Caracterización bioquímica del nervio óptico en el ratón que sobreexpresa el gen P53análisis de estrés oxidativo

  1. R. Gallego-Pinazo
  2. V. Zanón-Moreno
  3. S. Sanz
  4. V. Andrés
  5. M. Serrano
  6. I. García-Cao
  7. M.D. Pinazo-Durán
Journal:
Archivos de la Sociedad Española de Oftalmologia

ISSN: 0365-6691

Year of publication: 2008

Volume: 83

Issue: 2

Pages: 105-112

Type: Article

DOI: 10.4321/S0365-66912008000200008 DIALNET GOOGLE SCHOLAR lock_openOpen access editor

More publications in: Archivos de la Sociedad Española de Oftalmologia

Abstract

Purpose: The tumour inhibitor p53 gene has the ability of triggering proliferation arrest and cellular death by apoptosis subsequent to several factors, among them oxidative stress. The p53 protein is a major regulator of gene expression. Using genetically manipulated mice carrying an extra copy of gene p53 (transgenic mice super p53) versus control mice, we have investigated the generation of reactive oxygen species and antioxidant activity in the optic nerve of mice in relation to p53 availability. Methods: We studied two groups of 12-month-old mice of the strain C57BL/6: 1) super p53 group (Sp53) and 2) wild-type control group (CG). Mice were anesthetized in ether atmosphere and the eyeball and retrobulbar optic nerves were excised, washed, soaked in PBS, and stored in liquid nitrogen at -85ºC until processing. Three-four optic nerves from the same group were placed in an eppendorf tube, homogenized and enzymatic-colorimetric methods used to determine oxidative and antioxidant activities and the nitric oxide synthesis. Results: A significant increase in free radical formation (via lipid peroxidation; p<0.001), antioxidant activity (p<0.001) and nitric oxide synthesis (p<0.001) was found in the optic nerves from transgenic super p53 mice compared to respective controls. Conclusion: The presence of an extra copy of the p53 gene correlated with redox status in the mouse optic nerve. This transgenic mouse could be useful as an experimental model to study cell resistance to neurodegenerative processes in relation to oxidative stress and to apoptosis induction, such as glaucomatous optic neuropathy or age-related macular degeneration.

Bibliographic References

  • Muñoz, A. (1997). Genes supresores de tumores y genes de reparación del DNA. Editorial Hélice. Madrid.
  • Zavaglia, D, Lin, EH, Guidetti, M, Pluquet, O, Hianaut, P, Favrot, MC. (2005). Poor intercellular transport and abscence of enhanced antiproliferative activity alter non-viral gene transfer of VP22-P53 or P53-VP22 fusions into p53 null cell lines in vitro or in vivo. J Gene Med. 7. 936-944
  • García-Cao, I, Carcía-Cao, M, Martín-Caballero, J, Criado, LK, Klatt, P, Flores, JM, et, al. (2002). «Super p53» mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 21. 6225-6235
  • Steller, H. (1995). Mechanisms and genes of cellular suicide. Science. 267. 1445-1449
  • Odin, L, Favrot, M, Poujol, D, Mitchot, JP, Moingeon, P, Tartaglia, J. (2001). Canarypox virus expressing wild type p53 for gene therapy in murine tumors mutated in p53. Cancer Gene Ther. 8. 87-98
  • Boultwood, J. (2001). Ataxia telangiectasia gene mutations in leukaemia and lymphoma. J Clin Pathol. 54. 512-516
  • Bates, S, Voudsen, KH. (1996). P53 in signaling checkpoint arrest or apoptosis. Curr Opin Genet Dev. 6. 12-18
  • Lotem, J, Peled-Kamar, M, Groner, Y, Sachs, L. (1996). Cellular oxidative stress and the control of apoptosis by wild type p53, cytotoxic compounds and cytokines. Proctl Natl Acad Sci USA. 93. 9166-9171
  • Raff, MC. (1992). Social controls on cell survival and cell death. Nature. 356. 397-400
  • Guo, L, Moss, SE, Alexander, RA, Ali, RR, Fitzke, FW, Cordeiro, MF. (2005). Retinal glanglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix. Invest Ophthalmol Vis Sci. 46. 175-182
  • Kerrigan, LA, Zack, DJ, Quigley, HA, Smith, SD, Pease, ME. (1997). TUNEL-positive ganglion cell in human primary open-angle glaucoma. Arch Ophthalmol. 115. 1031-1035
  • Wu, LY, Hinton, DR, Guo, L, Jiang, S, Wang, JT, Zeng, A. (2003). Microphtalmia resulting from MSX2-induced apoptosis in the optic vesicle. Invest Ophthalmol Vis Sci. 44. 2404-2412
  • Strömland, K, Pinazo-Duran, MD. (1994). Optic nerve hypoplasia: comparative effects in children and rats exposed to alcohol during pregnancy. Teratology. 50. 100-111
  • Pinazo-Duran, MD, Renau, J, Guerri, C, Strömland, K. (1997). Optic nerve hypoplasia in fetal alcohol syndrome: an update. Eur J Ophthalmol. 7. 262-270
  • Strömland, K, Pinazo-Duran, MD. (2002). Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies. Alcohol Alcohol. 37. 2-8
  • Pinazo-Duran, MD, Iborra, JF, Pons, S, Sevilla, E, Gallego-Pinazo, R, Muñoz, A. (2002). Postnatal thyroid hormone supplementation rescues developmental abnormalities induced by congenital-neonatal hypothyroidism in the rat retina. Ophthalmic Res. 37. 225-234
  • Melo, P, Rodrigues, LG, Pinazo-Duran, MD, Tavares, MA. (2005). Methamphetamine and lipid peroxidation in the rat retina. Birth Defects Res A Clin Mol Teratol. 73. 455-460
  • Pinazo-Duran, MD, Cervera, R, Pons, S, Zanon, VC, Gallego-Pinazo, R, Guerri, C. (2005). Mecanismos de expresión proteica en el nervio óptico de la rata. Arch Soc Esp Oftalmol. 80. 99-104
  • Lowe, SW, Bodis, S, McClatchey,, Remington L, Ruley, HE, Fisher, DE. (1994). p53 status and the efficacy of cancer therapy in vivo. Science. 266. 807-810
  • Neufeld, AH, Sawada, A, Becker, B. (1999). Inhibition of nitric oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat miodel of chronic glaucoma. Proctl Natl Acad Sci USA. 96. 9944-9948
  • Wang, X, Zalcenstein, A, Oren, M. (2003). Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation. Cell Death Differ. 10. 468-476
  • Forrester, K, Ambs, S, Lupold, SE, Kapust, RB, Spillare, EA, Weinberg, WC. (1996). Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild type p53. Proctl Natl Acad Sci USA. 93. 2442-2447
Data source: Dialnet