Choi, S. Y. (2018) Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in a mice model. BMB Rep. 51, 362-367. https://doi.org/10.5483/BMBRep.2018.51.7.101
  60. Yeo, H. J., Shin, M. J., Yeo, E. J., Choi, Y. J., Kim, D. W., Kim, D. S., Eum, W. S. and Choi, S. Y. (2019) Tat-CIAPIN1 inhibits hippocampal neuronal cell damage through the MAPK and apoptotic signaling pathways. Free Radic. Biol. Med. 135, 68-78. https://doi.org/10.1016/j.freeradbiomed.2019.02.028
  61. Yoo, M. H., Carlson, B. A., Gladyshev, V. N. and Hatfield, D. L. (2013) Abrogated thioredoxin system causes increased sensitivity to TNF-alpha-induced apoptosis via enrichment of p-ERK 1/2 in the nucleus. PLoS ONE 8, e71427. https://doi.org/10.1371/journal.pone.0071427
  62. Yoshida, T., Oka, S., Masutani, H., Nakamura, H. and Yodoi, J. (2003) The role of thioredoxin in the aging process: involvement of oxidative stress. Antioxid. Redox Signal. 5, 563-570. https://doi.org/10.1089/152308603770310211
  63. Yoshizaki, K., Adachi, K., Kataoka, S., Watanabe, A., Tabira, T., Takahashi, K. and Wakita, H. (2008) Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice. Exp. Neurol. 210, 585-591. https://doi.org/10.1016/j.expneurol.2007.12.005
  64. Yu, H., Shi, L., Qi, G., Zhao, S., Gao, Y. and Li, Y. (2016) Gypenoside Protects cardiomyocytes against ischemia-reperfusion injury via the inhibition of mitogen-activated protein kinase mediated nuclear factor kappa B pathway in vitro and in vivo. Front. Pharmacol. 7, 148.
  65. Zhang, J., Xia, J., Zhang, Y., Xiao, F., Wang, J., Gao, H., Liu, Y., Rong, S., Yao, Y., Xu, G. and Li, J. (2016) HMGB1-TLR4 signaling participates in renal ischemia reperfusion injury and could be attenuated by dexamethasone-mediated inhibition of the ERK/NF-kappaB pathway. Am. J. Transl. Res. 8, 4054-4067.
  66. Zhang, R., Al-Lamki, R., Bai, L., Streb, J. W., Miano, J. M., Bradley, J. and Min, W. (2004) Thioredoxin-2 inhibits mitochondria-located ASK1-mediated apoptosis in a JNK-independent manner. Circ. Res. 94, 1483-1491. https://doi.org/10.1161/01.RES.0000130525.37646.a7
  67. Zhu, N., Cai, C., Zhou, A., Zhao, X., Xiang, Y. and Zeng, C. (2017) Schisandrin B prevents hind limb from ischemia-reperfusion-induced oxidative stress and inflammation via mapk/nf-kappaB pathways in rats. Biomed. Res. Int. 2017, 4237973.