Enhancement of tyrosine hydroxylase expression by Cordyceps militaris

Kumar Sapkota 1 , Seung Kim, Young Park 3 , Bong-Suk Choi, Se-Eun Park and Sung-Jun Kim
  • 1 Department of Biotechnology, Chosun University, Gwangju, 501-759, Republic of Korea
  • 2 BK21 Research Team for Protein Activity Control, Chosun University, Gwangju, 501-759, Republic of Korea
  • 3 Cancer Research Center, Hwasun Hospital, Chonnam National University, Jeonnam, 519-809, Republic of Korea
  • 4 Department of Alternative medicine, Gwangju University, Gwangju, 503-703, Republic of Korea

Abstract

Cordyceps militaris is a popular medicinal mushroom, and has received extensive attention for medical application because of its various physiological activities. However, there is limited information about the function of Cordyceps militaris on dopaminergic system. This study has attempted to evaluate the effect of cultured fruiting bodies of Cordyceps militaris extract (CME) on the expression of the tyrosine hydroxylase (TH) gene in PC12 cells and rat brain and stomach. Related mRNA levels were determined by the RT-PCR. Protein levels were measured by Western blot and immunohistochemistry. Our results demonstrated CME induced TH gene expression both in vitro and in vivo. Treatment of 10 µg/ml and 20 mg/kg CME to PC12 cells and rat cells yielded significant increases of TH protein levels. Significantly, TH immunoreactive neurons were detected not only in the brain but also in the stomach. TH-immunohistochemical staining was markedly enhanced in animals treated with CME compared to those in the untreated control. These results suggest that CME can upregulate the dopaminergic (DArgic) system, and may contribute to neuroprotection in neurodegenerative diseases.

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  • [1] Nagatsu T., Levitt M., Undenfriend S., Tyrosine hydroxylase, the initial step in norepinephrine biosynthesis, J. Biol. Chem., 1964, 239, 2910–2917

  • [2] Nakashima A., Hayashi N., Kaneko Y.S., Mori K., Sabban E.L., Nagatsu T., et al., Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines, J. Neural. Transm., 2009, 116, 1355–1362 http://dx.doi.org/10.1007/s00702-009-0227-8

  • [3] Moore D.J., West A.B., Dawson V.L., Dawson T.M., Molecular pathophysiology of Parkinson’s disease, Annu. Rev. Neurosci., 2005, 28, 57–87 http://dx.doi.org/10.1146/annurev.neuro.28.061604.135718

  • [4] Von Bohlen und Halbach O., Schober A., Krieglstein K., Genes, proteins, and neurotoxins involved in Parkinson’s disease, Prog. Neurobiol., 2004, 73, 151–177 http://dx.doi.org/10.1016/j.pneurobio.2004.05.002

  • [5] Manyam B.V., Dhanasekaran M., Hare T.A., Neuroprotective effects of the antiparkinson drug Mucuna pruriens., Phytother. Res., 2004, 18, 706–712 http://dx.doi.org/10.1002/ptr.1514

  • [6] Ramassamy C., Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: A review of their intracellular targets, Eur. J. Pharmacol., 2006, 545, 51–64 http://dx.doi.org/10.1016/j.ejphar.2006.06.025

  • [7] Leung K.W., Yung K.K., Mak N.K., Chan Y.S., Fan T.P., Wong R.N., Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity, Neuropharmacology, 2007, 52, 827–35 http://dx.doi.org/10.1016/j.neuropharm.2006.10.001

  • [8] Sierpinska A., Towards an integrated management of Dendrolimus pini L., Proceedings: Population dynamics, impacts, and integrated management of forest defoliation insects, USDA forest service general technical report NE, 1998, 247, 129–142

  • [9] Cunningham K.G., Hutchinson S.A., Manson W., Spring F.S., Cordycepin, a metabolic product from cultures of Cordyceps militaris (Linn.) Link, Nature, 1950, 166, 949 http://dx.doi.org/10.1038/166949a0

  • [10] Seldin D., Urbano S.L.A., McCaffrey F., Foss R., Phase I trial of cordycepin and deoxycoformycin in TdT-positive acute leukemia, Blood, 1997, 90, 246

  • [11] Zhou X.X., Meyer C.U., Schmidtke Zepp P.F., Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells, Eur. J. Pharmacol., 2002, 453, 309–317 http://dx.doi.org/10.1016/S0014-2999(02)02359-2

  • [12] Kim H.G., Shrestha B., Lim S.Y., Yoon D.H., Chang W.C., Shin D.J., et al., Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells, Eur. J. Pharmacol., 2006, 545, 192–199 http://dx.doi.org/10.1016/j.ejphar.2006.06.047

  • [13] Won S.Y., Park E.H., Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris, J. Ethnopharmacol., 2005, 96, 555–561 http://dx.doi.org/10.1016/j.jep.2004.10.009

  • [14] Yu R., Yang W., Song L., Yan C., Zhang Z., Zhao Y., Structural characterization and antioxidant activity of a polysaccharide from the fruiting bodies of cultured Cordyceps militaris, Carbohydr. Polym., 2007, 70, 430–436 http://dx.doi.org/10.1016/j.carbpol.2007.05.005

  • [15] Kim C.S., Lee S.Y., Cho S.H., Ko Y.M., Kim B.H., Kim H.J., et al., Cordyceps militaris induces the IL-18 expression via its promoter activation for IFN-gamma production, J. Ethnopharmacol., 2008, 120, 366–371 http://dx.doi.org/10.1016/j.jep.2008.09.010

  • [16] Hsu C.H., Sun H.L., Sheu J.N., Ku M.S., Hu C.M., Chan Y., et al., Effects of the immunomodulatory agent Cordyceps militaris on airway inflammation in a mouse asthma model, Pediatr. Neonatol., 2008, 49, 171–178 http://dx.doi.org/10.1016/S1875-9572(09)60004-8

  • [17] Nagatsu T., Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology, Essays Biochem., 1995, 30, 15–35

  • [18] Theofilopoulos S., Goggi J., Riaz S.S., Jauniaux E., Stern G.M., Bradford H.F., Parallel induction of the formation of dopamine and its metabolites with induction of tyrosine hydroxylase expression in foetal rat and human cerebral cortical cells by brain-derived neurotrophic factor and glial-cell derived neurotrophic factor, Brain Res. Dev. Brain Res., 2001, 127, 111–122 http://dx.doi.org/10.1016/S0165-3806(01)00125-0

  • [19] Lopez-Toledano M.A., Redondo C., Lobo M.V., Reimers D., Herranz A.S., Paino C.L., et al., Tyrosine hydroxylase induction by basic fibroblast growth factor and cyclic AMP analogs in striatal neural stem cells: role of ERK1/ERK2 mitogen-activated protein kinase and protein kinase C, J. Histochem. Cytochem., 2004, 52, 1177–1189 http://dx.doi.org/10.1369/jhc.3A6244.2004

  • [20] Gizang-Ginsberg E., Ziff E.B., Nerve growth factor regulates tyrosine hydroxylase gene transcription through a nucleoprotein complex that contains c-fos, Genes Dev., 1990, 4, 477–491 http://dx.doi.org/10.1101/gad.4.4.477

  • [21] Carroll J.M., Evinger M.J., Goodman H.M., Joh T.H., Differential and coordinate regulation of TH and PNMT mRNAs in chromaffin cell cultures by second messenger system activation and steroid treatment, J. Mol. Neurosci., 1991, 3, 75–83 http://dx.doi.org/10.1007/BF02885528

  • [22] Minner L.L., Pandalai S.P., Weisberg E.P., Sell S.L., Kovacs D.M., Kaplan B.B., Cold-induced alterations in the binding of adrenomedullary nuclear proteins to the promoter region of the tyrosine hydroxylase gene, J. Neurosci. Res., 1992, 33, 10–18 http://dx.doi.org/10.1002/jnr.490330103

  • [23] Nagamoto-Coombs K., Piech K.M., Best J.A., Sun B., Tank A.W., Tyrosine hydroxylase gene promoter activity is regulated by both cyclic AMP-responsive element and AP1 sites following calcium influx, Evidence for cyclic amp-responsive element binding protein-independent regulation, J. Biol. Chem., 1997, 272, 6051–6058 http://dx.doi.org/10.1074/jbc.272.9.6051

  • [24] Kim K.S., Lee M.K., Carroll J., Joh T.H., Both the basal and inducible transcription of the tyrosine hydroxylase gene are dependent upon a cAMP response element, J. Biol. Chem.,1993, 25, 15689–15695

  • [25] Tinti C., Conti B., Cubells F.J., Kim S.K., Baker H., Joh T.H., Inducible cAMP early repressor can modulate tyrosine hydroxylase gene expression after stimulation of cAMP synthesis, J. Biol. Chem., 1996, 271, 25375–25381 http://dx.doi.org/10.1074/jbc.271.41.25375

  • [26] Ng T.B., Wang H.X., Pharmacological actions of Cordyceps, a prized folk medicine, J. Pharm. Pharmacol., 2005, 57, 1509–1519 http://dx.doi.org/10.1211/jpp.57.12.0001

  • [27] Masocha W., Rottenberg M.E., Kristensson K., Migration of African trypanosomes across the blood-brain barrier, Physiol. Behav., 2007, 92, 110–114 http://dx.doi.org/10.1016/j.physbeh.2007.05.045

  • [28] Cho H.J., Cho J.Y., Rhee M.H., Park H.J., Cordycepin (3’-deoxyadenosine) inhibits human platelet aggregation in a cAMP- and cGMP-dependent manner, Eur. J. Pharmacol., 2007, 558, 43–51 http://dx.doi.org/10.1016/j.ejphar.2006.11.073

  • [29] Yu R.M., Song L.Y., Zhao Y., Bin W., Wang L., Zhang H., et al., Isolation and biological properties of polysaccharide CPS-1 from cultured Cordyceps militaris, Fitoterapia, 2004, 75, 465–472 http://dx.doi.org/10.1016/j.fitote.2004.04.003

  • [30] Kim C.S., Lee S.Y., Cho S.H., Ko Y.M., Kim B.H., Kim H.J., et al., Cordyceps militaris induces the IL-18 expression via its promoter activation for IFN-gamma production, J. Ethnopharmacol., 2008, 120, 366–371 http://dx.doi.org/10.1016/j.jep.2008.09.010

  • [31] Hwang I.K., Lim S.S., Yoo K.Y., Lee Y.S., Kim H.G., Kang I.L., et al., A phytochemically characterized extract of Cordyceps militaris and cordycepin protect hippocampal neurons from ischemic injury in gerbils, Planta Med., 2008, 74, 114–119 http://dx.doi.org/10.1055/s-2008-1034277

  • [32] Chicoine L.M., Bahr B.A., Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor-MAPK interactions, J. Neurosci Res., 2007, 85, 294–302 http://dx.doi.org/10.1002/jnr.21117

  • [33] Ho Y.S., Yu M.S., Yik S.Y., So K.F., Yuen W.H., Chang R.C., Polysaccharides from Wolfberry Antagonizes Glutamate Excitotoxicity in Rat Cortical neurons, Cell. Mol. Neurobiol., 2009, 29, 1233–1244 http://dx.doi.org/10.1007/s10571-009-9419-x

  • [34] Leveugle B., Ding W., Laurence F., Dehouck M.P., Scanameo A., Cecchelli R., et al., Heparin oligosaccharides that pass the blood-brain barrier inhibit beta-amyloid precursor protein secretion and heparin binding to beta-amyloid peptide, J. Neurochem., 1998, 70, 736–744 http://dx.doi.org/10.1046/j.1471-4159.1998.70020736.x

  • [35] Ma Q., Dudas B., Hejna M., Cornelli U., Lee J.M., Lorens S., et al., The blood-brain barrier accessibility of a heparin-derived oligosaccharides C3, Thromb. Res., 2002, 105, 447–453 http://dx.doi.org/10.1016/S0049-3848(02)00050-6

  • [36] Sakurai-Yamashita Y., Kinugawa H., Niwa M., Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal death of the hippocampus, Neurosci. Lett., 2006, 409, 30–34 http://dx.doi.org/10.1016/j.neulet.2006.09.041

  • [37] Sann H., Hoppe S., Baldwin L., Grundy D., Schemann M., Presence of putative neurotransmitters in the mesenteric plexus of the gastrointestinal tract and in the musculature of the urinary bladder of the ferret, Neurogastroenterol. Motil., 1998, 10, 35–47 http://dx.doi.org/10.1046/j.1365-2982.1998.00083.x

  • [38] Schemann M., Schaaf C., Mader M., Neurochemical coding of enteric neurons in the guinea pig stomach, J. Comp. Neurol., 1995, 353, 161–178 http://dx.doi.org/10.1002/cne.903530202

  • [39] Li Z.S., Pham T.D., Tamir H., Chen J.J., Gershon M.D., Enteric dopaminergic neurons: definition, developmental lineage, and effects of extrinsic denervation, J. Neurosci., 2004, 24, 1330–1339 http://dx.doi.org/10.1523/JNEUROSCI.3982-03.2004

  • [40] Tsukamoto K., Hayakawa T., Maeda S., Tanaka K., Seki M., Yamamura T., Projections to the alimentary canal from the dopaminergic neurons in the dorsal motor nucleus of the vagus of the rat, Auton. Neurosci., 2005, 123, 12–18

  • [41] Chevalier J., Derkinderen P., Gomes P., Thinard R., Naveilhan P., Vanden Berghe P., et al., Activity dependent regulation of tyrosine hydroxylase expression in the enteric nervous system, J. Physiol., 2008, 586, 1963–1975 http://dx.doi.org/10.1113/jphysiol.2007.149815

  • [42] Wood J.D., Enteric nervous system: Physiology, Encyclopedia of Neuroscience, Elsevier, 2009, 1103–1113

  • [43] Anlauf M., Schafer M.K., Eiden L., Weihe E., Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes, J. Comp. Neurol., 2003, 459, 90–111 http://dx.doi.org/10.1002/cne.10599

  • [44] Li Z.S., Schmauss C., Cuenca A., Ratcliffe E., Gershon M.D., Physiological modulation of intestinal motility by enteric dopaminergic neurons and the D2 receptor: analysis of dopamine receptor expression, location, development, and function in wild-type and knock-out mice, J. Neurosci., 2006, 26, 2798–2807 http://dx.doi.org/10.1523/JNEUROSCI.4720-05.2006

  • [45] Hayakawa T., Takanaga A., Tanaka K., Maeda S., Seki M., Distribution and ultrastructure of dopaminergic neurons in the dorsal motor nucleus of the vagus projecting to the stomach of the rat, Brain Res., 2004, 1006, 66–73 http://dx.doi.org/10.1016/j.brainres.2004.01.056

  • [46] Elenkov I.J., Wilder R.L., Chrousos G.P., Vizi E.S., The sympathetic nerve - an integrative interface between two supersystems: the brain and the immune system, Pharmacol. Rev., 2000, 52, 595–638

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