title: Neuroprotective activities of catalpol against CaMKII-dependent apoptosis induced by LPS in PC12 cells.
abstract: OBJECTIVE
  Neurodegenerative diseases present progressive neurological disorder induced by cell death or apoptosis. Catalpol, an iridoid glucoside isolated from the root of Rehmannia glutinosa Libosch, is present in a wide range of plant families. Although catalpol is an effective anti-apoptotic agent in LPS-induced neurodegeneration, the underlying mechanism has not been established. Here we have identified some of the mechanisms involved the prevention by catalpol of apoptosis induced by LPS in an experimental model of neurodegeneration in vitro.
  
  
  METHODS
  Apoptosis was induced by adding LPS (80 ng·mL(-1)) to pheochromocytoma (PC12) cells, pretreated with catalpol for 12 h. We measured intracellular reactive oxygen species (ROS), apoptosis and intracellular calcium concentration ([Ca(2+)]i) by flow cytometry or laser confocal scanning microscopy. We also analysed the protein expression of Bcl-2, Bax and Ca(2+)-calmodulin-dependent protein kinase II (CaMKII)-dependent apoptosis signal-regulating kinase-1 (ASK-1)/JNK/p38 signalling pathway in PC12 cells by Western blot.
  
  
  RESULTS
  Catalpol stimulated expression of Bcl-2 and inhibited the expression of Bax. Catalpol also attenuated the increase in Ca(2+) concentration induced by LPS in PC12 cells and down-regulated CaMK phosphorylation. The CaMKII-dependent ASK-1/JNK/p38 signalling cascade was blocked by catalpol. All these changes were accompanied by a decrease of apoptosis induced by LPS in PC12 cells.
  
  
  CONCLUSIONS
  The data presented here provide new mechanistic insights into the links between the CaMKII-dependent ASK-1/JNK/p38 signalling pathway and the protective effect of catalpol on apoptosis induced by LPS in PC12 cells.
authors.affiliation: Center of Teaching & Research, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Chen
authors.forename: Ximing
authors.initials: X
authors.lastname: Li
authors.forename: Lian-Qun
authors.initials: LQ
authors.lastname: Jia
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Diandong
authors.initials: D
authors.lastname: Hou
authors.forename: Junyan
authors.initials: J
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D011494:Protein Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D057888:Iridoid Glucosides; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C078040:catalpol; D011494:Protein Kinases
references.citation: Biochim Biophys Acta. 2007 Oct;1773(10):1491-9
references.pmid: 17888529
references.citation: J Mol Cell Cardiol. 2010 Jun;48(6):1298-306
references.pmid: 20060004
references.citation: Nat Rev Neurol. 2011 Dec 06;8(1):11-2
references.pmid: 22143361
references.citation: Nature. 2006 Oct 19;443(7113):780-6
references.pmid: 17051204
references.citation: J Invest Dermatol. 2001 Aug;117(2):333-40
references.pmid: 11511312
references.citation: EMBO Rep. 2001 Mar;2(3):222-8
references.pmid: 11266364
references.citation: Biochim Biophys Acta. 2009 Jun;1793(6):959-70
references.pmid: 19133301
references.citation: Neuron. 2008 Sep 25;59(6):914-31
references.pmid: 18817731
references.citation: Mol Cell. 2009 Nov 13;36(3):487-99
references.pmid: 19917256
references.citation: Ann N Y Acad Sci. 2002 Oct;971:86-8
references.pmid: 12438095
references.citation: Histochem Cell Biol. 2012 Sep;138(3):489-501
references.pmid: 22614950
references.citation: Cancer Immunol Immunother. 2012 Oct;61(10):1755-68
references.pmid: 22419372
references.citation: Apoptosis. 2010 Dec;15(12):1480-93
references.pmid: 20640600
references.citation: Nat Med. 2009 Mar;15(3):331-7
references.pmid: 19198615
references.citation: J Neural Transm (Vienna). 2010 Aug;117(8):971-9
references.pmid: 20571837
references.citation: J Clin Invest. 2009 Oct;119(10):2925-41
references.pmid: 19741297
references.citation: Antioxid Redox Signal. 2009 Sep;11(9):2333-9
references.pmid: 19243235
references.citation: Biol Pharm Bull. 1996 Jun;19(6):791-5
references.pmid: 8799474
references.citation: Oncogene. 2004 Apr 12;23(16):2838-49
references.pmid: 15077147
references.citation: Brain Res. 2008 Jan 10;1188:139-47
references.pmid: 18022141
references.citation: Toxicol Appl Pharmacol. 2000 Apr 15;164(2):149-60
references.pmid: 10764628
references.citation: Nature. 2006 Oct 19;443(7113):796-802
references.pmid: 17051206
references.citation: Int J Dev Neurosci. 2007 Dec;25(8):509-14
references.pmid: 17981425
references.citation: Int J Biol Sci. 2010 Aug 20;6(5):443-53
references.pmid: 20827397
references.citation: Int J Cancer. 2011 Apr 1;128(7):1724-35
references.pmid: 20503275
references.citation: Mol Cell. 2009 Feb 13;33(3):377-88
references.pmid: 19217411
references.citation: Expert Opin Ther Targets. 2009 Jun;13(6):653-64
references.pmid: 19456270
references.citation: Eur J Cell Biol. 2009 Dec;88(12):753-63
references.pmid: 19717209
references.citation: Dev Cell. 2011 Jul 19;21(1):92-101
references.pmid: 21763611
references.citation: Cell. 2005 Oct 7;123(1):89-103
references.pmid: 16213215
references.citation: Toxicon. 2004 Jan;43(1):53-9
references.pmid: 15037029
references.citation: Mutat Res. 2009 Mar 31;674(1-2):137-47
references.pmid: 18955158
references.citation: Prostate. 2008 Nov 1;68(15):1624-34
references.pmid: 18668529
references.citation: Life Sci. 2006 Dec 23;80(3):193-9
references.pmid: 17049947
references.citation: Nature. 1982 May 13;297(5862):152-4
references.pmid: 7078629
references.citation: Cell Biol Int. 2012 May 1;36(5):419-26
references.pmid: 22126839
references.citation: Br J Pharmacol. 2002 Jul;136(6):938-46
references.pmid: 12110618
references.citation: Neurobiol Dis. 2011 Jan;41(1):177-88
references.pmid: 20850531
references.citation: Int Immunopharmacol. 2011 Feb;11(2):212-9
references.pmid: 21115120