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Curcumin Alleviates β Amyloid-Induced Neurotoxicity in HT22 Cells via Upregulating SOD2

  • Shuping Du
  • Yuanyuan Zhang
  • Jing Yang
  • Xiaoyan Liu
  • Yuqing Wang
  • Bo XuEmail author
  • Ji JiaEmail author
Article

Abstract

Curcumin protects neuronal cells exposed to β amyloid (Aβ); the mechanism, however, is still obscure. The aim of this study is to determine whether the type 2 superoxide dismutase (SOD2) mediates curcumin-induced protective effects in Aβ-treated neuronal cells. In this study, the HT22 neuronal cells were exposed to Aβ to imitate neuronal injury in Alzheimer’s disease (AD). After 24-h treatment, 10 μM Aβ decreased cell viability and mitochondrial functions, including mitochondrial complex activities and mitochondrial membrane potential (MMP), and also downregulated anti-oxidants SOD2, glutathione (GSH), and catalase (CAT) levels (P < 0.05), meanwhile, increased lactic dehydrogenase (LDH) release, apoptosis level, intracellular reactive oxygen species (ROS) and mitochondrial superoxide accumulation (P < 0.05). And, co-administration of 1 μM curcumin significantly reduced the Aβ-induced cell injury and oxidative damage above (P < 0.05). Downregulating SOD2 by using small interfering RNA (siRNA), however, significantly abolished the curcumin-induced protective and anti-oxidative effects in HT22 cells (P < 0.05); the scramble (SC)-siRNA did not cause marked effects on the curcumin-induced protective effects (P > 0.05). These findings showed that curcumin can alleviate Aβ-induced injury in neuronal cells, and SOD2 protein may mediate the neuroprotective effects.

Keywords

Curcumin β amyloid SOD2 Alzheimer’s disease Neuroprotection 

Notes

Funding Information

This work was supported by the National Nature Science Foundation of China (61773130), Natural Science Foundation of Guangdong Province, China (2016A030313613), and the Science and Technology Program of Guangzhou, China (201707010027).

Compliance with Ethical Standards

Ethical Approval

All procedures were approved by the Ethics Committee of the General Hospital of Southern Theatre of PLA.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Alberdi E, Sánchez-Gómez MV, Ruiz A, Cavaliere F, Ortiz-Sanz C, Quintela-López T, Capetillo-Zarate E, Solé-Domènech S, Matute C (2018) Mangiferin and morin attenuate oxidative stress, mitochondrial dysfunction, and neurocytotoxicity, induced by amyloid beta oligomers. Oxidative Med Cell Longev 2018:2856063.  https://doi.org/10.1155/2018/2856063 CrossRefGoogle Scholar
  2. Anstey KJ, Peters R, Clare L, Lautenschlager NT, Dodge HH, Barnes DE, Shahar S, Brodaty H, Rees G (2017) Joining forces to prevent dementia: the international research network on dementia prevention (IRNDP). Int Psychogeriatr 29:1757–1760.  https://doi.org/10.1017/S1041610217001685 CrossRefGoogle Scholar
  3. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC, Dominantly Inherited Alzheimer Network (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367(9):795–804.  https://doi.org/10.1056/NEJMoa1202753 CrossRefGoogle Scholar
  4. Bature F, Guinn BA, Pang D, Pappas Y (2017) Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016. BMJ Open 7:e015746.  https://doi.org/10.1136/bmjopen-2016-015746 CrossRefGoogle Scholar
  5. Chan KY, Wang W, Wu JJ, Liu L, Theodoratou E, Car J, Middleton L, Russ TC, Deary IJ, Campbell H, Wang W, Rudan I, Global Health Epidemiology Reference Group (GHERG) (2013) Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990-2010: a systematic review and analysis. Lancet 381:2016–2023.  https://doi.org/10.1016/S0140-6736(13)60221-4 CrossRefGoogle Scholar
  6. Chuang KA, Li MH, Lin NH, Chang CH, Lu IH, Pan IH, Takahashi T, Perng MD, Wen SF (2017) Rhinacanthin C alleviates amyloid-β fibrils’ toxicity on neurons and attenuates neuroinflammation triggered by LPS, amyloid-β, and interferon-γ in glial cells. Oxidative Med Cell Longev 2017:5414297.  https://doi.org/10.1155/2017/5414297 Google Scholar
  7. Douglass BJ, Clouatre DL (2015) Beyond yellow curry: assessing commercial curcumin absorption technologies. J Am Coll Nutr 34:347–358.  https://doi.org/10.1080/07315724.2014.950392 CrossRefGoogle Scholar
  8. Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, Sur C, Mukai Y, Voss T, Furtek C, Mahoney E, Harper Mozley L, Vandenberghe R, Mo Y, Michelson D (2018) Randomized trial of verubecestat for mild-to-moderate Alzheimer’s disease. N Engl J Med 378:1691–1703.  https://doi.org/10.1056/NEJMoa1706441 CrossRefGoogle Scholar
  9. Fiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J (2007) Innate immunity and transcription of MGAT-III and toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci U S A 104:12849–11254.  https://doi.org/10.1073/pnas.0701267104 CrossRefGoogle Scholar
  10. Ginanneschi F, Filippou G, Bonifazi M, Frediani B, Rossi A (2014) Effects of local corticosteroid injection on electrical properties of aβ-fibers in carpal tunnel syndrome. J Mol Neurosci 52:525–530.  https://doi.org/10.1007/s12031-013-0107-4 CrossRefGoogle Scholar
  11. Gounden S, Chuturgoon A (2017) Curcumin upregulates antioxidant defense, lon protease, and heat-shock protein 70 under hyperglycemic conditions in human hepatoma cells. J Med Food 20:465–473.  https://doi.org/10.1089/jmf.2016.0146 CrossRefGoogle Scholar
  12. Han Z, Chen YR, Jones CI 3rd, Meenakshisundaram G, Zweier JL, Alevriadou BR (2007) Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex activities in cultured vascular endothelial cells. Am J Physiol Cell Physiol 292:C1103–C1112.  https://doi.org/10.1152/ajpcell.00389.2006 CrossRefGoogle Scholar
  13. Jia J, Ma L, Wu M, Zhang L, Zhang X, Zhai Q, Jiang T, Wang Q, Xiong L (2014) Anandamide protects HT22 cells exposed to hydrogen peroxide by inhibiting CB1 receptor-mediated type 2 NADPH oxidase. Oxidative Med Cell Longev 2014:893516.  https://doi.org/10.1155/2014/893516 CrossRefGoogle Scholar
  14. Joshi D, Mittal DK, Shukla S, Srivastav SK, Dixit VA (2017) Curcuma longa Linn. Extract and curcumin protect CYP 2E1 enzymatic activity against mercuric chloride-induced hepatotoxicity and oxidative stress: a protective approach. Exp Toxicol Pathol 69:373–382.  https://doi.org/10.1016/j.etp.2017.02.009 CrossRefGoogle Scholar
  15. Lee WH, Loo CY, Bebawy M, Luk F, Mason RS, Rohanizadeh R (2013) Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol 11:338–378.  https://doi.org/10.2174/1570159X11311040002 CrossRefGoogle Scholar
  16. Li L, Xiao L, Hou Y, He Q, Zhu J, Li Y, Wu J, Zhao J, Yu S, Zhao Y (2016) Sestrin2 silencing exacerbates cerebral ischemia/reperfusion injury by decreasing mitochondrial biogenesis through the AMPK/PGC-1α pathway in rats. Sci Rep 6:30272.  https://doi.org/10.1038/srep30272 CrossRefGoogle Scholar
  17. Ma L, Niu W, Yang S, Tian J, Luan H, Cao M, Xi W, Tu W, Jia J, Lv J (2018) Inhibition of mitochondrial permeability transition pore opening contributes to cannabinoid type 1 receptor agonist ACEA-induced neuroprotection. Neuropharmacology 135:211–222.  https://doi.org/10.1016/j.neuropharm.2018.03.024 CrossRefGoogle Scholar
  18. Nguyen CT, Sah SK, Zouboulis CC, Kim TY (2018) Inhibitory effects of superoxide dismutase 3 on Propionibacterium acnes-induced skin inflammation. Sci Rep 8:4024.  https://doi.org/10.1038/s41598-018-22132-z CrossRefGoogle Scholar
  19. Pari L, Tewas D, Eckel J (2008) Role of curcumin in health and disease. Arch Physiol Biochem 114:127–149.  https://doi.org/10.1080/13813450802033958 CrossRefGoogle Scholar
  20. Qin X, Qiao H, Wu S, Cheng J, Wan Q, Liu R (2018) Curcumin inhibits monocyte chemoattractant protein-1 expression in TNF-α induced astrocytes through AMPK pathway. Neurochem Res 43:775–784.  https://doi.org/10.1007/s11064-018-2479-x CrossRefGoogle Scholar
  21. Quinn JP, Corbett NJ, Kellett KAB, Hooper NM (2018) Tau proteolysis in the pathogenesis of tauopathies: neurotoxic fragments and novel biomarkers. J Alzheimers Dis 63:13–33.  https://doi.org/10.3233/JAD-170959 CrossRefGoogle Scholar
  22. Reddy PH, Manczak M, Yin X, Grady MC, Mitchell A, Tonk S, Kuruva CS, Bhatti JS, Kandimalla R, Vijayan M, Kumar S, Wang R, Pradeepkiran JA, Ogunmokun G, Thamarai K, Quesada K, Boles A, Reddy AP (2018) Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimers Dis 61:843–866.  https://doi.org/10.3233/JAD-170512 CrossRefGoogle Scholar
  23. Wu M, Jia J, Lei C, Ji L, Chen X, Sang H, Xiong L (2015) Cannabinoid receptor CB1 is involved in nicotine-induced protection against Aβ1-42 neurotoxicity in HT22 cells. J Mol Neurosci 55:778–787.  https://doi.org/10.1007/s12031-014-0422-4 CrossRefGoogle Scholar
  24. Xu P, Wang H, Li Z, Yang Z (2016) Triptolide attenuated injury via inhibiting oxidative stress in amyloid-Beta25-35-treated differentiated PC12 cells. Life Sci 145:19–26.  https://doi.org/10.1016/j.lfs.2015.12.018 CrossRefGoogle Scholar
  25. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280:5892–5901.  https://doi.org/10.1074/jbc.M404751200 CrossRefGoogle Scholar
  26. Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL (2018) Piper sarmentosum Roxb. Confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells. J Ethnopharmacol 217:187–194.  https://doi.org/10.1016/j.jep.2018.02.025 CrossRefGoogle Scholar
  27. Zhai X, Qiao H, Guan W, Li Z, Cheng Y, Jia X, Zhou Y (2015) Curcumin regulates peroxisome proliferator-activated receptor-γ coactivator-1α expression by AMPK pathway in hepatic stellate cells in vitro. Eur J Pharmacol 746:56–62.  https://doi.org/10.1016/j.ejphar.2014.10.055 CrossRefGoogle Scholar
  28. Zou J, Zhang S, Li P, Zheng X, Feng D (2018) Supplementation with curcumin inhibits intestinal cholesterol absorption and prevents atherosclerosis in high-fat diet-fed apolipoprotein E knockout mice. Nutr Res 56:32–40.  https://doi.org/10.1016/j.nutres.2018.04.017 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of AnesthesiologyWeihai Municipal HospitalWeihaiChina
  2. 2.Department of 1st GeriatricsGeneral Hospital of Southern Theatre Command of PLAGuangzhouChina
  3. 3.Southern Medical UniversityGuangzhouChina
  4. 4.Department of AnesthesiologyGeneral Hospital of Southern Theatre Command of PLAGuangzhouChina
  5. 5.Department of RehabilitationGeneral Hospital of Southern Theatre Command of PLAGuangzhouChina

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