Identification of Differentially Expressed Genes in Murine Hippocampus by Modulation of Nitric Oxide in Kainic Acid-induced Neurotoxic Animal Model

  • Suh, Yo-Ahn (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kwon, O-Min (Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University) ;
  • Yim, So-Young (Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University) ;
  • Lee, Hee-Jae (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University)
  • Published : 2007.08.31

Abstract

Kainic acid (KA) causes neurodegeneration, but no consensus has been reached concerning its mechanism. Nitric oxide may be a regulator of the mechanism. We identified differentially expressed genes in the hippocampus of mice treated with kainic acid, together with or without L-NAME, a nonselective nitric oxide synthase inhibitor, using a new differential display PCR method based on annealing control primers. Eight genes were identified, including clathrin light polypeptide, TATA element modulatory factor 1, neurexin III, ND4, ATPase, $H^+$ transporting, V1 subunit E isoform 1, and N-myc downstream regulated gene 2. Although the functions of these genes and their products remain to be determined, their identification provides insight into the molecular mechanism(s) involved in KA-induced neuronal cell death in the hippocampal CA3 area.

Keywords

References

  1. Almeida A, Almeida J, Bolanos JP, Moncada S. Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci USA 98: 15294-15299, 2001
  2. Ben-Ari Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal loop epilepsy. Neuroscience 14: 375-403, 1985 https://doi.org/10.1016/0306-4522(85)90299-4
  3. Brookes PS, Salinas EP, Darley-Usmar K, Eiserich JP, Freeman BA, Darley-Usmar VM, Anderson PG. Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release. J Biol Chem 275: 20474-20479, 2000 https://doi.org/10.1074/jbc.M001077200
  4. Brown GC, Borutaite V. Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Radic Biol Med 33: 1440-1450, 2002 https://doi.org/10.1016/S0891-5849(02)01112-7
  5. Chung HT, Pae HO, Choi BM, Billiar TR, Kim YM. Nitric oxide as bioregulator of apoptosis. Biochem Biophys Res Commun 282: 1075-1079, 2001 https://doi.org/10.1006/bbrc.2001.4670
  6. Ciani E, Guidi S, Della Valle G, Perini G, Bartesaghi R, Contestabile A. Nitric oxide protects neuroblastoma cells from apoptosis induced by serum deprivation through cAMP-response element-binding protein (CREB) activation. J Biol Chem 277: 49896-49902, 2002 https://doi.org/10.1074/jbc.M206177200
  7. Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au W, Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung H, Leung S, Lin MC. N-myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer 106: 342-347, 2003 https://doi.org/10.1002/ijc.11228
  8. Ferrer I, Martin F, Serrano T, Reiriz J, Perez-Navarro E, Alberch J, Macaya A, Plana AM. Both apoptosis and necrosis occur following intrastriata administration of excitotxins. Acta Neuropathol 90: 504-510, 1995 https://doi.org/10.1007/BF00294812
  9. Hao W, Myhre AP, Palmer JP. Nitric oxide mediates IL-1beta stimulation of heat shock protein but not IL-1beta inhibition of glutamic acid decarboxylase. Autoimmunity 29: 93-101, 1999 https://doi.org/10.3109/08916939908995378
  10. Harry GJ, Sills R, Schlosser MJ, Maier WE. Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME). Neurtoxicity Res 3: 307-319, 2001 https://doi.org/10.1007/BF03033270
  11. Hu X, Liu X, Deng Y, Lin S, Wu L, Zhang J, Wang L, Wang X, Li X, Shen L, Zhang Y, Yao L. Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues. Cell Tissue Res 325: 67-76, 2006 https://doi.org/10.1007/s00441-005-0137-5
  12. Hwang IT, Kim YJ, Kim SH, Kwak CI, Gu YY, Chun JY. Annealing control primer system for improving specificity of PCR amplification. Biotechniques 35:1180-1184, 2003
  13. Kim YJ, Kwak CI, Gu YY, Hwang IT, Chun JY. Annealing control primer system for identification of differentially expressed genes on agarose gels. Biotechniques 36: 424-426, 2004
  14. Kim YM, Talanian RV, Li J, Billiar TR. Nitric oxide prevents IL-1 beta and IFN-gamma-inducing factor (IL-18) release from macrophages by inhibiting caspase-1. J Immunol 161: 4122-4128, 1998
  15. Laursen SE, Belknap JK. Intracerebroventricular injections in mice. Some methodological refinements. J Pharmacol Methods 16: 355-357, 1986 https://doi.org/10.1016/0160-5402(86)90038-0
  16. Mannick JB, Hausladen A, Liu L, Hess DT, Zeng M, Mia QX, Kane LS, Gow AJ, Stamler JS. Fas-induced caspase denitrosylation. Science 284: 651-654, 1999 https://doi.org/10.1126/science.284.5414.651
  17. Moncada C, Lekieffre D, Arvin B, Meldrum B. Effect of NO synthase inhibition on NMDA- and ischemia-induced hippocampal region. Neuro Report 3: 530-532, 1992
  18. Murray J, Campbell D, Morrice N, Auld GC, Shpiro N, Marquez R, Peggie M, Bain J, Bloomberg GB, Grahammer F, Lang F, Wulff P, Kuhl D, Cohen P. Exploitation of KESTREL to identify NDRG2 family members as physiological substrates for SGK1 and GSK3. Biochem J 384: 477-488, 2004 https://doi.org/10.1042/BJ20041057
  19. Nichols NR. Ndrg2, a novel gene regulated by glucocorticoids and antidepressants, is highly expressed in astrocytes. Ann N Y Acad Sci 1007: 349-356, 2003 https://doi.org/10.1196/annals.1286.034
  20. Phelps S, Mitchell J, Wheal HV. Changes to synaptic ultrastructure in field CA1 of the rat hippocampus following intracerebroventricular injection of kainic acid. Neuroscience 40: 687-699, 1991 https://doi.org/10.1016/0306-4522(91)90005-9
  21. Simonian NA, Getz RL, Leveque JC, Konradi C, Coyle JT. Kainic acid induces apoptosis in neurons. Neuroscience 75: 1047-1055, 1996 https://doi.org/10.1016/0306-4522(96)00326-0
  22. Sperk G, Lassmann H, Baran H, Seitelberger F, Hornykiewicz O. Kainic acid induced seizures: dose relationship of behavioral, neurochemical and histopathological changes. Brain Res 328: 289-285, 1985
  23. Tanaka T, Tanaka S, Fujita T, Takano K, Fukuda H, Sako K, Yonemasu Y. Experimental complex partial seizures induced by a microinjection of kainic acid into limbic structures. Prog Neurobiol 38: 317-334, 1992 https://doi.org/10.1016/0301-0082(92)90023-8
  24. Tauck DL, Nadler JV. Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid treated rats. J Neurosci 5: 1016-1022, 1985 https://doi.org/10.1523/JNEUROSCI.05-04-01016.1985
  25. Tremblay E, Ottersen OP, Rovira C, Ben-Ari Y. Intra-amygdaloid injections of kainic acid: regional metabolic changes and their relation to the pathological alterations. Neuroscience 8: 299- 315, 1983 https://doi.org/10.1016/0306-4522(83)90068-4
  26. Zhang J, Li F, Liu X, Shen L, Liu J, Su J, Zhang W, Deng Y, Wang L, Liu N, Han W, Zhang J, Ji S, Yang A, Han H, Yao L. The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter. J Biol Chem 281: 39159-39168, 2006 https://doi.org/10.1074/jbc.M605820200