Journal of Neuroimmunology
Volume 171, Issue 1 , Pages 17-28 , February 2006

Methylmercury causes oxidative stress and cytotoxicity in microglia: Attenuation by 15-deoxy-delta 12, 14-Prostaglandin J2

  • Tarun K. Garg

      Affiliations

    • Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA
  • ,
  • Jason Y. Chang

      Affiliations

    • Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA
    • Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA
    • Corresponding Author InformationCorresponding author. Department of Neurobiology and Developmental Sciences, Slot 510, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA. Tel.: +1 501 686 7025; fax: +1 501 686 6382.

Received 1 June 2005 ,Accepted 13 September 2005.

References 

  1. Ali SF, LeBel CP, Bondy SC. Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology. 1992;13:637–648
  2. Allen JW, El-Oqayli H, Aschner M, Syversen T, Sonnewald U. Methylmercury has a selective effect on mitochondria in cultured astrocytes in the presence of [U-(13)C]glutamate. Brain Res. 2001;908:149–154
  3. Aschner M, Allen JW, Kimelberg HK, LoPachin RM, Streit WJ. Glial cells in neurotoxicity development. Annu. Rev. Pharmacol. Toxicol. 1999;39:151–173
  4. Baeyens W, Leermakers M, Papina T, Saprykin A, Brion N, Noyen J, et al. Bioconcentration and biomagnification of mercury and methylmercury in North Sea and Scheldt estuary fish. Arch. Environ. Contam. Toxicol. 2003;45:498–508
  5. Baldwin DR, Marshall WJ. Heavy metal poisoning and its laboratory investigation. Ann. Clin. Biochem. 1999;36(Pt 3):267–300
  6. Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature. 1997;388:878–881
  7. Barron KD. The microglial cell. A historical review. J. Neurol. Sci. 1995;134:57–68
  8. Bonzongo JC, Heim KJ, Warwick JJ, Lyons WB. Mercury levels in surface waters of the Carson River-Lahontan reservoir system, Nevada: influence of historic mining activities. Environ. Pollut. 1996;92:193–201
  9. Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC. Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J. Immunol. 1999;163:3963–3968
  10. Castoldi AF, Barni S, Turin I, Gandini C, Manzo L. Early acute necrosis, delayed apoptosis and cytoskeletal breakdown in cultured cerebellar granule neurons exposed to methylmercury. J. Neurosci. Res. 2000;59:775–787
  11. Chang JY, Liu L. Peroxisome proliferator-activated receptor agoinsts prevent 25-OH-cholesterol induced c-jun activation and cell death. BMC Pharmacol. 2001;1:10
  12. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury—current exposures and clinical manifestations. N. Engl. J. Med. 2003;349:1731–1737
  13. Conroy SM, Nguyen V, Quina LA, Blakely-Gonzales P, Ur C, Netzeband JG, et al. Interleukin-6 produces neuronal loss in developing cerebellar granule neuron cultures. J. Neuroimmunol. 2004;155:43–54
  14. Corradin SB, Mauel J, Donini SD, Quattrocchi E, Ricciardi-Castagnoli P. Inducible nitric oxide synthase activity of cloned murine microglial cells. Glia. 1993;7:255–262
  15. Davies SS, Pontsler AV, Marathe GK, Harrison KA, Murphy RC, Hinshaw JC, et al. Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor gamma ligands and agonists. J. Biol. Chem. 2001;276:16015–16023
  16. Dhanasekaran A, Kotamraju S, Kalivendi SV, Matsunaga T, Shang T, Keszler A, et al. Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis. J. Biol. Chem. 2004;279:37575–37587
  17. Domagalski JL, Alpers CN, Slotton DG, Suchanek TH, Ayers SM. Mercury and methylmercury concentrations and loads in the Cache Creek watershed, California. Sci. Total Environ. 2004;327:215–237
  18. Eskes C, Honegger P, Juillerat-Jeanneret L, Monnet-Tschudi F. Microglial reaction induced by noncytotoxic methylmercury treatment leads to neuroprotection via interactions with astrocytes and IL-6 release. Glia. 2002;37:43–52
  19. Gadient RA, Otten UH. Interleukin-6 (IL-6)—a molecule with both beneficial and destructive potentials. Prog. Neurobiol. 1997;52:379–390
  20. Gardner PR, Nguyen DD, White CW. Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. Proc. Natl. Acad. Sci. U. S. A. 1994;91:12248–12252
  21. Gardner PR, Raineri I, Epstein LB, White CW. Superoxide radical and iron modulate aconitase activity in mammalian cells. J. Biol. Chem. 1995;270:13399–13405
  22. Garg TK, Chang JY. Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ2. BMC Ophthalmol. 2003;3:5
  23. Garg TK, Chang JY. 15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress. BMC Pharmacol. 2004;4:6
  24. Gijbels K, Van Damme J, Proost P, Put W, Carton H, Billiau A. Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis. Eur. J. Immunol. 1990;20:233–235
  25. Gray JE, Theodorakos PM, Bailey EA, Turner RR. Distribution, speciation, and transport of mercury in stream-sediment, stream-water, and fish collected near abandoned mercury mines in southwestern Alaska, USA. Sci. Total Environ. 2000;260:21–33
  26. Harris HH, Pickering IJ, George GN. The chemical form of mercury in fish. Science. 2003;301:1203
  27. Hickey WF, Vass K, Lassmann H. Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J. Neuropathol. Exp. Neurol. 1992;51:246–256
  28. InSug O, Datar S, Koch CJ, Shapiro IM, Shenker BJ. Mercuric compounds inhibit human monocyte function by inducing apoptosis: evidence for formation of reactive oxygen species, development of mitochondrial membrane permeability transition and loss of reductive reserve. Toxicology. 1997;124:211–224
  29. James SJ, Slikker W, Melnyk S, New E, Pogribna M, Jernigan S. Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxicology. 2005;26:1–8
  30. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998;391:82–86
  31. Kempermann G, Neumann H. Microglia: the enemy within?. Science. 2003;302:1689–1690
  32. Kim SH, Sharma RP. Cytotoxicity of inorganic mercury in murine T and B lymphoma cell lines: involvement of reactive oxygen species, Ca(2+) homeostasis, and cytokine gene expression. Toxicol. In Vitro. 2003;17:385–395
  33. Kim SH, Sharma RP. Mercury-induced apoptosis and necrosis in murine macrophages: role of calcium-induced reactive oxygen species and p38 mitogen-activated protein kinase signaling. Toxicol. Appl. Pharmacol. 2004;196:47–57
  34. Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. U. S. A. 1994;91:7355–7359
  35. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996;19:312–318
  36. Kunimoto M. Methylmercury induces apoptosis of rat cerebellar neurons in primary culture. Biochem. Biophys. Res. Commun. 1994;204:310–317
  37. Kuo TC, Lin-Shiau SY. Early acute necrosis and delayed apoptosis induced by methyl mercury in murine peritoneal neutrophils. Basic Clin. Pharmacol. Toxicol. 2004;94:274–281
  38. LeBel CP, Ali SF, Bondy SC. Deferoxamine inhibits methyl mercury-induced increases in reactive oxygen species formation in rat brain. Toxicol. Appl. Pharmacol. 1992;112:161–165
  39. Lee SC, Liu W, Dickson DW, Brosnan CF, Berman JW. Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J. Immunol. 1993;150:2659–2667
  40. Limke TL, Atchison WD. Acute exposure to methylmercury opens the mitochondrial permeability transition pore in rat cerebellar granule cells. Toxicol. Appl. Pharmacol. 2002;178:52–61
  41. Ling EA, Wong WC. The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia. 1993;7:9–18
  42. Loddick SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J. Cereb. Blood Flow Metab. 1998;18:176–179
  43. Meda L, Cassatella MA, Szendrei GI, Otvos L, Baron P, Villalba M, et al. Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature. 1995;374:647–650
  44. Mundy WR, Freudenrich TM. Sensitivity of immature neurons in culture to metal-induced changes in reactive oxygen species and intracellular free calcium. Neurotoxicology. 2000;21:1135–1144
  45. Nencioni A, Lauber K, Grunebach F, Brugger W, Denzlinger C, Wesselborg S, et al. Cyclopentenone prostaglandins induce caspase activation and apoptosis in dendritic cells by a PPAR-gamma-independent mechanism: regulation by inflammatory and T cell-derived stimuli. Exp. Hematol. 2002;30:1020–1028
  46. Nishioku T, Takai N, Miyamoto K, Murao K, Hara C, Yamamoto K, et al. Involvement of caspase 3-like protease in methylmercury-induced apoptosis of primary cultured rat cerebral microglia. Brain Res. 2000;871:160–164
  47. Olivieri G, Brack C, Muller-Spahn F, Stahelin HB, Herrmann M, Renard P, et al. Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells. J. Neurochem. 2000;74:231–236
  48. Pedersen MB, Hansen JC, Mulvad G, Pedersen HS, Gregersen M, Danscher G. Mercury accumulations in brains from populations exposed to high and low dietary levels of methyl mercury. Concentration, chemical form and distribution of mercury in brain samples from autopsies. Int. J. Circumpolar Health. 1999;58:96–107
  49. Qiu Z, Gruol DL. Interleukin-6, beta-amyloid peptide and NMDA interactions in rat cortical neurons. J. Neuroimmunol. 2003;139:51–57
  50. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998;391:79–82
  51. Risher JF, Murray HE, Prince GR. Organic mercury compounds: human exposure and its relevance to public health. Toxicol. Ind. Health. 2002;18:109–160
  52. Sanchez RN, Chan CK, Garg S, Kwong JM, Wong MJ, Sadun AA, et al. Interleukin-6 in retinal ischemia reperfusion injury in rats. Invest. Ophthalmol. Visual Sci. 2003;44:4006–4011
  53. Scanlon JM, Reynolds IJ. Effects of oxidants and glutamate receptor activation on mitochondrial membrane potential in rat forebrain neurons. J. Neurochem. 1998;71:2392–2400
  54. Schuster PF, Krabbenhoft DP, Naftz DL, Cecil LD, Olson ML, Dewild JF, et al. Atmospheric mercury deposition during the last 270 years: a glacial ice core record of natural and anthropogenic sources. Environ. Sci. Technol. 2002;36:2303–2310
  55. Shanker G, Aschner M. Methylmercury-induced reactive oxygen species formation in neonatal cerebral astrocytic cultures is attenuated by antioxidants. Brain Res. Mol. Brain Res. 2003;110:85–91
  56. Shenker BJ, Guo TL, Shapiro IM. Low-level methylmercury exposure causes human T-cells to undergo apoptosis: evidence of mitochondrial dysfunction. Environ. Res. 1998;77:149–159
  57. Sone N, Larsstuvold MK, Kagawa Y. Effect of methyl mercury on phosphorylation, transport, and oxidation in mammalian mitochondria. J. Biochem. 1977;82:859–868
  58. Tampo Y, Kotamraju S, Chitambar CR, Kalivendi SV, Keszler A, Joseph J, et al. Oxidative stress-induced iron signaling is responsible for peroxide-dependent oxidation of dichlorodihydrofluorescein in endothelial cells: role of transferrin receptor-dependent iron uptake in apoptosis. Circ. Res. 2003;92:56–63
  59. Vaidya S, Somers EP, Wright SD, Detmers PA, Bansal VS. 15-Deoxy-Delta12,1412,14-prostaglandin J2 inhibits the beta2 integrin-dependent oxidative burst: involvement of a mechanism distinct from peroxisome proliferator-activated receptor gamma ligation. J. Immunol. 1999;163:6187–6192
  60. Willson TM, Cobb JE, Cowan DJ, Wiethe RW, Correa ID, Prakash SR, et al. The structure–activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J. Med. Chem. 1996;39:665–668
  61. Yan LJ, Levine RL, Sohal RS. Oxidative damage during aging targets mitochondrial aconitase. Proc. Natl. Acad. Sci. U. S. A. 1997;94:11168–11172
  62. Ye JM, Doyle PJ, Iglesias MA, Watson DG, Cooney GJ, Kraegen EW. Peroxisome proliferator-activated receptor (PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats: comparison with PPAR-gamma activation. Diabetes. 2001;50:411–417
  63. Yee S, Choi BH. Oxidative stress in neurotoxic effects of methylmercury poisoning. Neurotoxicology. 1996;17:17–26
  64. Zhang J, Fu M, Zhao L, Chen YE. 15-Deoxy-prostaglandin J(2) inhibits PDGF-A and -B chain expression in human vascular endothelial cells independent of PPAR gamma. Biochem. Biophys. Res. Commun. 2002;298:128–132

PII: S0165-5728(05)00412-1

doi: 10.1016/j.jneuroim.2005.09.007

Journal of Neuroimmunology
Volume 171, Issue 1 , Pages 17-28 , February 2006