The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Effects of PCB Congeners in Rodent Neuronal Cells in Culture

  • Kim, Sun-Young (Department of Pharmacology, School of Medicine, Catholic University of Daegu) ;
  • Yang, Jae-Ho (Department of Pharmacology, School of Medicine, Catholic University of Daegu)
  • Published : 2005.02.21
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Abstract

We attempted to analyze the mechanism of polychlorinated biphenyl (PCB)-induced neurotoxicity and identify the target molecules in the neuronal cells for PCBs.Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old Sprague Dawley (SD) rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. Only non-coplanar PCBs at a high dose showed a significant increase of total protein kinase C (PKC) activity at phobol 12,13-dibutyrate ([$^3M$]PDBu) binding assay, indicating that non-coplanar PCBs are more neuroactive than coplanar PCBs in neuronal cells. PKC isozymes were immunoblotted with the selected monoclonal antibodies. PKC-${\alpha}$, ${\delta}$, and ε were activated with non-coplanar PCB exposure. Receptor for activated C kinase-1 (RACK-1), anchoring protein for activated PKC, was more induced with exposure to coplanar PCBs than non-coplanar PCBs. Reverse transcription PCR (RT-PCR) analysis showed induction of neurogranin (RC-3) and growth associated protein-43 (GAP-43) mRNA with non-coplanar PCBs. The results indicate that these factors may be useful biomarkers for differentiating non-coplanar PCBs from coplanar PCBs. The present study demonstrated that non-coplanar PCBs are more neuroactive congeners than coplanar PCBs.

Keywords

References

  1. Amos S, Martin PM, Polar GA, Parsons SJ, Hussaini IM. Phorbol 12-myristate 13-acetate induces epidermal growth factor receptor transactivation via protein kinase C delta/c-Src pathways in glioblastoma cells. J Biol Chem In Press, 2004
  2. Bendotti S, Baldessari R, Samanin S, Biasi SD. Ultrastructural immunolocalization of GAP-43 in the sprouted mossy fibres of kainic acid lesioned rats. Neuroreport 5: 2645-2648, 1994 https://doi.org/10.1097/00001756-199412000-00060
  3. Casoli T, Stefano GD, Fattoretti P, Solazzi M, Delfino A, Biagini G, Bertoni-Freddari C. GAP-43 mRNA detection by in situ hybridization, direct and indirect in situ RT-PCR in hippocampal and cerebellar tissue sections of adult rat brain. Micron 34: 415-422, 2003 https://doi.org/10.1016/S0968-4328(03)00038-6
  4. Chen C, Kano M, Abeliovich A, Chan L, Bos S, Kim JJ, Hachimoto K, Thompson RF, Tonegawa S. Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKC-$\gamma$ mutant mice. Cell 83: 1233-1242, 1995 https://doi.org/10.1016/0092-8674(95)90148-5
  5. Csukai M, Mochly-Rosen D. Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localization. Pharmacol Res 39: 253-259, 1999 https://doi.org/10.1006/phrs.1998.0418
  6. Disatnik MH, Buraggi G, Mochly-Rosen D. Localization of protein kinase C isozymes in cardiac myocytes. Exp Cell Res 210: 287- 297, 1994 https://doi.org/10.1006/excr.1994.1041
  7. Guizzetti M, Wei M, Costa LG. The role of protein kinase C-$\alpha$ and -$\varepsilon$ isozymes in DNA synthesis induced by muscarinic receptors in a glial cell line. Eur J Pharmacol 359: 223-233, 1998 https://doi.org/10.1016/S0014-2999(98)00620-7
  8. Hama T, Huang KP, Guroff G. Protein kinase C as a component of a nerve growth factor-sensitive phosphorylation system in PC 12 cells. Proc Natl Acad Sci USA 83: 2353-2357, 1986 https://doi.org/10.1073/pnas.83.8.2353
  9. Herreo I, Miras-Portugal MT, Sanshez-prieto J. Positive feedback of glutamate exocytosis by metabotrophic presynaptic receptor stimulation. Nature 360: 163-166, 1992 https://doi.org/10.1038/360163a0
  10. Jacobson JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Eng J Med 335: 783-789, 1996 https://doi.org/10.1056/NEJM199609123351104
  11. Kodavanti PRS, Ward TR, Shin D, Tilson HA, Harry GJ. Comparative effects of two polychlorinated biphenyl congeners on calcium homeostasis in rat cerebellar granule cells. Toxicol Appl Pharmacol 123: 97-106, 1993 https://doi.org/10.1006/taap.1993.1226
  12. Kodavanti PRS, Shafer TJ, Ward TR, Mundy WR, Freundrich T, Harry GJ, Tilson HA. Differential effects of polychlorinated biphenyl congeners on phosphoinositide hydrolysis and protein kinase C translocation in rat cerebellar granule cells. Brain Res 662: 75-82, 1994 https://doi.org/10.1016/0006-8993(94)90797-8
  13. Kodavanti PRS, Ward TR, McKinney JD, Waller CL, Tilson HA. Increased $[^3H]$phorbol ester binding in rat cerebellar granule cells and inhibition of $^{45}Ca^{2+}$ sequestration in rat cerebellum by polychlorinated diphenyl ether congeners and analogs: structure-activity relationships. Toxicol Appl Pharmacol 138: 251-256, 1996 https://doi.org/10.1006/taap.1996.0123
  14. Konno Y, Ohno S, Akita Y, Kawasaki H, Suzuki S. Enzymatic properties of a novel phorbol ester receptor/ protein kinase nPKC. J Biochem (Tokyo) 106: 673-678, 1989 https://doi.org/10.1093/oxfordjournals.jbchem.a122915
  15. Latchoumycandane C, Anantharam V, Kitazawa M, Yang Y, Kanthamy A, Kanthasamy AG. Protein kinase C delta (PKC {delta}) is a key downstream mediator of manganese-induced apoptosis in dopaminergic neuronal cells. J Pharmacol Exp Ther In Press, 2004
  16. Manji HK, Etcheberrigaray R, Chen G, Olds JL. Lithium decreases membrane-associated protein kinase C in hippocampus: Sensitivity for the alpha isozyme. J Neurochem 61: 2303-2310, 1993 https://doi.org/10.1111/j.1471-4159.1993.tb07474.x
  17. Mariussen E, Myhre O, Reistad T, Fonnum F. The polychlorinated Biphenyl Mixture Aroclor 1254 induces death of rat cerevellar granule cells: The involvement of the N-methyl-D-aspartate receptor and reactive oxygen species. Toxicol Appl Pharmacol 179: 137-144, 2002 https://doi.org/10.1006/taap.2002.9353
  18. Matsushima H, Shimohama S, Chachin M, Taniguchi T, Kimura J. $Ca^{2+}$-dependent and $Ca^{2+}$-independent protein Kinase C changes in the brain of patients with Alzheimer's disease. J Neurochem 67: 317-323, 1996 https://doi.org/10.1046/j.1471-4159.1996.67010317.x
  19. Meiri KF, Willard M, Johnson MI. Distribution and phosphorylation of the growth associated protein GAP-43 in regenerating sympathetic neurons in culture. J Neurosci 8: 2571-2581, 1988
  20. Molchan SE, Sunderland T, McIntosh AR, Herscovitch P, Schreurs DG. A functional anatomical study of associative learning in humans. Proc Natl Acad Sci USA 91: 8122-8126, 1994 https://doi.org/10.1073/pnas.91.17.8122
  21. Nishizuka Y. The molecular heterogenicity of protein kinase C and its implication in cellular regulation. Nature 334: 661-665, 1988 https://doi.org/10.1038/334661a0
  22. Olivero J, Ganey PE. Role of protein phosphorylation in activation of phospholipase $A_2 by the polychlorinated biphenyl mixture Aroclor 1242. Toxicol Appl Pharmacol 161: 9-16, 2000
  23. Pasinelli S, Ramakers GMJ, Urban IJA, Hens JJH, Oestreicher AB, Graan PNDE, Gispen WH. Long-term potentiation and synaptic protein phosphorylation. Behavioural Brain Res 66: 53-59, 1995 https://doi.org/10.1016/0166-4328(94)00124-X
  24. Riedel G. Protein kinase C: A memory kinase? Prog Neuropsychopharmacol Biol Psychiat 21: 373-378, 1997 https://doi.org/10.1192/pb.21.6.373
  25. Ron D, Jiang Z, Yao l, Vagts A, Diamond I, Gordon A. Coordinated movement of RACK1 with activated betaIIPKC. J Biol Chem 274: 27039-27046, 1999 https://doi.org/10.1074/jbc.274.38.27039
  26. Saito N, Itouji A, Totani Y, Osawa I, Koide H, Fujisawa N, Ogita K, Tanaka C. Cellular and intracellular localization of epsilonsubspecies of protein kinase C in the rat brain: presynaptic localization of the epsilon-subspecies. Brain Res 607: 214-248, 1993
  27. Schantz SL, Moshtaghian J, Ness DK. Spatial learning deficits in adult rats exposed to ortho-substituted PCB congeners during gestation and lactation. Fundam Appl Toxicol 26: 117-126, 1995
  28. Schechtman D, Mochly-Rosen D. Adaptor proteins in protein kinase C-mediated signal transduction. Oncogene 20: 6339-6347, 2001 https://doi.org/10.1038/sj.onc.1204778
  29. Sharif TR, Sharif M. Overexpression of protein kinase C-$\epsilon$ in astroglial brain tumor derived cell lines and primary tumor samples. Int J Oncol 15: 237-243, 1999
  30. Son H, Madelian V, Carpenter DO. The translocation and involvement of protein kinase C in mossy fiber-CA3 long-term potentiation in hippocampus of the rat brain. Brain Res 739: 282-292, 1996 https://doi.org/10.1016/S0006-8993(96)00836-0
  31. Swanson GM, Ratcliffe HE, Fischer LJ. Human exposures to polychlorinated biphenyls (PCBs): A critical assessment of the evidence for adverse health effects. Regul Toxicol Pharmacol 21: 136-150, 1995 https://doi.org/10.1006/rtph.1995.1018
  32. Vaccarino FM, Liliequist S, Tallman JF. Modulation of protein kinase C translocation by excitatory and inhibitory amino acids in primary cultures of neurons. J Neurochem 57: 391-396, 1991 https://doi.org/10.1111/j.1471-4159.1991.tb03765.x
  33. Yang JH, Vogel C, Abel J. A malignant transformation of human cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibits altered expressions of growth regulatory factors. Carcinogenesis 21: 5-12, 1999
  34. Yang JH. Expression of dioxin-responsive genes in human endometrial cells in culture. Biochem Biophys Res Commun 257: 259-263, 1999 https://doi.org/10.1006/bbrc.1999.0451
  35. Yang JH, Derr-Yellin EC, Kodavanti PRS. Alterations in brain protein kinase C isoforms following developmental exposure to a polychlorinated biphenyl mixture. Mol Brain Res 111: 123-135, 2003 https://doi.org/10.1016/S0169-328X(02)00697-6