IGF-1 reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt and MAPK/ERK1/2 signaling pathways.
Insulin-like growth factor 1 (IGF-1) stimulates α-secretase processing of amyloid precursor protein (APP) and decreases Aβ production. Little is known about the relationship between IGF-1 and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), the protease essential for the production of β-amyloid peptides (Aβ). Here, we investigated the effect of IGF-1 on BACE-1 in PC12 cells. Quantitative polymerase chain reaction analysis and western blot showed that treatment of cells with IGF-1 significantly decreased the levels of BACE-1 mRNA and protein. Furthermore, IGF-1 increased the phosphorylation of Akt and ERK1/2. The presence of the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 and the mitogen-activated protein kinase kinases (MEK) inhibitor PD98059 blocked the effect of IGF-1 on BACE-1. Our data indicated that IGF-1-induced reduction of BACE-1 might involve the PI3-K/Akt and MAPK/ERK1/2 signaling pathways.
Zhang
Hua
H
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
Gao
Ying
Y
Dai
Zhengwei
Z
Meng
Tao
T
Tu
Shengfen
S
Yan
Yong
Y
D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D016564:Amyloid beta-Protein Precursor; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
Prog Neurobiol. 2006 Jul;79(4):205-21
16916571
Protein Expr Purif. 2004 Apr;34(2):190-6
15003250
FEBS Lett. 2006 Sep 18;580(21):4984-90
16949582
Cell. 2005 Feb 25;120(4):545-55
15734686
J Am Geriatr Soc. 2005 Oct;53(10):1748-53
16181175
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11049-53
10500121
Ann Neurol. 2002 Jun;51(6):783-6
12112088
Hum Mol Genet. 2001 Jun 1;10(12):1317-24
11406613
J Biol Chem. 2007 Sep 7;282(36):26326-34
17616527
Nat Neurosci. 2005 Oct;8(10):1343-9
16136043
Nat Med. 2002 Dec;8(12):1390-7
12415260
Science. 1990 Jun 1;248(4959):1122-4
2111583
J Neurosci. 2005 Dec 14;25(50):11693-709
16354928
Cell Biol Int. 2008 Oct;32(10):1230-7
18675923
Nat Neurosci. 2001 Mar;4(3):231-2
11224535
Nature. 2003 May 22;423(6938):435-9
12761548
FASEB J. 2000 May;14(7):1015-22
10783157
Neuron. 2001 Oct 25;32(2):177-80
11683988
Nat Neurosci. 2001 Mar;4(3):233-4
11224536
Prog Neurobiol. 2003 Aug;70(6):443-62
14568359
Neurobiol Dis. 2007 Apr;26(1):134-45
17258906
Physiol Rev. 2001 Apr;81(2):741-66
11274343
Neurobiol Aging. 2006 Sep;27(9):1250-7
16183170
J Biol Chem. 1997 Aug 1;272(31):19547-53
9235959
J Neurochem. 2005 Feb;92(3):628-36
15659232
Eur J Pharmacol. 2004 Apr 19;490(1-3):127-33
15094079
J Neurosci. 2007 Apr 4;27(14):3639-49
17409228
Arch Neurol. 2002 Sep;59(9):1381-9
12223024
Nature. 1993 Jan 21;361(6409):260-3
7678698
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3632-7
14978286
Ageing Res Rev. 2005 May;4(2):195-212
16024298
Neuron. 2004 Jan 8;41(1):27-33
14715132
Neurobiol Aging. 2009 Oct;30(10):1563-73
18255190
J Biol Chem. 2007 Apr 6;282(14):10203-9
17301053
Peptides. 2006 Jul;27(7):1877-85
16574278