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Carnosic Acid Suppresses the H2O2-Induced Mitochondria-Related Bioenergetics Disturbances and Redox Impairment in SH-SY5Y Cells: Role for Nrf2

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Abstract

The phenolic diterpene carnosic acid (CA, C20H28O4) exerts antioxidant, anti-inflammatory, anti-apoptotic, and anti-cancer effects in mammalian cells. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2), among other signaling pathways, and restores cell viability in several in vitro and in vivo experimental models. We have previously reported that CA affords mitochondrial protection against various chemical challenges. However, it was not clear yet whether CA would prevent chemically induced impairment of the tricarboxylic acid cycle (TCA) function in mammalian cells. In the present work, we found that a pretreatment of human neuroblastoma SH-SY5Y cells with CA at 1 μM for 12 h prevented the hydrogen peroxide (H2O2)-induced impairment of the TCA enzymes (aconitase, α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH)) and abolished the inhibition of the complexes I and V and restored the levels of ATP by a mechanism associated with Nrf2. CA also exhibited antioxidant abilities by enhancing the levels of reduced glutathione (GSH) and decreasing the content oxidative stress markers (cellular 8-oxo-2′-deoxyguanosine (8-oxo-dG), and mitochondrial malondialdehyde (MDA), protein carbonyl, and 3-nitrotyrosine). Silencing of Nrf2 by small interfering RNA (siRNA) abrogated the protective effects elicited by CA in mitochondria of SH-SY5Y cells. Therefore, CA prevented the H2O2-triggered mitochondrial impairment by an Nrf2-dependent mechanism. The specific role of Nrf2 in ameliorating the function of TCA enzymes function needs further research.

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References

  1. Lushchak VI (2014) Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact 224:164–175. doi:10.1016/j.cbi.2014.10.016

    Article  CAS  PubMed  Google Scholar 

  2. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. doi:10.1042/BJ20081386

    Article  CAS  PubMed  Google Scholar 

  3. Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30:11–26. doi:10.1007/s12291-014-0446-0

    Article  CAS  PubMed  Google Scholar 

  4. Bornhövd C, Vogel F, Neupert W, Reichert AS (2006) Mitochondrial membrane potential is dependent on the oligomeric state of F1F0-ATP synthase supracomplexes. J Biol Chem 281:13990–13998

    Article  PubMed  Google Scholar 

  5. McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560

    Article  CAS  PubMed  Google Scholar 

  6. Butler J, Jayson GG, Swallow AJ (1975) The reaction between the superoxide anion radical and cytochrome c. Biochim Biophys Acta 408:215–222

    Article  CAS  PubMed  Google Scholar 

  7. Cadenas E, Boveris A, Ragan CI, Stoppani AO (1977) Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Arch Biochem Biophys 180:248–257

    Article  CAS  PubMed  Google Scholar 

  8. Beyer RE (1990) The participation of coenzyme Q in free radical production and antioxidation. Free Radic Biol Med 8:545–565

    Article  CAS  PubMed  Google Scholar 

  9. Barja G (1999) Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr 31:347–366

    Article  CAS  PubMed  Google Scholar 

  10. Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD (2010) Mitochondrial proton and electron leaks. Essays Biochem 47:53–67. doi:10.1042/bse0470053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li C, Zhou HM (2011) The role of manganese superoxide dismutase in inflammation defense. Enzyme Res 2011:387176. doi:10.4061/2011/387176

    PubMed  PubMed Central  Google Scholar 

  13. Bakthavatchalu V, Dey S, Xu Y, Noel T, Jungsuwadee P, Holley AK, Dhar SK, Batinic-Haberle I et al (2012) Manganese superoxide dismutase is a mitochondrial fidelity protein that protects Polγ against UV-induced inactivation. Oncogene 31:2129–2139. doi:10.1038/onc.2011.407

    Article  CAS  PubMed  Google Scholar 

  14. Candas D, Li JJ (2014) MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antioxid Redox Signal 20:1599–1617. doi:10.1089/ars.2013.5305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. de Oliveira MR, Nabavi SF, Habtemariam S, Erdogan Orhan I, Daglia M, Nabavi SM (2015) The effects of baicalein and baicalin on mitochondrial function and dynamics: a review. Pharmacol Res 100:296–308. doi:10.1016/j.phrs.2015.08.021

    Article  PubMed  Google Scholar 

  16. Paravicini TM, Drummond GR, Sobey CG (2004) Reactive oxygen species in the cerebral circulation: physiological roles and therapeutic implications for hypertension and stroke. Drugs 64:2143–2157

    Article  CAS  PubMed  Google Scholar 

  17. Kamsler A, Segal M (2004) Hydrogen peroxide as a diffusible signal molecule in synaptic plasticity. Mol Neurobiol 29:167–178

    Article  CAS  PubMed  Google Scholar 

  18. Waghray M, Cui Z, Horowitz JC, Subramanian IM, Martinez FJ, Toews GB, Thannickal VJ (2005) Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts. FASEB J 19:854–856

    Article  CAS  PubMed  Google Scholar 

  19. Gough DR, Cotter TG (2011) Hydrogen peroxide: a Jekyll and Hyde signalling molecule. Cell Death Dis 2:e213. doi:10.1038/cddis.2011.96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658

    Article  CAS  PubMed  Google Scholar 

  21. Deponte M (2013) Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 1830:3217–3266. doi:10.1016/j.bbagen.2012.09.018

    Article  CAS  PubMed  Google Scholar 

  22. Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830:3143–3153. doi:10.1016/j.bbagen.2012.09.008

    Article  CAS  PubMed  Google Scholar 

  23. Atamna H, Mackey J, Dhahbi JM (2012) Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction. Biofactors 38:158–166. doi:10.1002/biof.197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gruber J, Fong S, Chen CB, Yoong S, Pastorin G, Schaffer S, Cheah I, Halliwell B (2013) Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing. Biotechnol Adv 31:563–592. doi:10.1016/j.biotechadv.2012.09.005

    Article  CAS  PubMed  Google Scholar 

  25. de Oliveira MR (2016) Evidence for genistein as a mitochondriotropic molecule. Mitochondrion 29:35–44. doi:10.1016/j.mito.2016.05.005

    Article  PubMed  Google Scholar 

  26. de Oliveira MR, Jardim FR, Setzer WN, Nabavi SM, Nabavi SF (2016) Curcumin, mitochondrial biogenesis, and mitophagy: exploring recent data and indicating future needs. Biotechnol Adv 34:813–826. doi:10.1016/j.biotechadv.2016.04.004

    Article  PubMed  Google Scholar 

  27. de Oliveira MR, Nabavi SF, Manayi A, Daglia M, Hajheydari Z, Nabavi SM (2016) Resveratrol and the mitochondria: from triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view. Biochim Biophys Acta 1860:727–745. doi:10.1016/j.bbagen.2016.01.017

    Article  PubMed  Google Scholar 

  28. de Oliveira MR, Nabavi SM, Braidy N, Setzer WN, Ahmed T, Nabavi SF (2016) Quercetin and the mitochondria: a mechanistic view. Biotechnol Adv 34:532–549. doi:10.1016/j.biotechadv.2015.12.014

    Article  PubMed  Google Scholar 

  29. Oliveira MR, Nabavi SF, Daglia M, Rastrelli L, Nabavi SM (2016) Epigallocatechin gallate and mitochondria—a story of life and death. Pharmacol Res 104:70–85. doi:10.1016/j.phrs.2015.12.027

    Article  CAS  PubMed  Google Scholar 

  30. Wiernsperger NF (2003) Oxidative stress: the special case of diabetes. Biofactors 19:11–18

    Article  CAS  PubMed  Google Scholar 

  31. Pérez-Neri I, Ramírez-Bermúdez J, Montes S, Ríos C (2006) Possible mechanisms of neurodegeneration in schizophrenia. Neurochem Res 31:1279–1294

    Article  PubMed  Google Scholar 

  32. Mc Guire PJ, Parikh A, Diaz GA (2009) Profiling of oxidative stress in patients with inborn errors of metabolism. Mol Genet Metab 98:173–180. doi:10.1016/j.ymgme.2009.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nunomura A, Moreira PI, Castellani RJ, Lee HG, Zhu X, Smith MA, Perry G (2012) Oxidative damage to RNA in aging and neurodegenerative disorders. Neurotox Res 22:231–248. doi:10.1007/s12640-012-9331-x

    Article  CAS  PubMed  Google Scholar 

  34. 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. doi:10.1007/s12035-013-8554-z

    Article  CAS  PubMed  Google Scholar 

  35. Kasote DM, Hegde MV, Katyare SS (2013) Mitochondrial dysfunction in psychiatric and neurological diseases: cause(s), consequence(s), and implications of antioxidant therapy. Biofactors 39:392–406. doi:10.1002/biof.1093

    Article  CAS  PubMed  Google Scholar 

  36. de Oliveira MR (2015) Vitamin A and retinoids as mitochondrial toxicants. Oxidative Med Cell Longev 2015:140267. doi:10.1155/2015/140267

    Article  Google Scholar 

  37. 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. doi:10.1016/j.neuint.2015.12.006

    Article  PubMed  Google Scholar 

  38. Foresti R, Bains SK, Pitchumony TS, de Castro Brás LE, Drago F, Dubois-Randé JL, Bucolo C, Motterlini R (2013) Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells. Pharmacol Res 76:132–148. doi:10.1016/j.phrs.2013.07.010

    Article  CAS  PubMed  Google Scholar 

  39. de Oliveira MR (2015) The dietary components carnosic acid and carnosol as neuroprotective agents: a mechanistic view. Mol Neurobiol IN PRESS doi. doi:10.1007/s12035-015-9519-1

    Google Scholar 

  40. Wu CR, Tsai CW, Chang SW, Lin CY, Huang LC, Tsai CW (2015) Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson’s disease: involvement of antioxidative enzymes induction. Chem Biol Interact 225:40–46. doi:10.1016/j.cbi.2014.11.011

    Article  CAS  PubMed  Google Scholar 

  41. Chen SD, Ji BB, Yan YX, He X, Han KY, Dai QX, Zhang MX, Mo YC et al (2016) Carnosic acid attenuates neuropathic pain in rat through the activation of spinal sirtuin1 and down-regulation of p66shc expression. Neurochem Int 93:95–102. doi:10.1016/j.neuint.2016.01.004

    Article  PubMed  Google Scholar 

  42. Jung KJ, Min KJ, Park JW, Park KM, Kwon TK (2016) Carnosic acid attenuates unilateral ureteral obstruction-induced kidney fibrosis via inhibition of Akt-mediated Nox4 expression. Free Radic Biol Med 97:50–57. doi:10.1016/j.freeradbiomed.2016.05.020

    Article  CAS  PubMed  Google Scholar 

  43. Su K, Wang CF, Zhang Y, Cai YJ, Zhang YY, Zhao Q (2016) The inhibitory effects of carnosic acid on cervical cancer cells growth by promoting apoptosis via ROS-regulated signaling pathway. Biomed Pharmacother 82:180–191. doi:10.1016/j.biopha.2016.04.056

    Article  CAS  PubMed  Google Scholar 

  44. Tian X, Hu Y, Li M, Xia K, Yin J, Chen J, Liu Z (2016) Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway. Can J Physiol Pharmacol 94:416–425. doi:10.1139/cjpp-2015-0276

    Article  CAS  PubMed  Google Scholar 

  45. Kapoor S (2013) Carnosic acid and its inhibitory effect on tumor growth in systemic malignancies. Oral Dis 19:427. doi:10.1111/odi.12055

    Article  PubMed  Google Scholar 

  46. Gao Q, Liu H, Yao Y, Geng L, Zhang X, Jiang L, Shi B, Yang F (2015) Carnosic acid induces autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells. J Appl Toxicol 35:485–492. doi:10.1002/jat.3049

    Article  CAS  PubMed  Google Scholar 

  47. Hao L, Ran W, Xiang-Xin L, Lu-Qun W, Xiao-Ning Y (2016) Carnosic acid-combined arsenic trioxide antileukaemia cells in the establishment of NB4/SCID mouse model. Basic Clin Pharmacol Toxicol 119:259–266. doi:10.1111/bcpt.12580

    Article  PubMed  Google Scholar 

  48. 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. doi:10.1016/j.cbi.2015.11.003

    Article  PubMed  Google Scholar 

  49. de Oliveira MR, Ferreira GC, Schuck PF (2016) Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: role for PI3K/Akt/Nrf2 pathway. Toxicol in Vitro 32:41–54. doi:10.1016/j.tiv.2015.12.005

    Article  PubMed  Google Scholar 

  50. 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 IN PRESS doi. doi:10.1007/s12640-016-9620-x

    Google Scholar 

  51. Satoh T, Kosaka K, Itoh K, Kobayashi A, Yamamoto M, Shimojo Y, Kitajima C, Cui J et al (2008) Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem 104:1116–1131

    Article  CAS  PubMed  Google Scholar 

  52. Vaka SR, Shivakumar HN, Repka MA, Murthy SN (2013) Formulation and evaluation of carnosic acid nanoparticulate system for upregulation of neurotrophins in the brain upon intranasal administration. J Drug Target 21:44–53. doi:10.3109/1061186X.2012.725405

    Article  CAS  PubMed  Google Scholar 

  53. Meng P, Yoshida H, Tanji K, Matsumiya T, Xing F, Hayakari R, Wang L, Tsuruga K et al (2015) Carnosic acid attenuates apoptosis induced by amyloid-β 1-42 or 1-43 in SH-SY5Y human neuroblastoma cells. Neurosci Res 94:1–9. doi:10.1016/j.neures.2014.12.003

    Article  CAS  PubMed  Google Scholar 

  54. Miller DM, Singh IN, Wang JA, Hall ED (2015) Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice. Exp Neurol 264:103–110. doi:10.1016/j.expneurol.2014.11.008

    Article  CAS  PubMed  Google Scholar 

  55. Zhang D, Lee B, Nutter A, Song P, Dolatabadi N, Parker J, Sanz-Blasco S, Newmeyer T et al (2015) Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid. J Neurochem 133:898–908. doi:10.1111/jnc.13074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  57. de Oliveira MR, Schuck PF, Bosco SM (2016) Tanshinone I induces mitochondrial protection through an Nrf2-dependent mechanism in paraquat-treated human neuroblastoma SH-SY5Y cells. Mol Neurobiol IN PRESS. doi:10.1007/s12035-016-0009-x

    Google Scholar 

  58. 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 5:227–231

    Article  CAS  PubMed  Google Scholar 

  59. De Oliveira MR, Oliveira MW, Da Rocha RF, Moreira JC (2009) Vitamin A supplementation at pharmacological doses induces nitrosative stress on the hypothalamus of adult Wistar rats. Chem Biol Interact 180:407–413. doi:10.1016/j.cbi.2009.02.006

    Article  PubMed  Google Scholar 

  60. 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. doi:10.1016/j.brainresbull.2011.08.006

    Article  PubMed  Google Scholar 

  61. de Oliveira MR, da Rocha RF, Moreira JC (2012) Increased susceptibility of mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats to non-aggregated amyloid-β peptides 1-40 and 1-42. Acta Neuropsychiatr 24:101–108. doi:10.1111/j.1601-5215.2011.00588.x

    Article  PubMed  Google Scholar 

  62. de Oliveira MR, da Rocha RF, Schnorr CE, Moreira JC (2012) L-NAME cotreatment did prevent neither mitochondrial impairment nor behavioral abnormalities in adult Wistar rats treated with vitamin A supplementation. Fundam Clin Pharmacol 26:513–529. doi:10.1111/j.1472-8206.2011.00943.x

    Article  PubMed  Google Scholar 

  63. Wang K, Zhu L, Zhu X, Zhang K, Huang B, Zhang J, Zhang Y, Zhu L et al (2014) Protective effect of paeoniflorin on Aβ25-35-induced SH-SY5Y cell injury by preventing mitochondrial dysfunction. Cell Mol Neurobiol 34:227–234. doi:10.1007/s10571-013-0006-9

    Article  PubMed  Google Scholar 

  64. 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 328:85–92

    Article  CAS  PubMed  Google Scholar 

  65. de Oliveira MR, da Rocha RF, Stertz L, Fries GR, de Oliveira DL, Kapczinski F, Moreira JC (2011) Total and mitochondrial nitrosative stress, decreased brain-derived neurotrophic factor (BDNF) levels and glutamate uptake, and evidence of endoplasmic reticulum stress in the hippocampus of vitamin A-treated rats. Neurochem Res 36:506–517. doi:10.1007/s11064-010-0372-3

    Article  PubMed  Google Scholar 

  66. Quesada A, Ogi J, Schultz J, Handforth A (2011) C-terminal mechano-growth factor induces heme oxygenase-1-mediated neuroprotection of SH-SY5Y cells via the protein kinase Cϵ/Nrf2 pathway. J Neurosci Res 89:394–405. doi:10.1002/jnr.22543

    Article  CAS  PubMed  Google Scholar 

  67. Jin X, Liu Q, Jia L, Li M, Wang X (2015) Pinocembrin attenuates 6-OHDA-induced neuronal cell death through Nrf2/ARE pathway in SH-SY5Y cells. Cell Mol Neurobiol 35:323–333. doi:10.1007/s10571-014-0128-8

    Article  CAS  PubMed  Google Scholar 

  68. D’Autréaux, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    Article  PubMed  Google Scholar 

  69. Chinopoulos C, Tretter L, Adam-Vizi V (1999) Depolarization of in situ mitochondria due to hydrogen peroxide-induced oxidative stress in nerve terminals: inhibition of alpha-ketoglutarate dehydrogenase. J Neurochem 73:220–228

    Article  CAS  PubMed  Google Scholar 

  70. Nulton-Persson AC, Szweda LI (2001) Modulation of mitochondrial function by hydrogen peroxide. J Biol Chem 276:23357–23361. doi:10.1074/jbc.M100320200

    Article  CAS  PubMed  Google Scholar 

  71. Chernyak BV, Bernardi P (1996) The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur J Biochem 238:623–630

    Article  CAS  PubMed  Google Scholar 

  72. Costantini P, Chernyak BV, Petronilli V, Bernardi P (1996) Modulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites. J Biol Chem 271:6746–6751

    Article  CAS  PubMed  Google Scholar 

  73. Chernyak BV (1997) Redox regulation of the mitochondrial permeability transition pore. Biosci Rep 17:293–302

    Article  CAS  PubMed  Google Scholar 

  74. Lieven CJ, Vrabec JP, Levin LA (2003) The effects of oxidative stress on mitochondrial transmembrane potential in retinal ganglion cells. Antioxid Redox Signal 5:641–646

    Article  CAS  PubMed  Google Scholar 

  75. Fato R, Bergamini C, Leoni S, Lenaz G (2008) Mitochondrial production of reactive oxygen species: role of complex I and quinone analogues. Biofactors 32:31–39

    Article  CAS  PubMed  Google Scholar 

  76. Wang CH, Wu SB, Wu YT, Wei YH (2013) Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Exp Biol Med (Maywood) 238:450–460. doi:10.1177/1535370213493069

    Article  Google Scholar 

  77. Schinder AF, Olson EC, Spitzer NC, Montal M (1996) Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J Neurosci 16:6125–6133

    CAS  PubMed  Google Scholar 

  78. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  CAS  PubMed  Google Scholar 

  79. Deschepper M, Hoogendoorn B, Brooks S, Dunnett SB, Jones L (2012) Proteomic changes in the brains of Huntington’s disease mouse models reflect pathology and implicate mitochondrial changes. Brain Res Bull 88:210–222. doi:10.1016/j.brainresbull.2011.01.012

    Article  CAS  PubMed  Google Scholar 

  80. Lezi E, Swerdlow RH (2012) Mitochondria in neurodegeneration. Adv Exp Med Biol 942:269–286. doi:10.1007/978-94-007-2869-1_12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. de Oliveira MR (2016) Fluoxetine and the mitochondria: a review of the toxicological aspects. Toxicol Lett 258:185–191. doi:10.1016/j.toxlet.2016.07.001

    Article  PubMed  Google Scholar 

  82. Fernández-Checa JC, Kaplowitz N, García-Ruiz C, Colell A, Miranda M, Marí M, Ardite E, Morales A (1997) GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Phys 273:G7–G17

    Article  Google Scholar 

  83. García-Ruiz C, Colell A, Marí M, Morales A, Fernández-Checa JC (1997) Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione J Biol Chem 272:11369–11377

    PubMed  Google Scholar 

  84. Fernández-Checa JC, García-Ruiz C, Colell A, Morales A, Marí M, Miranda M, Ardite E (1998) Oxidative stress: role of mitochondria and protection by glutathione. Biofactors 8:7–11

    Article  PubMed  Google Scholar 

  85. Tretter L, Adam-Vizi V (2000) Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci 20:8972–8979

    CAS  PubMed  Google Scholar 

  86. Kil IS, Park JW (2005) Regulation of mitochondrial NADP+-dependent isocitrate dehydrogenase activity by glutathionylation. J Biol Chem 280:10846–10854

    Article  CAS  PubMed  Google Scholar 

  87. Hattori N, Tanaka M, Ozawa T, Mizuno Y (1991) Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson’s disease. Ann Neurol 30:563–571

    Article  CAS  PubMed  Google Scholar 

  88. Kingsbury AE, Cooper M, Schapira AH, Foster OJ (2001) Metabolic enzyme expression in dopaminergic neurons in Parkinson’s disease: an in situ hybridization study. Ann Neurol 50:142–149

    Article  CAS  PubMed  Google Scholar 

  89. Gibson GE, Kingsbury AE, Xu H, Lindsay JG, Daniel S, Foster OJ, Lees AJ, Blass JP (2003) Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson’s disease. Neurochem Int 43:129–135

    Article  CAS  PubMed  Google Scholar 

  90. Mastrogiacomo F, Bergeron C, Kish SJ (1993) Brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer’s disease. J Neurochem 61:2007–2014

    Article  CAS  PubMed  Google Scholar 

  91. Sheu KF, Cooper AJ, Koike K, Koike M, Lindsay JG, Blass JP (1994) Abnormality of the alpha-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer’s disease. Ann Neurol 35:312–318

    Article  CAS  PubMed  Google Scholar 

  92. Browne SE, Beal MF (2004) The energetics of Huntington’s disease. Neurochem Res 29:531–546

    Article  CAS  PubMed  Google Scholar 

  93. Armstrong JS (2007) Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br J Pharmacol 151:1154–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Heller A, Brockhoff G, Goepferich A (2012) Targeting drugs to mitochondria. Eur J Pharm Biopharm 82:1–18. doi:10.1016/j.ejpb.2012.05.014

    Article  CAS  PubMed  Google Scholar 

  95. Hayes JD, Dinkova-Kostova AT (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39:199–218. doi:10.1016/j.tibs.2014.02.002

    Article  CAS  PubMed  Google Scholar 

  96. Ludtmann MH, Angelova PR, Zhang Y, Abramov AY, Dinkova-Kostova AT (2014) Nrf2 affects the efficiency of mitochondrial fatty acid oxidation. Biochem J 457:415–424. doi:10.1042/BJ20130863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kim TH, Hur EG, Kang SJ, Kim JA, Thapa D, Lee YM, Ku SK, Jung Y et al (2011) NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1α. Cancer Res 71:2260–2275. doi:10.1158/0008-5472.CAN-10-3007

    Article  CAS  PubMed  Google Scholar 

  98. Cornejo P, Vargas R, Videla LA (2013) Nrf2-regulated phase-II detoxification enzymes and phase-III transporters are induced by thyroid hormone in rat liver. Biofactors 39:514–521. doi:10.1002/biof.1094

    Article  CAS  PubMed  Google Scholar 

  99. Lin CY, Chen JH, Fu RH, Tsai CW (2014) Induction of Pi form of glutathione S-transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity. Chem Res Toxicol 27:1958–1966. doi:10.1021/tx5003063

    Article  CAS  PubMed  Google Scholar 

  100. Rohlenova K, Neuzil J, Rohlena J (2016) The role of Her2 and other oncogenes of the PI3K/AKT pathway in mitochondria. Biol Chem 397:607–615. doi:10.1515/hsz-2016-0130

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

GCF is supported by Edital APQ1/FAPERJ and receives a “Produtividade em Pesquisa do CNPq - Nível 2” fellow. This work was supported by CNPq.

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  1. Departamento de Química/ICET, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa , 2367 , Cuiaba, MT, 78060-900, Brazil

    Marcos Roberto de Oliveira

  2. Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Gustavo da Costa Ferreira

  3. Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Alessandra Peres

  4. Centro de Pesquisa da Pós-Graduação, Centro Universitário Metodista IPA, Porto Alegre, RS, Brazil

    Alessandra Peres

  5. Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Simone Morelo Dal Bosco

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  1. Marcos Roberto de Oliveira
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  2. Gustavo da Costa Ferreira
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  3. Alessandra Peres
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  4. Simone Morelo Dal Bosco
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Correspondence to Marcos Roberto de Oliveira.

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de Oliveira, M.R., da Costa Ferreira, G., Peres, A. et al. 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 (2018). https://doi.org/10.1007/s12035-016-0372-7

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  • DOI: https://doi.org/10.1007/s12035-016-0372-7

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