Advertisement

Mitochondrial Protection Promoted by the Coffee Diterpene Kahweol in Methylglyoxal-Treated Human Neuroblastoma SH-SY5Y Cells

  • Marcos Roberto de OliveiraEmail author
  • Izabel Cristina Custódio de Souza
  • Cristina Ribas Fürstenau
Original Article

Abstract

The coffee diterpene kahweol (KW; C20H26O3) is a cytoprotective agent exhibiting potent antioxidant actions, as demonstrated in several experimental models. In spite of the efforts to elucidate exactly how KW promotes cytoprotection, it was not previously examined whether KW would be able to protect mitochondria of human cells undergoing redox stress. In the present work, we have treated the human neuroblastoma SH-SY5Y cell line with KW at 0.1–10 μM for 12 h prior to a challenge with methylglyoxal (MG), a reactive dicarbonyl that impairs mitochondrial function. We have found that KW at 10 μM suppressed the loss of mitochondrial membrane potential (MMP) and the bioenergetics decline (including decreased activity of the mitochondrial complexes I and V and reduced production of adenosine triphosphate, ATP) in the MG-treated SH-SY5Y cells. KW also prevented the MG-elicited generation of reactive oxygen and nitrogen species (ROS and RNS, respectively) in the SH-SY5Y cells. In this regard, KW exerted an antioxidant effect on the membranes of mitochondria obtained from the MG-treated cells. The mitochondria-related effects induced by KW were blocked by inhibition of the phosphoinositide 3-kinase (PI3K)/Akt or of the p38 mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, silencing of the transcription factor nuclear factor E2-related factor 2 (Nrf2) suppressed the mitochondrial protection promoted by KW in the MG-challenged cells. Therefore, KW protected mitochondria by a mechanism associated with the PI3K/Akt and p38 MAPK/Nrf2 signaling pathways.

Keywords

Kahweol Mitochondria Methylglyoxal Cytoprotection Antioxidant Nrf2 

Notes

Acknowledgments

MRO receives a “Bolsa de Produtividade em Pesquisa 2-PQ2” fellow from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (protocol number 301273/2018-9). This research was supported by CNPq (protocol numbers 400216/2016-7 and 460903/2014-4).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_107_MOESM1_ESM.pdf (131 kb)
Figure S1 The effects of methylglyoxal (MG) and/or kahweol (KW) on the release of cytochrome c to the cytosol (A), caspase-9 activity (B), caspase-3 activity (C), DNA fragmentation levels (D), and cleaved PARP levels (E) in SH-SY5Y cells. KW at 10 μM was administrated to the cells for 12 h prior to the exposure to MG at 500 μM for further 24 h. Data are demonstrated as the mean ± SD of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 vs control cells, #p < 0.05 vs MG-treated cells. (PDF 130 kb)
12640_2019_107_MOESM2_ESM.pdf (50 kb)
Figure S2 The effects of the transfection with small interfering RNA (siRNA) targeting Nrf2 on the nuclear content of Nrf2 in SH-SY5Y cells treated with kahweol (KW). Nrf2 was silenced by using small interfering RNA (siRNA) for 48 h before KW treatment. Data are demonstrated as the mean ± SD of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 vs control cells transfected with negative control (NC) siRNA; #p < 0.05 vs the kahweol-treated cells transfected with NC siRNA. (PDF 49 kb)

References

  1. Ahmed N, Battah S, Karachalias N, Babaei-Jadidi R, Horányi M, Baróti K, Hollan S, Thornalley PJ (2003) Increased formation of methylglyoxal and protein glycation, oxidation and nitrosation in triosephosphate isomerase deficiency. Biochim Biophys Acta 1639:121–132CrossRefGoogle Scholar
  2. Allaman I, Bélanger M, Magistretti PJ (2015) Methylglyoxal, the dark side of glycolysis. Front Neurosci 9:23.  https://doi.org/10.3389/fnins.2015.00023 CrossRefGoogle Scholar
  3. Anderson G, Maes M (2014) Neurodegeneration in Parkinson's disease: interactions of oxidative stress, tryptophan catabolites and depression with mitochondria and sirtuins. Mol Neurobiol 49:771–783.  https://doi.org/10.1007/s12035-013-8554-z CrossRefGoogle Scholar
  4. Angeloni C, Malaguti M, Rizzo B, Barbalace MC, Fabbri D, Hrelia S (2015) Neuroprotective effect of sulforaphane against methylglyoxal cytotoxicity. Chem Res Toxicol 28:1234–1245.  https://doi.org/10.1021/acs.chemrestox.5b00067 CrossRefGoogle Scholar
  5. Battino M, Giampieri F, Pistollato F, Sureda A, de Oliveira MR, Pittalà V, Fallarino F, Nabavi SF, Atanasov AG, Nabavi SM (2018) Nrf2 as regulator of innate immunity: a molecular Swiss army knife! Biotechnol Adv 36:358–370.  https://doi.org/10.1016/j.biotechadv.2017.12.012 CrossRefGoogle Scholar
  6. Brown GC, Bal-Price A (2003) Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol Neurobiol 27:325–355CrossRefGoogle Scholar
  7. Cárdenas C, Quesada AR, Medina MÁ (2014) Insights on the antitumor effects of kahweol on human breast cancer: decreased survival and increased production of reactive oxygen species and cytotoxicity. Biochem Biophys Res Commun 447:452–458.  https://doi.org/10.1016/j.bbrc.2014.04.026 CrossRefGoogle Scholar
  8. Chun HJ, Lee Y, Kim AH, Lee J (2016) Methylglyoxal causes cell death in neural progenitor cells and impairs adult hippocampal neurogenesis. Neurotox Res 29:419–431.  https://doi.org/10.1007/s12640-015-9588-y CrossRefGoogle Scholar
  9. de Oliveira MR (2015) Vitamin a and Retinoids as mitochondrial toxicants. Oxidative Med Cell Longev 2015:140267–140213.  https://doi.org/10.1155/2015/140267 CrossRefGoogle Scholar
  10. de Oliveira MR (2016) Fluoxetine and the mitochondria: a review of the toxicological aspects. Toxicol Lett 258:185–191.  https://doi.org/10.1016/j.toxlet.2016.07.001 CrossRefGoogle Scholar
  11. de Oliveira MR, Jardim FR (2016) Cocaine and mitochondria-related signaling in the brain: a mechanistic view and future directions. Neurochem Int 92:58–66.  https://doi.org/10.1016/j.neuint.2015.12.006 CrossRefGoogle Scholar
  12. de Oliveira MR, Lorenzi R, Schnorr CE, Morrone M, Moreira JC (2011) Increased 3-nitrotyrosine levels in mitochondrial membranes and impaired respiratory chain activity in brain regions of adult female rats submitted to daily vitamin a supplementation for 2 months. Brain Res Bull 86:246–253.  https://doi.org/10.1016/j.brainresbull.2011.08.006 CrossRefGoogle Scholar
  13. de Oliveira MR, Ferreira GC, Schuck PF, Dal Bosco SM (2015) Role for the PI3K/Akt/Nrf2 signaling pathway in the protective effects of carnosic acid against methylglyoxal-induced neurotoxicity in SH-SY5Y neuroblastoma cells. Chem Biol Interact 242:396–406.  https://doi.org/10.1016/j.cbi.2015.11.003 CrossRefGoogle Scholar
  14. de Oliveira MR, Peres A, Ferreira GC, Schuck PF, Bosco SM (2016) Carnosic acid affords mitochondrial protection in Chlorpyrifos-treated Sh-Sy5y cells. Neurotox Res 30:367–379.  https://doi.org/10.1007/s12640-016-9620-x CrossRefGoogle Scholar
  15. de Oliveira MR, Brasil FB, Andrade CMB (2017a) Naringenin attenuates H2O2-induced mitochondrial dysfunction by an Nrf2-dependent mechanism in SH-SY5Y cells. Neurochem Res 42:3341–3350.  https://doi.org/10.1007/s11064-017-2376-8 CrossRefGoogle Scholar
  16. de Oliveira MR, Schuck PF, Bosco SMD (2017b) Tanshinone I induces mitochondrial protection through an Nrf2-dependent mechanism in Paraquat-TreatedHuman neuroblastoma SH-SY5Y cells. Mol Neurobiol 54:4597–4608.  https://doi.org/10.1007/s12035-016-0009-x CrossRefGoogle Scholar
  17. de Oliveira MR, da Costa FG, Brasil FB, Peres A (2018a) Pinocembrin suppresses H2O2-induced mitochondrial dysfunction by a mechanism dependent on the Nrf2/HO-1 Axis in SH-SY5Y cells. Mol Neurobiol 55:989–1003.  https://doi.org/10.1007/s12035-016-0380-7 CrossRefGoogle Scholar
  18. de Oliveira MR, de Souza ICC, Fürstenau CR (2018b) Carnosic acid induces anti-inflammatory effects in Paraquat-treated SH-SY5Y cells through a mechanism involving a crosstalk between the Nrf2/HO-1 Axis and NF-κB. Mol Neurobiol 55:890–897.  https://doi.org/10.1007/s12035-017-0389-6 CrossRefGoogle Scholar
  19. de Oliveira MR, Andrade CMB, Fürstenau CR (2018c) Naringenin exerts anti-inflammatory effects in Paraquat-treated SH-SY5Y cells through a mechanism associated with the Nrf2/HO-1 Axis. Neurochem Res 43:894–903.  https://doi.org/10.1007/s11064-018-2495-x CrossRefGoogle Scholar
  20. de Oliveira MR, da Costa FG, Peres A, Bosco SMD (2018d) Carnosic acid suppresses the H2O2-induced mitochondria-related bioenergetics disturbances and redox impairment in SH-SY5Y cells: role for Nrf2. Mol Neurobiol 55:968–979.  https://doi.org/10.1007/s12035-016-0372-7 CrossRefGoogle Scholar
  21. de Oliveira MR, Brasil FB, Fürstenau CR (2018e) Evaluation of the mitochondria-related redox and bioenergetics effects of Gastrodin in SH-SY5Y cells exposed to hydrogen peroxide. J Mol Neurosci 64:242–251.  https://doi.org/10.1007/s12031-018-1027-0 CrossRefGoogle Scholar
  22. de Oliveira MR, de Bittencourt BF, Fürstenau CR (2019a) Inhibition of the Nrf2/HO-1 Axis suppresses the mitochondria-related protection promoted by Gastrodin in human neuroblastoma cells exposed to Paraquat. Mol Neurobiol 56:2174–2184.  https://doi.org/10.1007/s12035-018-1222-6 CrossRefGoogle Scholar
  23. de Oliveira MR, Duarte AR, Chenet AL, de Almeida FJS, Andrade CMB (2019b) Carnosic acid pretreatment attenuates mitochondrial dysfunction in SH-SY5Y cells in an experimental model of glutamate-induced excitotoxicity. Neurotox Res IN PRESS doi.  https://doi.org/10.1007/s12640-019-00044-8
  24. Di Loreto S, Zimmitti V, Sebastiani P, Cervelli C, Falone S, Amicarelli F (2008) Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons. Int J Biochem Cell Biol 40:245–257CrossRefGoogle Scholar
  25. Dinkova-Kostova AT, Abramov AY (2015) The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med 88:179–188.  https://doi.org/10.1016/j.freeradbiomed.2015.04.036 CrossRefGoogle Scholar
  26. Dröse S, Brandt U (2008) The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex. J Biol Chem 283:21649–21654.  https://doi.org/10.1074/jbc.M803236200 CrossRefGoogle Scholar
  27. Dröse S, Brandt U (2012) Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Adv Exp Med Biol 748:145–169.  https://doi.org/10.1007/978-1-4614-3573-0_6 CrossRefGoogle Scholar
  28. Friedman JR, Nunnari J (2014) Mitochondrial form and function. Nature 505:335–343.  https://doi.org/10.1038/nature12985 CrossRefGoogle Scholar
  29. Fukuma Y, Sakai E, Nishishita K, Okamoto K, Tsukuba T (2015) Cafestol has a weaker inhibitory effect on osteoclastogenesis than kahweol and promotes osteoblast differentiation. Biofactors 41:222–231.  https://doi.org/10.1002/biof.1218 CrossRefGoogle Scholar
  30. Guix FX, Ill-Raga G, Bravo R, Nakaya T, de Fabritiis G, Coma M, Miscione GP, Villà-Freixa J, Suzuki T, Fernàndez-Busquets X, Valverde MA, de Strooper B, Muñoz FJ (2009) Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation. Brain 132:1335–1345.  https://doi.org/10.1093/brain/awp023 CrossRefGoogle Scholar
  31. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658.  https://doi.org/10.1111/j.1471-4159.2006.03907.x CrossRefGoogle Scholar
  32. Holmström KM, Kostov RV, Dinkova-Kostova AT (2016) The multifaceted role of Nrf2 in mitochondrial function. Curr Opin Toxicol 1:80–91.  https://doi.org/10.1016/j.cotox.2016.10.002 CrossRefGoogle Scholar
  33. Hwang YP, Jeong HG (2008) The coffee diterpene kahweol induces heme oxygenase-1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress. FEBS Lett 582:2655–2662.  https://doi.org/10.1016/j.febslet.2008.06.045 CrossRefGoogle Scholar
  34. Jodeiri Farshbaf M, Ghaedi K (2017) Huntington's disease and mitochondria. Neurotox Res 32:518–529.  https://doi.org/10.1007/s12640-017-9766-1 CrossRefGoogle Scholar
  35. Kalapos MP (2008) The tandem of free radicals and methylglyoxal. Chem Biol Interact 171:251–271.  https://doi.org/10.1016/j.cbi.2007.11.009 CrossRefGoogle Scholar
  36. Lacza Z, Kozlov AV, Pankotai E, Csordás A, Wolf G, Redl H, Kollai M, Szabó C, Busija DW, Horn TF (2006) Mitochondria produce reactive nitrogen species via an arginine-independent pathway. Free Radic Res 40:369–378CrossRefGoogle Scholar
  37. LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231CrossRefGoogle Scholar
  38. Lee KJ, Jeong HG (2007) Protective effects of kahweol and cafestol against hydrogen peroxide-induced oxidative stress and DNA damage. Toxicol Lett 173:80–87CrossRefGoogle Scholar
  39. Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830:3143–3153.  https://doi.org/10.1016/j.bbagen.2012.09.008 CrossRefGoogle Scholar
  40. Lushchak VI (2014) Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact 224:164–175.  https://doi.org/10.1016/j.cbi.2014.10.016 CrossRefGoogle Scholar
  41. Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426.  https://doi.org/10.1146/annurev-pharmtox-011112-140320 CrossRefGoogle Scholar
  42. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRefGoogle Scholar
  43. Nemet I, Varga-Defterdarović L, Turk Z (2006) Methylglyoxal in food and living organisms. Mol Nutr Food Res 50:1105–1117CrossRefGoogle Scholar
  44. Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284:13291–13295.  https://doi.org/10.1074/jbc.R900010200 CrossRefGoogle Scholar
  45. Nishimoto S, Koike S, Inoue N, Suzuki T, Ogasawara Y (2017) Activation of Nrf2 attenuates carbonyl stress induced by methylglyoxal in human neuroblastoma cells: increase in GSH levels is a critical event for the detoxification mechanism. Biochem Biophys Res Commun 483:874–879.  https://doi.org/10.1016/j.bbrc.2017.01.024 CrossRefGoogle Scholar
  46. Ochoa JJ, Pamplona R, Ramirez-Tortosa MC, Granados-Principal S, Perez-Lopez P, Naudí A, Portero-Otin M, López-Frías M, Battino M, Quiles JL (2011) Age-related changes in brain mitochondrial DNA deletion and oxidative stress are differentially modulated by dietary fat type and coenzyme Q10. Free Radic Biol Med 50:1053–1064.  https://doi.org/10.1016/j.freeradbiomed.2011.02.004 CrossRefGoogle Scholar
  47. Papa S, Martino PL, Capitanio G, Gaballo A, De Rasmo D, Signorile A, Petruzzella V (2012) The oxidative phosphorylation system in mammalian mitochondria. Adv Exp Med Biol 942:3–37.  https://doi.org/10.1007/978-94-007-2869-1_1 CrossRefGoogle Scholar
  48. Poderoso JJ, Carreras MC, Lisdero C, Riobó N, Schöpfer F, Boveris A (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328:85–92CrossRefGoogle Scholar
  49. Pun PB, Murphy MP (2012) Pathological significance of mitochondrial glycation. Int J Cell Biol 2012:843505–843513.  https://doi.org/10.1155/2012/843505 CrossRefGoogle Scholar
  50. Richard JP (1993) Mechanism for the formation of methylglyoxal from triosephosphates. Biochem Soc Trans 21:549–553CrossRefGoogle Scholar
  51. Rosca MG, Mustata TG, Kinter MT, Ozdemir AM, Kern TS, Szweda LI, Brownlee M, Monnier VM, Weiss MF (2005) Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Ren Physiol 289:F420–F430CrossRefGoogle Scholar
  52. Rowan S, Bejarano E, Taylor A (2018) Mechanistic targeting of advanced glycation end-products in age-related diseases. Biochim Biophys Acta Mol basis Dis 1864:3631–3643.  https://doi.org/10.1016/j.bbadis.2018.08.036 CrossRefGoogle Scholar
  53. Sies H, Berndt C, Jones DP (2017) Oxidative stress. Annu Rev Biochem 86:715–748.  https://doi.org/10.1146/annurev-biochem-061516-045037 CrossRefGoogle Scholar
  54. Thornalley PJ (2003) Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 31:1343–1348CrossRefGoogle Scholar
  55. Thornalley PJ (2005) Dicarbonyl intermediates in the maillard reaction. Ann N Y Acad Sci 1043:111–117.  https://doi.org/10.1196/annals.1333.014 CrossRefGoogle Scholar
  56. Thorpe SR, Baynes JW (2003) Maillard reaction products in tissue proteins: new products and new perspectives. Amino Acids 25:275–281CrossRefGoogle Scholar
  57. Wang K, Zhu L, Zhu X, Zhang K, Huang B, Zhang J, Zhang Y, Zhu L, Zhou B, Zhou F (2014) Protective effect of paeoniflorin on Aβ25-35-induced SH-SY5Y cell injury by preventing mitochondrial dysfunction. Cell Mol Neurobiol 34:227–234.  https://doi.org/10.1007/s10571-013-0006-9 CrossRefGoogle Scholar
  58. Weidinger A, Kozlov AV (2015) Biological activities of reactive oxygen and nitrogen species: oxidative stress versus signal transduction. Biomolecules 5:472–484.  https://doi.org/10.3390/biom5020472 CrossRefGoogle Scholar
  59. Wu KC, McDonald PR, Liu J, Klaassen CD (2014) Screening of natural compounds as activators of the keap1-nrf2 pathway. Planta Med 80:97–104.  https://doi.org/10.1055/s-0033-1351097 Google Scholar
  60. Zhang L, Wang H (2018) Targeting the NF-E2-related factor 2 pathway: a novel strategy for traumatic brain injury. Mol Neurobiol 55:1773–1785.  https://doi.org/10.1007/s12035-017-0456-z CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas BioativasUniversidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  2. 2.Programa de Pós-Graduação em Química (PPGQ)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  3. 3.Programa de Pós-Graduação em Ciências da Saúde (PPGCS)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  4. 4.Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBIO), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Instituto de BiologiaUniversidade Federal de Pelotas (UFPel)PelotasBrazil
  5. 5.Centro de Ciências Naturais e HumanasUniversidade Federal do ABCSanto AndréBrazil

Personalised recommendations