title: Astaxanthin suppresses MPP(+)-induced oxidative damage in PC12 cells through a Sp1/NR1 signaling pathway.
abstract: OBJECTIVE
  To investigate astaxanthin (ATX) neuroprotection, and its mechanism, on a 1-methyl-4-phenyl-pyridine ion (MPP+)-induced cell model of Parkinson's disease.
  
  
  METHODS
  Mature, differentiated PC12 cells treated with MPP+ were used as an in vitro cell model. The MTT assay was used to investigate cell viability after ATX treatment, and western blot analysis was used to observe Sp1 (activated transcription factor 1) and NR1 (NMDA receptor subunit 1) protein expression, real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1.
  
  
  RESULTS
  PC12 cell viability was significantly reduced by MPP+ treatment. The expression of Sp1 and NR1 mRNA and protein were increased compared with the control (p < 0.01). Following co-treatment with ATX and MPP+, cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were decreased, compared with the MPP+ groups (p < 0.01). In addition, mithracycin A protected PC12 cells from oxidative stress caused by MPP+ by specifically inhibiting the expression of Sp1. Moreover, cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer.
  
  
  CONCLUSIONS
  ATX inhibited oxidative stress induced by MPP+ in PC12 cells, via the SP1/NR1 signaling pathway.
authors.affiliation: Department of Neurology, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, China. unionqyye@163.com
authors.forename: Qinyong
authors.initials: Q
authors.lastname: Ye
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Bixia
authors.initials: B
authors.lastname: Huang
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chen
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: C409466:NR1 NMDA receptor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016329:Sp1 Transcription Factor; D024341:Xanthophylls; C005948:astaxanthine; C066851:mithramycin A; D008926:Plicamycin; D015655:1-Methyl-4-phenylpyridinium
references.citation: Brain Res. 2010 Nov 11;1360:159-67
references.pmid: 20828541
references.citation: Forum Nutr. 2009;61:129-135
references.pmid: 19367117
references.citation: J Nutr Biochem. 2010 May;21(5):381-9
references.pmid: 19423317
references.citation: Nature. 2002 Feb 14;415(6873):793-8
references.pmid: 11823786
references.citation: J Neurosci Res. 2008 Apr;86(5):1142-52
references.pmid: 17969105
references.citation: Cancer Res. 2006 Nov 15;66(22):10805-14
references.pmid: 17108117
references.citation: Nutr Metab (Lond). 2010 Mar 05;7:18
references.pmid: 20205737
references.citation: Bioorg Med Chem. 2010 Apr 1;18(7):2631-8
references.pmid: 20227282
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7276-80
references.pmid: 1871133
references.citation: Free Radic Biol Med. 1992 Nov;13(5):581-3
references.pmid: 1334031
references.citation: FASEB J. 2009 Jun;23(6):1958-68
references.pmid: 19218497
references.citation: Int J Dev Neurosci. 2008 Feb;26(1):67-76
references.pmid: 17950559
references.citation: BMC Neurosci. 2012 Dec 29;13:156
references.pmid: 23272707
references.citation: Food Chem Toxicol. 2011 Jan;49(1):271-80
references.pmid: 21056612
references.citation: Brain Res. 2010 Nov 11;1360:40-8
references.pmid: 20846510
references.citation: Neurosci Res. 2004 Feb;48(2):195-202
references.pmid: 14741394
references.citation: Neurosci Lett. 2010 Oct 8;483(1):1-5
references.pmid: 20643188
references.citation: Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2719-25
references.pmid: 17660393
references.citation: Food Chem Toxicol. 2011 Aug;49(8):1773-81
references.pmid: 21554916
references.citation: J Food Sci. 2009 Sep;74(7):H225-31
references.pmid: 19895474
references.citation: Reprod Domest Anim. 2010 Dec;45(6):967-74
references.pmid: 19930137
references.citation: Free Radic Biol Med. 2010 Jul 15;49(2):192-204
references.pmid: 20385226
references.citation: Biochem Biophys Res Commun. 2010 Mar 19;393(4):773-8
references.pmid: 20171161
references.citation: Free Radic Biol Med. 2010 Jul 15;49(2):178-91
references.pmid: 20381604
references.citation: J Neurochem. 2008 Dec;107(6):1730-40
references.pmid: 19014378
references.citation: Neurochem Int. 2010 Mar;56(4):569-76
references.pmid: 20064569
references.citation: Cell Biol Int. 2008 Jan;32(1):22-30
references.pmid: 17936647
references.citation: J Neurosci. 2011 May 4;31(18):6858-70
references.pmid: 21543616
references.citation: Neurosignals. 2003 Nov-Dec;12(6):283-91
references.pmid: 14739558
references.citation: ScientificWorldJournal. 2010 Jul 20;10:1473-82
references.pmid: 20661539
references.citation: Neurosci Lett. 1984 Jul 13;48(1):87-92
references.pmid: 6332288
references.citation: Free Radic Biol Med. 2009 Oct 15;47(8):1212-20
references.pmid: 19660541
references.citation: J Clin Biochem Nutr. 2010 Sep;47(2):121-9
references.pmid: 20838567
references.citation: Neurobiol Aging. 2002 Sep-Oct;23(5):719-35
references.pmid: 12392777
references.citation: FASEB J. 2006 Nov;20(13):2375-7
references.pmid: 17012241
references.citation: J Toxicol Sci. 2010 Feb;35(1):41-7
references.pmid: 20118623
references.citation: J Neurochem. 2001 Aug;78(3):577-89
references.pmid: 11483661
references.citation: Ann Neurol. 1998 Sep;44(3 Suppl 1):S72-84
references.pmid: 9749577