title: Caspase-8 Mediates Amyloid-β-induced Apoptosis in Differentiated PC12 Cells.
abstract: The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-β 1-40 (Aβ1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aβ-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aβ1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aβ1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aβ1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aβ1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.
authors: Department of Psychiatry, Third People's Hospital of Huzhou, Huzhou, 313000, Zhejiang, China.
authors: Min-cai
authors: MC
authors: Qian
authors: Jing
authors: J
authors: Liu
authors: Jia-shu
authors: JS
authors: Yao
authors: Wei-min
authors: WM
authors: Wang
authors: Jian-hong
authors: JH
authors: Yang
authors: Li-li
authors: LL
authors: Wei
authors: Yue-di
authors: YD
authors: Shen
authors: Wei
authors: W
authors: Chen
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
references: Nat Rev Neurosci. 2012 May 18;13(6):395-406
references: 22595785
references: Clin Sci (Lond). 2006 Feb;110(2):167-73
references: 16411893
references: J Cell Mol Med. 2011 Oct;15(10):2150-63
references: 21054783
references: J Neurosci. 1996 Dec 1;16(23):7533-9
references: 8922409
references: Brain Pathol. 2002 Oct;12(4):430-41
references: 12408229
references: J Immunol Methods. 1989 May 12;119(2):203-10
references: 2470825
references: Eur J Pharmacol. 2011 Jan 10;650(1):72-8
references: 20965163
references: Int J Biochem Cell Biol. 2009 Dec;41(12):2450-8
references: 19646546
references: Cell. 1994 Jun 17;77(6):817-27
references: 8004671
references: Chin Med J (Engl). 2013;126(10 ):1884-9
references: 23673104
references: Neurobiol Aging. 2015 Feb;36(2):886-900
references: 25541422
references: Biosci Biotechnol Biochem. 2005 Nov;69(11):2063-72
references: 16306686
references: Cell Tissue Res. 2013 Jul;353(1):139-51
references: 23660627
references: FASEB J. 2004 Nov;18(14):1755-7
references: 15364896
references: Antioxid Redox Signal. 2013 Sep 10;19(8):823-35
references: 23249141
references: Cell Res. 2007 Jun;17(6):565-71
references: 17339884
references: Mol Cell Biochem. 2012 Oct;369(1-2):55-65
references: 22752387
references: Neurosci Lett. 2004 Aug 26;367(1):113-7
references: 15308310
references: J Neurosci. 2009 Jan 28;29(4):1011-6
references: 19176810
references: Curr Opin Cell Biol. 2002 Dec;14(6):721-6
references: 12473345
references: J Neurosci. 2012 Oct 31;32(44):15565-76
references: 23115192
references: Neuroscience. 2003;119(2):399-419
references: 12770555
references: EMBO J. 1983;2(5):643-8
references: 6641712
references: Nat Rev Neurosci. 2005 Aug;6(8):603-14
references: 16062169
references: J Cell Biol. 2008 Feb 11;180(3):451-8
references: 18250198
references: J Biol Chem. 2009 Aug 14;284(33):21777-81
references: 19473994
references: J Neuropathol Exp Neurol. 2006 May;65(5):508-15
references: 16772874
references: Nat Cell Biol. 2002 Feb;4(2):95-105
references: 11788820
references: Blood. 2002 Jun 1;99(11):4070-8
references: 12010809
references: Microbiol Mol Biol Rev. 2000 Dec;64(4):821-46
references: 11104820
references: Open J Neurosci. 2013 Apr 8;3:null
references: 23795307
references: J Neurosci. 1992 Feb;12(2):376-89
references: 1346802
references: Biochem J. 1997 Aug 15;326 ( Pt 1):1-16
references: 9337844