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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Anti-inflammatory and anti-oxidative effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on β-amyloid-induced microglial activation

  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University) ;
  • Kim, Jiae (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Lee, Sang Eun (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Ahn, Jee-Yin (Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
  • Received : 2017.09.22
  • Accepted : 2017.10.12
  • Published : 2017.12.31
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Abstract

We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid ${\beta}$ ($A{\beta}$)-treated primary microglial cells. KHG26792 attenuated the $A{\beta}-induced$ production of inflammatory mediators such as IL-6, $IL-1{\beta}$, $TNF-{\alpha}$, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by $A{\beta}$ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the $A{\beta}-induced$ increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of $Akt/GSK-3{\beta}$ signaling and by decreasing the $A{\beta}-induced$ translocation of $NF-{\kappa}B$. Our results provide novel insights into the use of KHG26792 as a potential agent against $A{\beta}$ toxicity, including its role in the reduction of inflammation and oxidative stress. Nevertheless, further investigations of cellular signaling are required to clarify the in vivo effects of KHG26792 against $A{\beta}-induced$ toxicity.

Keywords

References

  1. Cerpa W, Dinamarca MC and Inestrosa NC (2008) Structure-function implications in Alzheimer's disease: effect of Abeta oligomers at central synapses, Curr Alzheimer Res 5, 233-243 https://doi.org/10.2174/156720508784533321
  2. Li J, Yang JY, Yao XC et al (2013) Oligomeric $A{\beta}$-induced microglial activation is possibly mediated by NADPH oxidase. Neurochem Res 38, 443-452 https://doi.org/10.1007/s11064-012-0939-2
  3. Guo Y, Shi S, Tang M et al (2014) The suppressive effects of gx-50 on $A{\beta}$-induced chemotactic migration of microglia. Int Immunopharmacol 19, 283-289 https://doi.org/10.1016/j.intimp.2014.01.025
  4. Mosher KI and Wyss-Coray T (2014) Microglial dysfunction in brain aging and Alzheimer's disease. Biochem Pharmacol 88, 594-604
  5. Krementsov DN, Thornton TM, Teuscher C and RinconM (2013) The emerging role of p38 mitogen-activated protein kinase in multiple sclerosis and its models. Mol Cell Biol 33, 3728-3734 https://doi.org/10.1128/MCB.00688-13
  6. Lowe JT, Lee MD, Akella LB et al (2012) Synthesis and profiling of a diverse collection of azetidine-based scaffolds for the development of CNS-focused lead-like libraries. J Org Chem 77, 7187-7211 https://doi.org/10.1021/jo300974j
  7. Dalla Y, Singh N, Jaggi AS, Singh D and Ghulati P (2009) Potential of ezetimibe in memory deficits associated with dementia of Alzheimer's type in mice. Indian J Pharmacol 41, 262-267 https://doi.org/10.4103/0253-7613.59925
  8. Han M, Song C, Jeong N and Hahn HG (2014). Exploration of 3-aminoazetidines as triple reuptake inhibitors by bioisosteric modification of 3-aoxyazetidine. ACS Med Chem Lett 5, 999-1004 https://doi.org/10.1021/ml500187a
  9. Yun J, Han M, Song C, Cheon SH, Choi K and Hahn HG (2014) Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors. Bioorg Med Chem Lett 24, 3234-3237 https://doi.org/10.1016/j.bmcl.2014.06.026
  10. Kim EA, Cho CH, Kim J et al (2015) The azetidine derivative, KHG26792 protects against ATP-induced activation of NFAT and MAPK pathways through P2X7 receptor in microglia. Neurotoxicology 51, 198-206 https://doi.org/10.1016/j.neuro.2015.10.013
  11. Kim J, Kim SM, Na JM, Hahn HG, Cho SW and Yang SJ (2016) Protective effect of 3-(naphthalen-2-yl(propoxy) methyl)azetidine hydrochloride on hypoxia-induced toxicity by suppressing microglial activation in BV-2 cells. BMB Rep 49, 687-692 https://doi.org/10.5483/BMBRep.2016.49.12.169
  12. Ebert S, Gerber J, Bader S et al (2005) Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J Neuroimmunol 159, 87-96 https://doi.org/10.1016/j.jneuroim.2004.10.005
  13. Bach JP, Mengel D, Wahle T et al (2011) The role of CNI-1493 in the function of primary microglia with respect to amyloid-beta. J Alzheimers Dis 26, 69-80 https://doi.org/10.3233/JAD-2011-110179
  14. Shahani N and Sawa A (2011) Nitric oxide signaling and nitrosative stress in neurons: role for S-nitrosylation. Antioxid Redox Signal 14, 1493-1504 https://doi.org/10.1089/ars.2010.3580
  15. Tayler H, Fraser T, Miners JS, Kehoe PG and Love S (2010) Oxidative balance in Alzheimer's disease: Relationship to APOE, Braak tangle stage, and the concentrations of soluble and insoluble amyloid-${\beta}$. J Alzheimers Dis 22, 1363-1373
  16. Butterfield DA and Lauderback CM (2002) Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide associated free radical oxidative stress. Free Radic Biol Med 32, 1050-1060 https://doi.org/10.1016/S0891-5849(02)00794-3
  17. Sultana R, Ravagna A, Mohmmad-Abdul H, Calabrese V and Butterfield DA (2005) Ferulic acid ethyl ester protects neurons against amyloid beta-peptide(1-42)-induced oxidative stress and neurotoxicity: relationship to antioxidant activity. J Neurochem 92, 749-758 https://doi.org/10.1111/j.1471-4159.2004.02899.x
  18. Qureshi GA, Baig S, Sarwar M and Parvez SH (2004) Neurotoxicity, oxidative stress and cerebrovascular disorders. Neurotoxicology 25, 121-138 https://doi.org/10.1016/S0161-813X(03)00093-7
  19. Chen JX and Yan SS (2010) Role of mitochondrial amyloid-beta in Alzheimer's disease. J Alzheimers Dis 20, S569-S578 https://doi.org/10.3233/JAD-2010-100357
  20. Part K, Kunnis-Beres K, Poska H, Land T, Shimmo R and Fernaeus SZ (2015) Amyloid ${\beta}_{25-35}$ induced ROS-burst through NADPH oxidase is sensitive to iron chelation in microglial Bv2 cells. Brain Res 1629, 282-290 https://doi.org/10.1016/j.brainres.2015.09.034
  21. Yao Y, Li J, Niu Y et al (2015) Resveratrol inhibits oligomeric $A{\beta}$-induced microglial activation via NADPH oxidase. Mol Med Rep 12, 6133-6139 https://doi.org/10.3892/mmr.2015.4199
  22. Hernandez F, Lucas JJ and Avila J (2013) GSK3 and tau: two convergence points in Alzheimer's disease. J Alzheimers Dis 33, S141-S144
  23. Zou Y, Hong B, Fan L et al (2013) Protective effect of puerarin against beta-amyloid-induced oxidative stress in neuronal cultures from rat hippocampus: involvement of the GSK-$3{\beta}$/Nrf2 signaling pathway. Free Radic Res 47, 55-63 https://doi.org/10.3109/10715762.2012.742518
  24. Dobarro M, Gerenu G and Ramirez MJ (2013) Propranolol reduces cognitive deficits, amyloid and tau pathology in Alzheimer's transgenic mice. Int J Neuropsychopharmacol 16, 2245-2257 https://doi.org/10.1017/S1461145713000631
  25. Terai K, Matsuo A and McGeer PL (1996) Enhancement of immunoreactivity for NF-kappaB in the hippocampal formation and cerebral cortex of Alzheimer's disease. Brain Res 735, 159-168 https://doi.org/10.1016/0006-8993(96)00310-1
  26. Zhang J, Zhen YF, Pu-Bu-Ci-Ren et al (2013) Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stress and inflammatory mediators in rat hippocampus. Behav Brain Res 244, 70-81 https://doi.org/10.1016/j.bbr.2013.01.037
  27. Zhu X, Rottkamp CA, Hartzler A et al (2001) Activation of MKK6, an upstream activator of p38, in Alzheimer's disease. J Neurochem 79, 311-318
  28. Han Y, Han M, Shin D, Song C and Hahn HG (2012) Exploration of novel 3-substituted azetidine derivatives as triple reuptake inhibitors. J Med Chem 55, 8188-8192 https://doi.org/10.1021/jm3008294
  29. Kim SJ, Cha JY, Kang HS et al (2016) Corosolic acid ameliorates acute inflammation through inhibition of IRAK-1 phosphorylation in macrophages. BMB Rep 49, 276-281 https://doi.org/10.5483/BMBRep.2016.49.5.241
  30. Reznick AZ and Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233, 357-363
  31. Lauderback CM, Hackett JM, Huang FF et al (2001) The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of amyloid beta (1-42). J Neurochem 78, 413-416 https://doi.org/10.1046/j.1471-4159.2001.00451.x
  32. Li MH, Jang JH, Sun B and Surh YJ (2004) Protective effects of oligomers of grape seed polyphenols against beta-amyloid induced oxidative cell death. Ann NY Acad Sci 1030, 317-329 https://doi.org/10.1196/annals.1329.040

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