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The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system

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Abstract

Herein, we investigate whether the NADPH oxidase might be playing a key role in the degree of oxidative stress in the senescence-accelerated mouse prone-8 (SAM-P8). To this end, the activity and expression of the NADPH oxidase, the ratio of glutathione and glutathione disulfides (GSH/GSSG), and the levels of malonyl dialdehyde (MDA) and nitrotyrosine (NT) were determined in renal tissue from SAM-P8 mice at the age of 1 and 6 months. The senescence-accelerated-resistant mouse (SAM-R1) was used as control. At the age of 1 month, NADPH oxidase activity and Nox2 protein expression were higher in SAM-P8 than in SAM-R1 mice. However, we found no differences in the GSH/GSSG ratio, MDA, NT, and Nox4 levels between both groups of animals. At the age of 6 months, SAM-R1 mice in comparison to SAM-P8 mice showed an increase in NADPH oxidase activity, which is associated with higher levels of NT and increased Nox4 and Nox2 expression levels. Furthermore, we found oxidative stress hallmarks including depletion in GSH/GSSG ratio and increase in MDA levels in the kidney of SAM-P8 mice. Finally, NADPH oxidase activity positively correlated with Nox2 expression in all the animals (r = 0.382, P < 0.05). Taken together, our data allow us to suggest that an increase in NADPH oxidase activity might be an early hallmark to predict future oxidative stress in renal tissue during the aging process that takes place in SAM-P8 mice.

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References

  1. Alvarez-Garcia O, Vega-Naredo I, Sierra V, Caballero B, Tomas-Zapico C, Camins A, Garcia JJ, Pallas M, Coto-Montes A (2006) Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age. Biogerontology 7:43–52

    Article  PubMed  CAS  Google Scholar 

  2. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495

    Article  PubMed  CAS  Google Scholar 

  3. Baltanás A, Miguel-Carrasco JL, San José G, Cebrián C, Dotor J, Moreno MD, Borrás-Cuesta F, López B, Gonzalez A, Díez J, Fortuño A, Zalba G (2013) A synthetic peptide from transforming growth factor-beta1 type III receptor inhibits NADPH oxidase and prevents oxidative stress in the kidney of spontaneously hypertensive rats. Antioxid Redox Signal (in press)

  4. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313

    Article  PubMed  CAS  Google Scholar 

  5. Bokoch GM, Knaus UG (2003) NADPH oxidases: not just for leukocytes anymore! Trends Biochem Sci 28:502–508

    Article  PubMed  CAS  Google Scholar 

  6. Briones AM, Touyz RM (2010) Oxidative stress and hypertension: current concepts. Curr Hypertens Rep 12:135–142

    Article  PubMed  CAS  Google Scholar 

  7. Chabrashvili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ, Wilcox CS (2002) Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension 39:269–274

    Article  PubMed  CAS  Google Scholar 

  8. Chiba Y, Shimada A, Kumagai N, Yoshikawa K, Ishii S, Furukawa A, Takei S, Sakura M, Kawamura N, Hosokawa M (2009) The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model. Neurochem Res 34:679–687

    Article  PubMed  CAS  Google Scholar 

  9. Dikalov SI, Dikalova AE, Bikineyeva AT, Schmidt HH, Harrison DG, Griendling KK (2008) Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med 45:1340–1351

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Folkow B, Svanborg A (1993) Physiology of cardiovascular aging. Physiol Rev 73:725–764

    PubMed  CAS  Google Scholar 

  12. Forman K, Vara E, Garcia C, Ariznavarreta C, Escames G, Tresguerres JA (2010) Cardiological aging in SAM model: effect of chronic treatment with growth hormone. Biogerontology 11:275–286

    Article  PubMed  CAS  Google Scholar 

  13. Geiszt M, Kopp JB, Varnai P, Leto TL (2000) Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci U S A 97:8010–8014

    Article  PubMed  CAS  Google Scholar 

  14. Gomez-Lazaro M, Galindo MF, Melero-Fernandez de Mera RM, Fernandez-Gomez FJ, Concannon CG, Segura MF, Comella JX, Prehn JH, Jordan J (2007) Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to induce mitochondrial cytochrome c release and apoptosis in response to malonate. Mol Pharmacol 71:736–743

    Article  PubMed  CAS  Google Scholar 

  15. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300

    Article  PubMed  CAS  Google Scholar 

  16. Harman D (2006) Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci 1067:10–21

    Article  PubMed  CAS  Google Scholar 

  17. Hosokawa M (2002) A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice. Mech Ageing Dev 123:1553–1561

    Article  PubMed  CAS  Google Scholar 

  18. Jacobson A, Yan C, Gao Q, Rincon-Skinner T, Rivera A, Edwards J, Huang A, Kaley G, Sun D (2007) Aging enhances pressure-induced arterial superoxide formation. Am J Physiol Heart Circ Physiol 293:H1344–1350

    Article  PubMed  CAS  Google Scholar 

  19. Jordan J, Galindo MF, Tornero D, Benavides A, Gonzalez C, Agapito MT, Gonzalez-Garcia C, Cena V (2002) Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells. Br J Pharmacol 137:993–1000

    Article  PubMed  CAS  Google Scholar 

  20. Krause KH (2007) Aging: a revisited theory based on free radicals generated by NOX family NADPH oxidases. Exp Gerontol 42:256–262

    Article  PubMed  CAS  Google Scholar 

  21. Kung CF, Luscher TF (1995) Different mechanisms of endothelial dysfunction with aging and hypertension in rat aorta. Hypertension 25:194–200

    Article  PubMed  CAS  Google Scholar 

  22. Llorens S, Salazar FJ, Nava E (2005) Assessment of the nitric oxide system in the heart, aorta and kidney of aged Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens 23:1507–1514

    Article  PubMed  CAS  Google Scholar 

  23. Llorens S, de Mera RM, Pascual A, Prieto-Martin A, Mendizabal Y, de Cabo C, Nava E, Jordan J (2007) The senescence-accelerated mouse (SAM-P8) as a model for the study of vascular functional alterations during aging. Biogerontology 8:663–672

    Article  PubMed  CAS  Google Scholar 

  24. Quinn MT, Ammons MC, Deleo FR (2006) The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction. Clin Sci (Lond) 111:1–20

    Article  CAS  Google Scholar 

  25. Rebrin I, Zicker S, Wedekind KJ, Paetau-Robinson I, Packer L, Sohal RS (2005) Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse. Free Radic Biol Med 39:549–557

    Article  PubMed  CAS  Google Scholar 

  26. Schnelldorfer T, Gansauge S, Gansauge F, Schlosser S, Beger HG, Nussler AK (2000) Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells. Cancer 89:1440–1447

    Article  PubMed  CAS  Google Scholar 

  27. Schluter T, Grimm R, Steinbach A, Lorenz G, Rettig R, Grisk O (2006) Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys. Am J Physiol Regul Integr Comp Physiol 291:R391–R399

    Article  PubMed  Google Scholar 

  28. Si F, Ross GM, Shin SH (1998) Glutathione protects PC12 cells from ascorbate- and dopamine-induced apoptosis. Exp Brain Res 123:263–268

    Article  PubMed  CAS  Google Scholar 

  29. Sies H (1993) Strategies of antioxidant defense. Eur J Biochem 215:213–219

    Article  PubMed  CAS  Google Scholar 

  30. Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T, Tomita Y, Yasuhira K, Hamamoto H, Shimizu K, Ishii M, Yamamuro T (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17:183–194

    Article  PubMed  CAS  Google Scholar 

  31. Touyz RM, Briones AM, Sedeek M, Burger D, Montezano AC (2011) NOX isoforms and reactive oxygen species in vascular health. Mol Interv 11:27–35

    Article  PubMed  CAS  Google Scholar 

  32. Yamashita Y, Chiba Y, Xia C, Hirayoshi K, Satoh M, Saitoh Y, Shimada A, Nakamura E, Hosokawa M (2005) Different adaptive traits to cold exposure in young senescence-accelerated mice. Biogerontology 6:133–139

    Article  PubMed  Google Scholar 

  33. Zieman SJ, Gerstenblith G, Lakatta EG, Rosas GO, Vandegaer K, Ricker KM, Hare JM (2001) Upregulation of the nitric oxide-cGMP pathway in aged myocardium: physiological response to l-arginine. Circ Res 88:97–102

    Article  PubMed  CAS  Google Scholar 

  34. Zhang JJ, Bledsoe G, Kato K, Chao L, Chao J (2004) Tissue kallikrein attenuates salt-induced renal fibrosis by inhibition of oxidative stress. Kidney Int 66:722–732

    Article  PubMed  CAS  Google Scholar 

  35. Zhou X, Frohlich ED (2003) Ageing, hypertension and the kidney: new data on an old problem. Nephrol Dial Transplant 18:1442–1445

    Article  PubMed  Google Scholar 

  36. Zhou MS, Schuman IH, Jaimes EA, Raij L (2008) Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF-beta, and fibronectin with concomitant increase in nitric oxide bioavailability. Am J Physiol Renal Physiol 295:F53–F59

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to Carlos Garrido, Sandra Arteaga, Ana Montoya, and Idoia Rodríguez for technical assistance. This work was supported by the agreement between the Foundation for Applied Medical Research (FIMA) and UTE project CIMA, RECAVA from the Instituto de Salud Carlos III, Ministry of Health, SAF2011-29610 from Ministry of Science (to A.F.), SAF 2008-05143-C03-1 from CICYT (to J.J.), SAF2010-20367 from CICYT (to G.Z.), and by PI11/00736 FIS CARLOS III (to M.F.G.).

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Authors and Affiliations

  1. Division of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, Pío XII 55, 31008, Pamplona, Spain

    Ana Baltanás, Guillermo Zalba & Ana Fortuño

  2. Translational Neuropsychopharmacology Unit, Albacete University Hospital Center, Albacete, Spain

    Maria E. Solesio & María F. Galindo

  3. Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain

    Guillermo Zalba

  4. Pharmaceutical Technology, Department of Medical Sciences, University of Castilla–La Mancha, Albacete, Spain

    María F. Galindo

  5. Department of Medical Sciences, University of Castilla-La Mancha School of Medicine, Almansa 14, 02006, Albacete, Spain

    Joaquín Jordán

  6. Neuropharmacology Group, University of Castilla–La Mancha, Albacete, Spain

    Joaquín Jordán

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  1. Ana Baltanás
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  2. Maria E. Solesio
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  3. Guillermo Zalba
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  4. María F. Galindo
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  6. Joaquín Jordán
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Correspondence to Ana Fortuño or Joaquín Jordán.

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Baltanás, A., Solesio, M.E., Zalba, G. et al. The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system. J Physiol Biochem 69, 927–935 (2013). https://doi.org/10.1007/s13105-013-0271-6

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  • DOI: https://doi.org/10.1007/s13105-013-0271-6

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