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.
[1] Nagatsu T., Levitt M., Undenfriend S., Tyrosine hydroxylase, the initial step in norepinephrine biosynthesis, J. Biol. Chem., 1964, 239, 2910–2917 10.1016/S0021-9258(18)93832-9Search in Google Scholar
[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/s00702-009-0227-810.1007/s00702-009-0227-8Search in Google Scholar
[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.28.061604.13571810.1146/annurev.neuro.28.061604.135718Search in Google Scholar
[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.2004.05.00210.1016/j.pneurobio.2004.05.002Search in Google Scholar
[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.151410.1002/ptr.1514Search in Google Scholar
[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.2006.06.02510.1016/j.ejphar.2006.06.025Search in Google Scholar
[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.2006.10.00110.1016/j.neuropharm.2006.10.001Search in Google Scholar
[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 Search in Google Scholar
[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/10.1038/166949a010.1038/166949a0Search in Google Scholar
[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 Search in Google Scholar
[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)02359-210.1016/S0014-2999(02)02359-2Search in Google Scholar
[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.2006.06.04710.1016/j.ejphar.2006.06.047Search in Google Scholar PubMed
[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.2004.10.00910.1016/j.jep.2004.10.009Search in Google Scholar
[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.2007.05.00510.1016/j.carbpol.2007.05.005Search in Google Scholar
[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.2008.09.01010.1016/j.jep.2008.09.010Search in Google Scholar
[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)60004-810.1016/S1875-9572(09)60004-8Search in Google Scholar
[17] Nagatsu T., Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology, Essays Biochem., 1995, 30, 15–35 Search in Google Scholar
[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)00125-010.1016/S0165-3806(01)00125-0Search in Google Scholar
[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.3A6244.200410.1369/jhc.3A6244.2004Search in Google Scholar PubMed
[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.4.4.47710.1101/gad.4.4.477Search in Google Scholar PubMed
[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/BF0288552810.1007/BF02885528Search in Google Scholar PubMed
[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.49033010310.1002/jnr.490330103Search in Google Scholar PubMed
[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.272.9.605110.1074/jbc.272.9.6051Search in Google Scholar PubMed
[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 10.1016/S0021-9258(18)82311-0Search in Google Scholar
[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.271.41.2537510.1074/jbc.271.41.25375Search in Google Scholar PubMed
[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.57.12.000110.1211/jpp.57.12.0001Search in Google Scholar PubMed
[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.2007.05.04510.1016/j.physbeh.2007.05.045Search in Google Scholar PubMed
[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.2006.11.07310.1016/j.ejphar.2006.11.073Search in Google Scholar PubMed
[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.2004.04.00310.1016/j.fitote.2004.04.003Search in Google Scholar PubMed
[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.2008.09.01010.1016/j.jep.2008.09.010Search in Google Scholar PubMed
[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-2008-103427710.1055/s-2008-1034277Search in Google Scholar PubMed
[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.2111710.1002/jnr.21117Search in Google Scholar PubMed
[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-x10.1007/s10571-009-9419-xSearch in Google Scholar PubMed
[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.x10.1046/j.1471-4159.1998.70020736.xSearch in Google Scholar
[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)00050-610.1016/S0049-3848(02)00050-6Search in Google Scholar
[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.2006.09.04110.1016/j.neulet.2006.09.041Search in Google Scholar PubMed
[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.x10.1046/j.1365-2982.1998.00083.xSearch in Google Scholar PubMed
[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.90353020210.1002/cne.903530202Search in Google Scholar PubMed
[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.3982-03.200410.1523/JNEUROSCI.3982-03.2004Search in Google Scholar PubMed PubMed Central
[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 10.1016/j.autneu.2005.07.009Search in Google Scholar PubMed
[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.2007.14981510.1113/jphysiol.2007.149815Search in Google Scholar PubMed PubMed Central
[42] Wood J.D., Enteric nervous system: Physiology, Encyclopedia of Neuroscience, Elsevier, 2009, 1103–1113 10.1016/B978-008045046-9.00664-1Search in Google Scholar
[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.1059910.1002/cne.10599Search in Google Scholar PubMed
[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.4720-05.200610.1523/JNEUROSCI.4720-05.2006Search in Google Scholar PubMed PubMed Central
[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.2004.01.05610.1016/j.brainres.2004.01.056Search in Google Scholar PubMed
[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 Search in Google Scholar
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