title: Neurotrophic Activity of Cultured Cell Line U87 is Up-Regulated by Proline-Rich Polypeptide Complex and Its Constituent Nonapeptide.
abstract: Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor, as well as cytokines, for example, interleukin-6 (IL-6) play an important role in neuroprotection and in the control of the central nervous system (CNS) function. Reduced expression of neurotrophic factors can lead to dysregulation of neuron function and neuronal death. There is also evidence for mutual interactions between neurotrophins and IL-6. Therefore, the up-regulating the level of neuroprotective substances is one of the key manners to control the nervous system development and function. It can be a promising aim in the therapy of neurodegenerative disease in which the decreased level of neurotrophins is observed. In our recent studies, the role of proline-rich polypeptide complex (PRP) and its nonapeptide fragment (NP) in the regulation of neurotrophic activity in cultured astrocytes was shown. PRP and NP stimulate human astrocytoma cell line U87 to release the significant amounts of NGF to the extracellular space both in its precursor and mature form. We also provide the evidence that in NP-treated cells, the level of βNGF mRNA was increased. NP-treated cells used in this study produced also increasing amounts of IL-6. This finding indicates that PRP and its nonapeptide fragment NP up-regulate neurotrophic activity of U87 cell line by increase of NGF synthesis and its release into the extracellular space. It was also shown that NP-dependent increased production of IL-6 can enhance the NGF activity.
authors.affiliation: Department of Immunochemistry, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland. zablocka@iitd.pan.wroc.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zabłocka
authors.affiliation: Department of Microbiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Mitkiewicz
authors.affiliation: Department of Immunochemistry, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Józefa
authors.initials: J
authors.lastname: Macała
authors.affiliation: Department of Immunochemistry, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Janusz
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000494:pharmacology*; D055232:Proline-Rich Protein Domains / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C502240:NGF protein, human; D010446:Peptide Fragments; C579455:BDNF protein, human; D020932:Nerve Growth Factor
keywords: Brain-derived neurotrophic factor (BDNF); Human astrocytoma cell line U87; Interleukin-6; Nerve growth factor (NGF); Neuroprotection; Nonapeptide (NP); Proline-rich polypeptide complex (PRP)
references.citation: Biochem Biophys Res Commun. 2006 Jan 27;339(4):1021-8
references.pmid: 16337149
references.citation: Neuroscientist. 2013 Dec;19(6):604-15
references.pmid: 24122819
references.citation: Biol Pharm Bull. 1998 Dec;21(12):1267-70
references.pmid: 9881636
references.citation: Eur Cytokine Netw. 2001 Jul-Sep;12(3):462-7
references.pmid: 11566627
references.citation: CNS Neurol Disord Drug Targets. 2008 Feb;7(1):46-62
references.pmid: 18289031
references.citation: Neurochem Int. 2003 May;42(6):493-8
references.pmid: 12547648
references.citation: Neurosci Biobehav Rev. 2009 Mar;33(3):355-66
references.pmid: 18996146
references.citation: Glia. 2004 Aug 15;47(3):226-32
references.pmid: 15252811
references.citation: J Neurosci. 1999 Jul 1;19(13):5236-44
references.pmid: 10377335
references.citation: Acta Neurobiol Exp (Wars). 2010;70(4):454-67
references.pmid: 21196952
references.citation: Biofactors. 2014 Sep-Oct;40(5):501-12
references.pmid: 25042242
references.citation: Stem Cells Dev. 2006 Jun;15(3):407-21
references.pmid: 16846377
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64
references.pmid: 16939974
references.citation: Ann N Y Acad Sci. 2000;917:322-30
references.pmid: 11268359
references.citation: J Immunol Methods. 1986 May 22;89(2):271-7
references.pmid: 3486233
references.citation: J Neuropathol Exp Neurol. 2009 Aug;68(8):857-69
references.pmid: 19606067
references.citation: J Neurochem. 2004 Jun;89(5):1092-100
references.pmid: 15147501
references.citation: Biol Pharm Bull. 2008 Sep;31(9):1727-32
references.pmid: 18758067
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6735-40
references.pmid: 16618925
references.citation: Pharmacol Rep. 2014 Aug;66(4):618-23
references.pmid: 24948063
references.citation: J Neurosci Res. 2010 Oct;88(13):2798-809
references.pmid: 20568291
references.citation: FASEB J. 2004 Nov;18(14):1788-90
references.pmid: 15345694
references.citation: FEBS Lett. 2009 Jan 5;583(1):190-6
references.pmid: 19084010
references.citation: Neurosci Res. 2011 Apr;69(4):291-8
references.pmid: 21241747
references.citation: Curr Alzheimer Res. 2010 Jun;7(4):323-33
references.pmid: 19939229
references.citation: Int J Dev Neurosci. 2004 May;22(3):119-30
references.pmid: 15140465
references.citation: Mol Neurobiol. 1997 Dec;15(3):307-39
references.pmid: 9457704
references.citation: Neurotox Res. 2010 Apr;17(3):257-67
references.pmid: 19680737
references.citation: Science. 2001 Nov 30;294(5548):1945-8
references.pmid: 11729324
references.citation: Cell Mol Neurobiol. 2005 Nov;25(7):1123-39
references.pmid: 16392041
references.citation: Indian J Exp Biol. 2006 May;44(5):367-70
references.pmid: 16708888
references.citation: J Alzheimers Dis. 2004 Feb;6(1):17-26
references.pmid: 15004324
references.citation: Eur J Pharmacol. 2007 Dec 22;577(1-3):219-20
references.pmid: 17920057
references.citation: J Neurochem. 2004 May;89(3):581-92
references.pmid: 15086515
references.citation: J Neurosci. 2012 Feb 8;32(6):2002-12
references.pmid: 22323714
references.citation: Brain Res. 2006 Oct 20;1116(1):12-8
references.pmid: 16956589
references.citation: Acta Neuropathol. 2010 Jan;119(1):7-35
references.pmid: 20012068
references.citation: PLoS One. 2014;9(6):e99939
references.pmid: 24941200
references.citation: Int Immunopharmacol. 2007 Jul;7(7):981-8
references.pmid: 17499201
references.citation: J Neurosci Res. 1999 Jan 1;55(1):44-53
references.pmid: 9890433
references.citation: J Neurochem. 1996 Oct;67(4):1365-74
references.pmid: 8858917
references.citation: Trends Immunol. 2007 Mar;28(3):138-45
references.pmid: 17276138
references.citation: Glia. 1999 May;26(3):191-200
references.pmid: 10340760
references.citation: J Nutr Health Aging. 2009 Jun;13(6):522-7
references.pmid: 19536420
references.citation: Neuropeptides. 2005 Aug;39(4):419-26
references.pmid: 15890402
references.citation: Pharmacology. 2011;87(1-2):5-10
references.pmid: 21178384
references.citation: J Biomed Mater Res A. 2009 Nov;91(2):575-85
references.pmid: 18985780
references.citation: Prog Neurobiol. 2003 Apr;69(5):341-74
references.pmid: 12787574
references.citation: J Mol Neurosci. 2001 Dec;17(3):379-89
references.pmid: 11859934
references.citation: J Transl Med. 2012;10:239
references.pmid: 23190582
references.citation: Biochem Biophys Res Commun. 2013 Jan 11;430(2):512-8
references.pmid: 23232112
references.citation: Dev Neurobiol. 2010 Apr;70(5):372-83
references.pmid: 20186703
references.citation: Biochem Soc Trans. 2014 Oct;42(5):1286-90
references.pmid: 25233405
references.citation: J Biol Chem. 2009 Jul 3;284(27):18424-33
references.pmid: 19389705
references.citation: Front Cell Neurosci. 2014 Nov 06;8:378
references.pmid: 25414643
references.citation: Acta Biochim Biophys Sin (Shanghai). 2015 Apr;47(4):250-7
references.pmid: 25724352
references.citation: Evid Based Complement Alternat Med. 2013;2013:127075
references.pmid: 23878590
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14385-90
references.pmid: 14614143
references.citation: Biochem J. 1981 Oct 1;199(1):9-15
references.pmid: 7039618
references.citation: Acta Neurobiol Exp (Wars). 2006;66(4):343-58
references.pmid: 17265695
references.citation: Pharmacol Ther. 2013 May;138(2):155-75
references.pmid: 23348013
references.citation: Brain Pathol. 2006 Oct;16(4):320-32
references.pmid: 17107602
references.citation: Prog Brain Res. 2004;146:403-14
references.pmid: 14699976
references.citation: J Alzheimers Dis. 2010;21(2):597-610
references.pmid: 20571221
references.citation: J Neurosci Methods. 2007 Mar 15;160(2):264-8
references.pmid: 17049613