1887

Abstract

Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, 1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that 1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with 1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator.

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2015-01-01
2019-10-22
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References

  1. Bagley J., Singh G., Iacomini J.. ( 2007;). Regulation of oxidative stress responses by ataxia-telangiectasia mutated is required for T cell proliferation. . J Immunol 178:, 4757–4763. [CrossRef][PubMed]
    [Google Scholar]
  2. Behrens M. M., Ali S. S., Dao D. N., Lucero J., Shekhtman G., Quick K. L., Dugan L. L.. ( 2007;). Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. . Science 318:, 1645–1647. [CrossRef][PubMed]
    [Google Scholar]
  3. Bensaad K., Vousden K. H.. ( 2005;). Savior and slayer: the two faces of p53. . Nat Med 11:, 1278–1279. [CrossRef][PubMed]
    [Google Scholar]
  4. Bensaad K., Tsuruta A., Selak M. A., Vidal M. N., Nakano K., Bartrons R., Gottlieb E., Vousden K. H.. ( 2006;). TIGAR, a p53-inducible regulator of glycolysis and apoptosis. . Cell 126:, 107–120. [CrossRef][PubMed]
    [Google Scholar]
  5. Burdon R. H., Alliangana D., Gill V.. ( 1995;). Hydrogen peroxide and the proliferation of BHK-21 cells. . Free Radic Res 23:, 471–486. [CrossRef][PubMed]
    [Google Scholar]
  6. Daniel R., Pomerantz R. J.. ( 2005;). ATM: HIV-1’s Achilles heel. ? Nat Cell Biol 7:, 452–453. [CrossRef][PubMed]
    [Google Scholar]
  7. de la Fuente C., Maddukuri A., Kehn K., Baylor S. Y., Deng L., Pumfery A., Kashanchi F.. ( 2003;). Pharmacological cyclin-dependent kinase inhibitors as HIV-1 antiviral therapeutics. . Curr HIV Res 1:, 131–152. [CrossRef][PubMed]
    [Google Scholar]
  8. Deng X., Gao F., May W. S. Jr. ( 2003;). Bcl2 retards G1/S cell cycle transition by regulating intracellular ROS. . Blood 102:, 3179–3185. [CrossRef][PubMed]
    [Google Scholar]
  9. Doitsh G., Galloway N. L., Geng X., Yang Z., Monroe K. M., Zepeda O., Hunt P. W., Hatano H., Sowinski S.. & other authors ( 2014;). Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. . Nature 505:, 509–514. [CrossRef][PubMed]
    [Google Scholar]
  10. Ehsan A., Fan H., Eagan P. A., Siddiqui H. A., Gulley M. L.. ( 2000;). Accumulation of p53 in infectious mononucleosis tissues. . Hum Pathol 31:, 1397–1403. [CrossRef][PubMed]
    [Google Scholar]
  11. Foli A., Maiocchi M. A., Lisziewicz J., Lori F.. ( 2007;). A checkpoint in the cell cycle progression as a therapeutic target to inhibit HIV replication. . J Infect Dis 196:, 1409–1415. [CrossRef][PubMed]
    [Google Scholar]
  12. Garden G. A., Guo W., Jayadev S., Tun C., Balcaitis S., Choi J., Montine T. J., Möller T., Morrison R. S.. ( 2004;). HIV associated neurodegeneration requires p53 in neurons and microglia. . FASEB J 18:, 1141–1143.[PubMed]
    [Google Scholar]
  13. Guo Z., Kozlov S., Lavin M. F., Person M. D., Paull T. T.. ( 2010;). ATM activation by oxidative stress. . Science 330:, 517–521. [CrossRef][PubMed]
    [Google Scholar]
  14. Havens C. G., Ho A., Yoshioka N., Dowdy S. F.. ( 2006;). Regulation of late G1/S phase transition and APC Cdh1 by reactive oxygen species. . Mol Cell Biol 26:, 4701–4711. [CrossRef][PubMed]
    [Google Scholar]
  15. Hu W., Zhang C., Wu R., Sun Y., Levine A., Feng Z.. ( 2010;). Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. . Proc Natl Acad Sci U S A 107:, 7455–7460. [CrossRef][PubMed]
    [Google Scholar]
  16. Iiyama M., Kakihana K., Kurosu T., Miura O.. ( 2006;). Reactive oxygen species generated by hematopoietic cytokines play roles in activation of receptor-mediated signaling and in cell cycle progression. . Cell Signal 18:, 174–182. [CrossRef][PubMed]
    [Google Scholar]
  17. Jayadev S., Yun B., Nguyen H., Yokoo H., Morrison R. S., Garden G. A.. ( 2007;). The glial response to CNS HIV infection includes p53 activation and increased expression of p53 target genes. . J Neuroimmune Pharmacol 2:, 359–370. [CrossRef][PubMed]
    [Google Scholar]
  18. Jiang Y., Scofield V. L., Yan M., Qiang W., Liu N., Reid A. J., Lynn W. S., Wong P. K.. ( 2006;). Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by anti-oxidant treatment with a refined monosodium alpha luminol (Galavit). . J Virol 80:, 28–37.
    [Google Scholar]
  19. Jones G. J., Barsby N. L., Cohen E. A., Holden J., Harris K., Dickie P., Jhamandas J., Power C.. ( 2007;). HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration. . J Neurosci 27:, 3703–3711. [CrossRef][PubMed]
    [Google Scholar]
  20. Kim J., Wong P. K.. ( 2009a;). Loss of ATM impairs proliferation of neural stem cells through oxidative stress-mediated p38 MAPK signaling. . Stem Cells 27:, 1987–1998. [CrossRef][PubMed]
    [Google Scholar]
  21. Kim J., Wong P. K.. ( 2009b;). Oxidative stress is linked to ERK1/2-p16 signaling-mediated growth defect in ATM-deficient astrocytes. . J Biol Chem 284:, 14396–14404. [CrossRef][PubMed]
    [Google Scholar]
  22. Kim S. J., Wong P. K.. ( 2013;). ROS upregulation during the early phase of retroviral infection plays an important role in viral establishment in the host cell. . J Gen Virol 94:, 2309–2317. [CrossRef][PubMed]
    [Google Scholar]
  23. Kim H. T., Tasca S., Qiang W., Wong P. K., Stoica G.. ( 2002;). Induction of p53 accumulation by Moloney murine leukemia virus-ts1 infection in astrocytes via activation of extracellular signal-regulated kinases 1/2. . Lab Invest 82:, 693–702. [CrossRef][PubMed]
    [Google Scholar]
  24. Kuang X., Hu W., Yan M., Wong P. K.. ( 2010;). Phenylbutyric acid suppresses protein accumulation-mediated ER stress in retrovirus-infected astrocytes and delays onset of paralysis in infected mice. . Neurochem Int 57:, 738–748. [CrossRef][PubMed]
    [Google Scholar]
  25. Lau A., Swinbank K. M., Ahmed P. S., Taylor D. L., Jackson S. P., Smith G. C., O’Connor M. J.. ( 2005;). Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase. . Nat Cell Biol 7:, 493–500. [CrossRef][PubMed]
    [Google Scholar]
  26. Lin Y. C., Chow C. W., Yuen P. H., Wong P. K.. ( 1997;). Establishment and characterization of conditionally immortalized astrocytes to study their interaction with ts1, a neuropathogenic mutant of Moloney murine leukemia virus. . J Neurovirol 3:, 28–37. [CrossRef][PubMed]
    [Google Scholar]
  27. Louboutin J. P., Agrawal L., Reyes B. A., Van Bockstaele E. J., Strayer D. S.. ( 2007;). Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors. . Gene Ther 14:, 1650–1661. [CrossRef][PubMed]
    [Google Scholar]
  28. Mukerjee R., Deshmane S. L., Fan S., Del Valle L., White M. K., Khalili K., Amini S., Sawaya B. E.. ( 2008;). Involvement of the p53 and p73 transcription factors in neuroAIDS. . Cell Cycle 7:, 2682–2690. [CrossRef][PubMed]
    [Google Scholar]
  29. Nardacci R., Antinori A., Larocca L. M., Arena V., Amendola A., Perfettini J. L., Kroemer G., Piacentini M.. ( 2005;). Characterization of cell death pathways in human immunodeficiency virus-associated encephalitis. . Am J Pathol 167:, 695–704. [CrossRef][PubMed]
    [Google Scholar]
  30. Noorbakhsh F., Ramachandran R., Barsby N., Ellestad K. K., LeBlanc A., Dickie P., Baker G., Hollenberg M. D., Cohen E. A., Power C.. ( 2010;). MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival. . FASEB J 24:, 1799–1812. [CrossRef][PubMed]
    [Google Scholar]
  31. Olivetta E., Pietraforte D., Schiavoni I., Minetti M., Federico M., Sanchez M.. ( 2005;). HIV-1 Nef regulates the release of superoxide anions from human macrophages. . Biochem J 390:, 591–602. [CrossRef][PubMed]
    [Google Scholar]
  32. Olivetta E., Mallozzi C., Ruggieri V., Pietraforte D., Federico M., Sanchez M.. ( 2009;). HIV-1 Nef induces p47(phox) phosphorylation leading to a rapid superoxide anion release from the U937 human monoblastic cell line. . J Cell Biochem 106:, 812–822. [CrossRef][PubMed]
    [Google Scholar]
  33. Olovnikov I. A., Kravchenko J. E., Chumakov P. M.. ( 2009;). Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense. . Semin Cancer Biol 19:, 32–41. [CrossRef][PubMed]
    [Google Scholar]
  34. Purvis J. E., Karhohs K. W., Mock C., Batchelor E., Loewer A., Lahav G.. ( 2012;). p53 dynamics control cell fate. . Science 336:, 1440–1444. [CrossRef][PubMed]
    [Google Scholar]
  35. Qiang W., Cahill J. M., Liu J., Kuang X., Liu N., Scofield V. L., Voorhees J. R., Reid A. J., Yan M.. & other authors ( 2004;). Activation of transcription factor Nrf-2 and its downstream targets in response to moloney murine leukemia virus ts1-induced thiol depletion and oxidative stress in astrocytes. . J Virol 78:, 11926–11938. [CrossRef][PubMed]
    [Google Scholar]
  36. Qiang W., Kuang X., Liu J., Liu N., Scofield V. L., Reid A. J., Jiang Y., Stoica G., Lynn W. S., Wong P. K.. ( 2006;). Astrocytes survive chronic infection and cytopathic effects of the ts1 mutant of the retrovirus Moloney murine leukemia virus by upregulation of antioxidant defenses. . J Virol 80:, 3273–3284. [CrossRef][PubMed]
    [Google Scholar]
  37. Ranjan P., Anathy V., Burch P. M., Weirather K., Lambeth J. D., Heintz N. H.. ( 2006;). Redox-dependent expression of cyclin D1 and cell proliferation by Nox1 in mouse lung epithelial cells. . Antioxid Redox Signal 8:, 1447–1459. [CrossRef][PubMed]
    [Google Scholar]
  38. Rhee S. G.. ( 2006;). Cell signaling. H2O2, a necessary evil for cell signaling. . Science 312:, 1882–1883. [CrossRef][PubMed]
    [Google Scholar]
  39. Sablina A. A., Budanov A. V., Ilyinskaya G. V., Agapova L. S., Kravchenko J. E., Chumakov P. M.. ( 2005;). The antioxidant function of the p53 tumor suppressor. . Nat Med 11:, 1306–1313. [CrossRef][PubMed]
    [Google Scholar]
  40. Salmen S., Colmenares M., Peterson D. L., Reyes E., Rosales J. D., Berrueta L.. ( 2010;). HIV-1 Nef associates with p22-phox, a component of the NADPH oxidase protein complex. . Cell Immunol 263:, 166–171. [CrossRef][PubMed]
    [Google Scholar]
  41. Sattler M., Winkler T., Verma S., Byrne C. H., Shrikhande G., Salgia R., Griffin J. D.. ( 1999;). Hematopoietic growth factors signal through the formation of reactive oxygen species. . Blood 93:, 2928–2935.[PubMed]
    [Google Scholar]
  42. Schubert R., Erker L., Barlow C., Yakushiji H., Larson D., Russo A., Mitchell J. B., Wynshaw-Boris A.. ( 2004;). Cancer chemoprevention by the antioxidant tempol in Atm-deficient mice. . Hum Mol Genet 13:, 1793–1802. [CrossRef][PubMed]
    [Google Scholar]
  43. Suzuki S., Tanaka T., Poyurovsky M. V., Nagano H., Mayama T., Ohkubo S., Lokshin M., Hosokawa H., Nakayama T.. & other authors ( 2010;). Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. . Proc Natl Acad Sci U S A 107:, 7461–7466. [CrossRef][PubMed]
    [Google Scholar]
  44. Szatrowski T. P., Nathan C. F.. ( 1991;). Production of large amounts of hydrogen peroxide by human tumor cells. . Cancer Res 51:, 794–798.[PubMed]
    [Google Scholar]
  45. Wong P. K., Knupp C., Yuen P. H., Soong M. M., Zachary J. F., Tompkins W. A.. ( 1985;). ts1, a Paralytogenic mutant of Moloney murine leukemia virus TB, has an enhanced ability to replicate in the central nervous system and primary nerve cell culture. . J Virol 55:, 760–767.[PubMed]
    [Google Scholar]
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