The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

cAMP/PKA Agonist Restores the Fasting-Induced Down-Regulation of nNOS Expression in the Paraventricular Nucleus

  • Yoo, Sang-Bae (Dental Research Institute, Department of Oral & Maxillofacial Surgery, Seoul National University School of Dentistry) ;
  • Lee, Seoul (Department of Pharmacology, Wonkwang University School of Medicine) ;
  • Lee, Joo-Young (Dental Research Institute, Department of Oral & Maxillofacial Surgery, Seoul National University School of Dentistry) ;
  • Kim, Bom-Taeck (Department of Family Practice and Community Health, Ajou University School of Medicine) ;
  • Lee, Jong-Ho (Dental Research Institute, Department of Oral & Maxillofacial Surgery, Seoul National University School of Dentistry) ;
  • Jahng, Jeong-Won (Dental Research Institute, Department of Oral & Maxillofacial Surgery, Seoul National University School of Dentistry)
  • Received : 2012.06.04
  • Accepted : 2012.08.21
  • Published : 2012.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Gene expression of neuronal nitric oxide synthase (nNOS) changes in the hypothalamic paraventricular nucleus (PVN) depending on feeding conditions, which is decreased during food deprivation and restored by refeeding, and phosphorylated cAMP response element binding protein (pCREB) was suggested to play a role in its regulation. This study was conducted to examine if the fasting-induced down-regulation of the PVN-nNOS expression is restored by activation of cAMP-dependent protein kinase A (cAMP/PKA) pathway. Freely moving rats received intracerebroventricular (icv) injection of cAMP/PKA activator Sp-cAMP (40 nmol) or vehicle (sterilized saline) following 48 h of food deprivation. One hour after drug injections, rats were transcardially perfused with 4% paraformaldehyde, and the PVN tissues were processed for nNOS or pCREB immunohistochemistry. Sp-cAMP significantly increased not only nNOS but also pCREB immunoreactivities in the PVN of food deprived rats. Fastinginduced down-regulation of the PVN-nNOS was restored by 1 h after the icv Sp-cAMP. Results suggest that cAMP/PKA pathway may mediate the regulation of the PVN-nNOS expression depending on different feeding conditions.

Keywords

References

  1. Ueta Y, Levy A, Chowdrey HS, Lightman SL. Inhibition of hypothalamic nitric oxide synthase gene expression in the rat paraventricular nucleus by food deprivation is independent of serotonin depletion. J Neuroendocrinol. 1995;7:861-865. https://doi.org/10.1111/j.1365-2826.1995.tb00727.x
  2. O'Shea RD, Gundlach AL. Food or water deprivation modulate nitric oxide synthase (NOS) activity and gene expression in rat hypothalamic neurones: correlation with neurosecretory activity? J Neuroendocrinol. 1996;8:417-425. https://doi.org/10.1046/j.1365-2826.1996.04682.x
  3. Kim YM, Lee JY, Choi SH, Kim DG, Jahng JW. RU486 blocks fasting-induced decrease of neuronal nitric oxide synthase in the rat paraventricular nucleus. Brain Res. 2004;1018:221-226. https://doi.org/10.1016/j.brainres.2004.05.068
  4. Jahng JW, Lee JH, Kim GT, Kim YM, Houpt TA, Kim DG. Adrenalectomy abolishes fasting-induced down-regulation of NADPH-diaphorase in the rat paraventricular nucleus. Yonsei Med J. 2004;45:123-128. https://doi.org/10.3349/ymj.2004.45.1.123
  5. Jahng JW, Lee JY, Yoo SB, Kim YM, Ryu V, Kang DW, Lee JH. Refeeding-induced expression of neuronal nitric oxide synthase in the rat paraventricular nucleus. Brain Res. 2005;1048:185-192. https://doi.org/10.1016/j.brainres.2005.04.072
  6. van Haasteren GA, Linkels E, van Toor H, Klootwijk W, Kaptein E, de Jong FH, Reymond MJ, Visser TJ, de Greef WJ. Effects of long-term food reduction on the hypothalamus-pituitary- thyroid axis in male and female rats. J Endocrinol. 1996; 150:169-178. https://doi.org/10.1677/joe.0.1500169
  7. Yoshihara T, Honma S, Katsuno Y, Honma K. Dissociation of paraventricular NPY release and plasma corticosterone levels in rats under food deprivation. Am J Physiol. 1996;271:E239-245.
  8. Lee JY, Kang DW, Kim DG, Jahng JW. Fasting-induced downregulation of NADPH-diaphorase in the magnocellular PVN of rats. Yonsei Med J. 2004;45:917-922. https://doi.org/10.3349/ymj.2004.45.5.917
  9. Jeong Y, Won J, Kim C, Yim J. 5'-Flanking sequence and promoter activity of the rabbit neuronal nitric oxide synthase (nNOS) gene. Mol Cells. 2000;10:566-574. https://doi.org/10.1007/s10059-000-0566-7
  10. Rife TK, Xie J, Redman C, Young AP. The 5'2 promoter of the neuronal nitric oxide synthase dual promoter complex mediates inducibility by nerve growth factor. Brain Res Mol Brain Res. 2000;75:225-236. https://doi.org/10.1016/S0169-328X(99)00293-4
  11. Sasaki M, Gonzalez-Zulueta M, Huang H, Herring WJ, Ahn S, Ginty DD, Dawson VL, Dawson TM. Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism. Proc Natl Acad Sci USA. 2000;97:8617-8622. https://doi.org/10.1073/pnas.97.15.8617
  12. Gonzalez GA, Montminy MR. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 1989;59:675-680. https://doi.org/10.1016/0092-8674(89)90013-5
  13. Son GH, Geum D, Jung H, Kim K. Glucocorticoid inhibits growth factor-induced differentiation of hippocampal progenitor HiB5 cells. J Neurochem. 2001;79:1013-1021.
  14. Lee JY, Lee JH, Kim DG, Jahng JW. Dexamethasone blocks the refeeding-induced phosphorylation of cAMP response element- binding protein in the rat hypothalamus. Neurosci Lett. 2003;344:107-111. https://doi.org/10.1016/S0304-3940(03)00299-4
  15. Timofeeva E, Picard F, Duclos M, Deshaies Y, Richard D. Neuronal activation and corticotropin-releasing hormone expression in the brain of obese (fa/fa) and lean (fa/?) Zucker rats in response to refeeding. Eur J Neurosci. 2002;15:1013-1029. https://doi.org/10.1046/j.1460-9568.2002.01942.x
  16. Sheriff S, Chance WT, Iqbal S, Rizvi TA, Xiao C, Kasckow JW, Balasubramaniam A. Hypothalamic administration of cAMP agonist/PKA activator inhibits both schedule feeding and NPYinduced feeding in rats. Peptides. 2003;24:245-254. https://doi.org/10.1016/S0196-9781(03)00037-8
  17. Jahng JW, Spencer CM, Choi SH, Kim DG, Houpt TA. Nitric oxide is involved in lithium-induced immediate early gene expressions in the adrenal medulla. Eur J Pharmacol. 2004; 489:111-116. https://doi.org/10.1016/j.ejphar.2004.02.035
  18. Spencer CM, Jahng JW, Ryu V, Houpt TA. Lithium-induced gene expression of inducible cyclic adenosine monophosphate early repressor in the rat adrenal gland. J Neurosci Res. 2005;82:273-282. https://doi.org/10.1002/jnr.20617
  19. Lee JH, Cha MJ, Yoo SB, Moon YW, Noh SJ, Jahng JW. Leptin blocks the fasting-induced increase of pERK1/2 in the paraventricular nucleus of rats. Regul Pept. 2010;162:122-128. https://doi.org/10.1016/j.regpep.2010.03.001
  20. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Academic Press; 1986.
  21. Jahng JW, Houpt TA, Kim SJ, Joh TH, Son JH. Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice. Brain Res. 1998;790:67-73. https://doi.org/10.1016/S0006-8993(98)00049-3
  22. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382:250-252. https://doi.org/10.1038/382250a0
  23. Boissel JP, Bros M, Schröck A, Gödtel-Armbrust U, Förstermann U. Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the level of bioactive NO production: analysis of the signaling mechanisms that are involved. Biochemistry. 2004;43:7197-7206. https://doi.org/10.1021/bi0302191
  24. Eberhardt W, Engels C, Müller R, Pfeilschifter J. Mechanisms of dexamethasone-mediated inhibition of cAMP-induced tPA expression in rat mesangial cells. Kidney Int. 2002;62:809-821. https://doi.org/10.1046/j.1523-1755.2002.00538.x
  25. Dostmann WR, Taylor SS, Genieser HG, Jastorff B, Doskeland SO, Ogreid D. Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3',5'-cyclic phosphorothioates. J Biol Chem. 1990; 265:10484-10491.
  26. Wu G, Meininger CJ. Regulation of nitric oxide synthesis by dietary factors. Annu Rev Nutr. 2002;22:61-86. https://doi.org/10.1146/annurev.nutr.22.110901.145329
  27. Park SH, Lee YJ, Lim MJ, Kim EJ, Lee JH, Han HJ. High glucose inhibits fructose uptake in renal proximal tubule cells: involvement of cAMP, PLC/PKC, p44/42 MAPK, and cPLA2. J Cell Physiol. 2004;200:407-416. https://doi.org/10.1002/jcp.20023
  28. Santangelo GM. Glucose signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 2006;70:253-282. https://doi.org/10.1128/MMBR.70.1.253-282.2006
  29. Otsubo H, Kondoh T, Shibata M, Torii K, Ueta Y. Induction of Fos expression in the rat forebrain after intragastric administration of monosodium L-glutamate, glucose and NaCl. Neuroscience. 2011;196:97-103. https://doi.org/10.1016/j.neuroscience.2011.09.003
  30. Bredt DS, Snyder SH. Nitric oxide, a novel neuronal messenger. Neuron. 1992;8:3-11. https://doi.org/10.1016/0896-6273(92)90104-L
  31. Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Annu Rev Physiol. 1995;57:683-706. https://doi.org/10.1146/annurev.ph.57.030195.003343
  32. Yun HY, Dawson VL, Dawson TM. Neurobiology of nitric oxide. Crit Rev Neurobiol. 1996;10:291-316. https://doi.org/10.1615/CritRevNeurobiol.v10.i3-4.20
  33. Boissel JP, Schwarz PM, Förstermann U. Neuronal-type NO synthase: transcript diversity and expressional regulation. Nitric Oxide. 1998;2:337-349. https://doi.org/10.1006/niox.1998.0189
  34. Dawson TM, Snyder SH. Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J Neurosci. 1994;14: 5147-5159.
  35. Förstermann U, Boissel JP, Kleinert H. Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J. 1998;12:773-790. https://doi.org/10.1096/fasebj.12.10.773
  36. Casto RM, VanNess JM, Overton JM. Effects of central leptin administration on blood pressure in normotensive rats. Neurosci Lett. 1998;246:29-32. https://doi.org/10.1016/S0304-3940(98)00223-7
  37. Krukoff TL. Central actions of nitric oxide in regulation of autonomic functions. Brain Res Brain Res Rev. 1999;30:52-65. https://doi.org/10.1016/S0165-0173(99)00010-7
  38. Stern JE, Li Y, Zhang W. Nitric oxide: a local signalling molecule controlling the activity of pre-autonomic neurones in the paraventricular nucleus of the hypothalamus. Acta Physiol Scand. 2003;177:37-42. https://doi.org/10.1046/j.1365-201X.2003.01045.x
  39. Kadowaki K, Kishimoto J, Leng G, Emson PC. Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS activity in the rat hypothalamo-hypophysial system after chronic salt loading: evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion. Endocrinology. 1994;134:1011-1017. https://doi.org/10.1210/en.134.3.1011
  40. Swanson LW, Sawchenko PE. Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annu Rev Neurosci. 1983;6:269-324. https://doi.org/10.1146/annurev.ne.06.030183.001413
  41. Burlet AJ, Jhanwar-Uniyal M, Chapleur-Chateau M, Burlet CR, Leibowitz SF. Effect of food deprivation and refeeding on the concentration of vasopressin and oxytocin in discrete hypothalamic sites. Pharmacol Biochem Behav. 1992;43:897-905. https://doi.org/10.1016/0091-3057(92)90423-D