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Oxidative Stress, Redox Homeostasis and Cellular Stress Response in Ménière’s Disease: Role of Vitagenes

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Abstract

Ménière’s disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on post-mortem examination. Increasing evidence suggests that oxidative stress is involved in the development of endolymphatic hydrops and that cellular damage and apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of MD. While excess reactive oxygen species (ROS) are toxic, regulated ROS, however, play an important role in cellular signaling. The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) as well as the thioredoxin/thioredoxin reductase system. In this study we tested the hypothesis that in MD patients measurable increases in markers of cellular stress response and oxidative stress in peripheral blood are present. This study also explores the hypothesis that changes in the redox status of glutathione, the major endogenous antioxidant, associated with abnormal expression and activity of carbonic anhydrase can contribute to increase oxidative stress and to disruption of systemic redox homeostasis which can be associated to possible alterations on vulnerable neurons such as spiral ganglion neurons and consequent cellular degeneration. We therefore evaluated systemic oxidative stress and cellular stress response in patients suffering from Meniere’s disease (MD) and in age-matched healthy subjects. Systemic oxidative stress was estimated by measuring protein oxidation, such as protein carbonyls (PC) and 4-hydroxynonenal (HNE) in lymphocytes of MD patients, as well as ultraweak luminescence (UCL) as end-stable products of lipid oxidation in MD plasma and lymphocytes, as compared to age-matched controls, whereas heat shock proteins Hsp70 and thioredoxin (Trx) expression were measured in lymphocytes to evaluate the systemic cellular stress response. Increased levels of PC (P < 0.01) and HNE (P < 0.05) have been found in lymphocytes from MD patients with respect to control group. This was paralleled by a significant induction of Hsp70, and a decreased expression of Trx (P < 0.01), whereas a significant decrease in both plasma and lymphocyte ratio reduced glutathione GSH) vs. oxidized glutathione (GSSG) (P < 0.05) were also observed. In conclusion, patients affected by MD are under condition of systemic oxidative stress and the induction of vitagenes Hsp70 is a maintained response in counteracting the intracellular pro-oxidant status generated by decreased content of GSH as well as expression of Trx. The search for novel and more potent inducers of vitagenes will facilitate the development of pharmacological strategies to increase the intrinsic capacity of vulnerable ganglion cells to maximize antidegenerative mechanisms, such as stress response and thus cytoprotection.

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References

  1. Yoo TJ, Du X, Kwon S (2002) Molecular mechanism of autoimmune hearing loss. Acta Otolaryngol Suppl 548:3–9

    Article  PubMed  Google Scholar 

  2. Melki SJ, Heddon CM, Frankel JK, Levitt AH, Momin SR, Alagramam KN, Megerian CA (2010) Pharmacological protection of hearing loss in the mouse model of endolymphatic hydrops. Laryngoscope 120:1637–1645

    Article  CAS  PubMed  Google Scholar 

  3. Megerian CA, Cliff A (2005) Diameter of the cochlear nerve in endolymphatic hydrops: implications for the etiology of hearing loss in Ménière’s disease. Laryngoscope 9:1525–1535

    Article  Google Scholar 

  4. Labbé D, Teranishia M, Hessa A, Blochb W, Michel O (2005) Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea. Hear Reearche 202:21–27

    Article  Google Scholar 

  5. Calabrese V, Guagliano E, Sapienza M, Panebianco M, Calafato S, Puleo E, Pennisi G, Mancuso C, Butterfield DA, Giuffrida AM (2007) Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of vitagenes. Neurochem Res 32:757–773

    Article  CAS  PubMed  Google Scholar 

  6. Calabrese V, Mancuso C, Ravagna A, Perluigi M, Cini C, De Marco C, Butterfield DA, Giuffrida A (2007) In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state. J Neurochem 10:709–717

    Article  Google Scholar 

  7. Calabrese V, Mancuso C, Sapienza M, Puleo E, Calafato S, Cornelius C, Finocchiaro M, Mangiameli A, Di Mauro M, Giuffrida A, Castellino P (2007) Oxidative stress, and cellular stress response in diabetic nephropathy. Cell Stress Chaperons 12:299–306

    Article  CAS  Google Scholar 

  8. Calabrese V, Signorile A, Cornelius C, Mancuso C, Scapagnini G, Ventimiglia B, Ragusa N, Dinkova-Kostova A (2008) Pratical approaches to investigate redox regulation of heat shock protein epression and intracellular glutathione redox state. Methods Enzymol 441:83–110

    Article  CAS  PubMed  Google Scholar 

  9. Nacci A, Dallan I, Monzani F, Dardano A, Migliorini P, Riente L, Ursino F, Fattori B (2009) Elevated antithyroid peroxidase and antinuclear autoantibody titers in Ménière’s disease patients: more than a chance association? Audiol Neurootol 15:1–6

    PubMed  Google Scholar 

  10. Bellia F, Calabrese V, Guarino F, Cavallaro M, Cornelius C, De Pinto V, Rizzarelli E (2009) Carnosinase levels in aging brain: redox state induction and cellular stress response. Antioxid Redox Signal 11:2759–2775

    Article  CAS  PubMed  Google Scholar 

  11. Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP (2010) Cellular stress responses, the hormesis paradigm and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal 610:285–308

    CAS  Google Scholar 

  12. Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ (2009) Vitagenes, cellular stress response and acetylcarnitine: relevance to hormesis. Biofactors 35:146–160

    Article  CAS  PubMed  Google Scholar 

  13. Abi-Hachem RN, Zine A, Van De Water TR (2010) The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies. Recent Pat CNS Drug Discov 5:147–163

    Article  CAS  PubMed  Google Scholar 

  14. Söderman AC, Bagger-Sjöbäck D, Bergenius J, Langius A (2002) A Factors influencing quality of life in patients with Ménière’s disease, identified by a multidimensional approach. Otol Neurotol 23:941–948

    Article  PubMed  Google Scholar 

  15. Semaan MT, Megerian CA (2010) Contemporary perspectives on the pathophysiology of Meniere’s disease: implications for treatment. Curr Opin Otolaryngol Head Neck Surg

  16. Best C, Eckhardt-Henn A, Tschan R, Dieterich M (2009) Psychiatric morbidity and comorbidity in different vestibular vertigo syndromes. Results of a prospective longitudinal study over 1 year. J Neurol 256:58–65

    Article  PubMed  Google Scholar 

  17. Brambilla D, Mancuso C, Scuderi MR, Bosco P, Cantarella G, Lempereur L, Di Benedetto G, Pezzino S, Bernardini R (2008) The role of antioxidant supplement in immune system, neoplastic and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile. Nutr J 30:7–29

    Google Scholar 

  18. Takeda T, Takeda S, Kakigi A, Okada T, Nishioka R, Taguchi D, Nishimura M, Nakatani H (2010) Hormonal aspects of Ménière’s disease on the basis of clinical and experimental studies. ORL J Otorhinolaryngol Relat Spec 71(Suppl 1):1–9

    PubMed  Google Scholar 

  19. Yoo TJ (2010) Dr. Takeda’s research on Ménière disease and inner ear disease. Preface. ORL J Otorhinolaryngol Relat Spec 71(Suppl 1):V

    PubMed  Google Scholar 

  20. Gonzalez Flecha B, Llesuy S, Boveris A (1991) Hydroperoxide-initiated chemiluminescence: an assay for oxidative stress in biopsies of heart, liver, and muscle. Free Radic Biol Med 10:93–100

    Article  CAS  PubMed  Google Scholar 

  21. Smith P, Krohn R, Hermanson G, Mallia A, Gartner F, Provenzano M, Fujimoto E, Goeke N, Olson B, Klenk D (1985) Measurement of proteins using bicinchoninic acid. Anal Biochem 150:76–85

    Article  CAS  PubMed  Google Scholar 

  22. Butterfield DA, Castegna A, Pocernich C, Drake J, Scapagnini G, Calabrese V (2002) Nutritional approaches to combat oxidative stress in Alzheimer’s disease. J Nutr Biochem 13:444–461

    Article  CAS  PubMed  Google Scholar 

  23. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128

    Article  CAS  PubMed  Google Scholar 

  24. Calabrese V, Poon F, Hensley K, Thongboonkerd V, Merchant M, Lynna B, Piercef WM, Kleind JB, Butterfield DA (2007) Redox proteomics analysis of oxidatively 3 modified proteins in G93A–SOD1 transgenic mice—a model of 4 familial amyotrophic lateral sclerosis. Free Radic Biol Med 43:160–162

    Article  CAS  PubMed  Google Scholar 

  25. Van Wijk R, Van Wijk EP, Wiegant FA, Ives J (2008) Free radicals and low-level photon emission in human pathogenesis: state of the art. Indian J Exp Biol 46:273–309

    PubMed  Google Scholar 

  26. Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Giuffrida A (2007) Nitric oxide in the CNS: neuroprotection vs. neurotoxicity. Nat Neurosci 8:766–775

    Article  CAS  Google Scholar 

  27. Mancuso C, Bates TE, Butterfield DA, Calafato S, Cornelius C, De Lorenzo A, Kostova AD, Calabrese V (2007) Natural antioxidants in Alzheimer’s disease. Expert. Opin Investig Drug 16:1921–1931

    Article  CAS  Google Scholar 

  28. Calabrese V, Cornelius C, Trovato A, Cavallaro M, Mancuso C, Di Rienzo L, Condorelli D, De Lorenzo A, Calabrese EJ (2010) The hormetic role of dietary antioxidants in free radical-related diseases. Curr Pharm Des 16:877–883

    Article  CAS  PubMed  Google Scholar 

  29. Calabrese V, Cornelius C, Mancuso C, Ientile R, Stella AM, Butterfield DA (2010) Redox homeostasis and cellular stress response in aging and neurodegeneration. Methods Mol Biol 610:285–308

    Article  CAS  PubMed  Google Scholar 

  30. Kawaguchi S, Hagiwara A, Suzuki M (2008) Polymorphic analysis of the heat-shock protein 70 gene (HSPA1A) in Ménière’s disease. Acta Otolaryngol 128:1173–1177

    Article  CAS  PubMed  Google Scholar 

  31. Mazurek B, Stöver T, Haupt H, Klapp BF, Adli M, Gross J, Szczepek AJ (2010) The significance of stress: its role in the auditory system and the pathogenesis of tinnitus. PMD 58:162–172

    CAS  Google Scholar 

  32. Calabrese V, Cornelius C, Rizzarelli E, Owen JB, Dinkova-Kostova AT, Butterfield DA (2009) Nitric oxide in cell survival: a janus molecule. Antioxid Redox Signal 11:2717–2739

    Article  CAS  PubMed  Google Scholar 

  33. Süslü N, Yilmaz T, Gürsel B (2009) Utility of anti-HSP 70, TNF-alpha, ESR, antinuclear antibody, and antiphospholipid antibodies in the diagnosis and treatment of sudden sensorineural hearing loss. Laryngoscope 119:341–346

    Article  PubMed  Google Scholar 

  34. Kim HJ, Lee JH, Kim SJ, Oh GS, Moon HD, Kwon KB, Park C, Park BH, Lee HK, Chung SY, Park R, So HS (2010) Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J Neuroscience 30:3933–3946

    Article  CAS  Google Scholar 

  35. Sun W, Zhang L, Lu J, Yang G, Laundrie E, Salvi R (2008) Noise exposure induced enhancement of auditory cortex response and changes in gene expression. Neuroscience 156:374–380

    Article  CAS  PubMed  Google Scholar 

  36. Fetoni AR, Mancuso C, Eramo SL, Ralli M, Piacentini R, Barone E, Paludetti G, Troiani D (2010) In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea pig. Neuroscience 48:804–810

    Google Scholar 

  37. Takumida M, Akagi N, Anniko M (2009) Effect of inner ear blood flow changes in Ménière’s model mice. Acta Otolaryngol 129:244–253

    Article  CAS  PubMed  Google Scholar 

  38. Süslü N, Yilmaz T, Gürsel B (2009) Utility of immunologic parameters in the evaluation of Meniere’s disease. Acta Otolaryngol 129:1160–1165

    Article  PubMed  Google Scholar 

  39. McNeill C, Cohen MA, Gibson WP (2009) Changes in audiometric thresholds before, during and after attacks of vertigo associated with Meniere’s syndrome. Acta Otolaryngol 129:1404–1407

    Article  PubMed  Google Scholar 

  40. Tomanovic T, Bergenius J (2010) Different types of dizziness in patients with peripheral vestibular diseases: their prevalence and relation to migraine. Acta Otolaryngol 130:1024–1030

    Article  PubMed  Google Scholar 

  41. Suslu Nilda, Yilmaz Taner, Gursel Bulent (2009) Utility of immunologic parameters in the evaluation of Meniere’s disease. Acta Otolaryngol 129:1160–1165

    Article  CAS  PubMed  Google Scholar 

  42. Fushiki H, Junicho M, Kanazawa Y, Aso S, Watanabe Y (2010) Prognosis of sudden low-tone loss other than acute low-tone sensorineural hearing loss. Acta Otolaryngol 130:559–564

    Article  PubMed  Google Scholar 

  43. Calabrese V, Cornelius C, Mancuso C, Barone E, Calafato S, Bates T, Rizzarelli E, Kostova AT (2009) Vitagenes, dietary antioxidants and neuroprotection in neurodegenerative diseases. Front Biosci 14:376–397

    Article  CAS  PubMed  Google Scholar 

  44. Trott A, West JD, Klaić L, Westerheide SD, Silverman RB, Morimoto RI, Morano KA (2008) Activation of heat shock and antioxidant responses by the natural product celastrol transcriptional signatures of a thiol-targeted molecule. Mol Biol Cell 19:1104–1112

    Article  CAS  PubMed  Google Scholar 

  45. Morimoto RI (2006) Stress, aging and neurodegenerative disease. N Engl J Med 355:2254–2255

    Article  CAS  PubMed  Google Scholar 

  46. Clerici WJ, Hensley K, DiMartino DL, Butterfield DA (1996) Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 98:116–124

    Article  CAS  PubMed  Google Scholar 

  47. Prasad R, Kawaguchi S (2010) A nucleus-based quality control mechanism for cytosolic proteins. Mol Biol Cell 21:2117–2127

    Article  CAS  PubMed  Google Scholar 

  48. Klausz G, Molnar T, Nagy F, Gyulai Z, Boda K, Lonovics J et al (2005) Polymorphism of the heat-shock protein gene Hsp70–2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn’s disease. Scand J Gastroenterol 40:1197–1204

    Article  CAS  PubMed  Google Scholar 

  49. Sultana R, Perluigi M, Newman SF, Pierce WM, Cini C, Coccia R, Butterfield DA (2010) Redox proteomic analysis of carbonylated brain proteins in mild cognitive impairment and early Alzheimer’s disease. Antioxid Redox Signal 12:327–336

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Work from the authors’ laboratories was supported by grants from MIUR, FIRB RBRN07BMCT, INBB and by ‘‘Fondi Ateneo’’ 2007 and 2008.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Medicine, University of Catania, Catania, Italy

    Vittorio Calabrese, C. Cornelius & M. Luca

  2. Department of Chemistry, Biochemistry Mol. Biology Section, Faculty of Medicine, University of Catania, Catania, Italy

    Vittorio Calabrese

  3. Department of Biomedical Science, Faculty of Medicine, University of Catania, Catania, Italy

    M. A. Toscano

  4. Department of Medical and Surgery Specialties, ENT Section, Faculty of Medicine, University of Catania, Catania, Italy

    L. Maiolino, R. Chiaramonte & A. Serra

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  1. Vittorio Calabrese
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  2. C. Cornelius
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  3. L. Maiolino
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  4. M. Luca
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  5. R. Chiaramonte
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  6. M. A. Toscano
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  7. A. Serra
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Correspondence to Vittorio Calabrese.

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We are very much honoured to contribute to this Special Issue in honour of Abel Lajtha. Everybody in the field of Neurochemistry knows Abel Lajtha and his great contribution to the advancement of research in Neurochemistry. We would like to thank him very much for his great contribution to the advancement and success of Neurochemical Research and ask him to continue his precious work helping us with its seminal effort.

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Calabrese, V., Cornelius, C., Maiolino, L. et al. Oxidative Stress, Redox Homeostasis and Cellular Stress Response in Ménière’s Disease: Role of Vitagenes. Neurochem Res 35, 2208–2217 (2010). https://doi.org/10.1007/s11064-010-0304-2

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