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Titolo:
Akt activity in presenilin 1 wild-type and mutation transfected human SH-SY5Y neuroblastoma cells after serum deprivation and high glucose stress
Autore:
Vestling, M; Wiehager, B; Tanii, H; Cowburn, RF;
Indirizzi:
Karolinska Inst, Novum, KASPAC, Div Expt Geriatr,NEUROTEC,KFC, S-14157 Huddinge, Sweden Karolinska Inst Huddinge Sweden S-14157 EC,KFC, S-14157 Huddinge, Sweden Osaka Univ, Grad Sch Med, Dept Clin Neurosci, Osaka, Japan Osaka Univ Osaka Japan , Grad Sch Med, Dept Clin Neurosci, Osaka, Japan Karolinska Inst, Novum, Sumitomo Pharmaceut Alzheimer Ctr, KASPAC, S-14157Huddinge, Sweden Karolinska Inst Huddinge Sweden S-14157 KASPAC, S-14157Huddinge, Sweden
Titolo Testata:
JOURNAL OF NEUROSCIENCE RESEARCH
fascicolo: 3, volume: 66, anno: 2001,
pagine: 448 - 456
SICI:
0360-4012(20011101)66:3<448:AAIP1W>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLYCOGEN-SYNTHASE KINASE-3; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; PROTEIN-KINASE; CALCIUM HOMEOSTASIS; INCREASED EXPRESSION; HIPPOCAMPAL-NEURONS; MUTANT PRESENILIN-1; SIGNALING PATHWAY; INDUCED APOPTOSIS;
Keywords:
Alzheimer disease; Akt/protein kinase B; IGF-I; presenilin; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Cowburn, RF Karolinska Inst, Novum, KASPAC, Div Expt Geriatr,NEUROTEC,KFC,S-14157 Huddinge, Sweden Karolinska Inst Huddinge Sweden S-14157 157 Huddinge, Sweden
Citazione:
M. Vestling et al., "Akt activity in presenilin 1 wild-type and mutation transfected human SH-SY5Y neuroblastoma cells after serum deprivation and high glucose stress", J NEUROSC R, 66(3), 2001, pp. 448-456

Abstract

The majority of early-onset familial Alzheimer disease cases are caused bymutations in the genes encoding presenilin 1 (PS1) and presenilin 2 (PS2). Presenilin mutations have been hypothesised to cause Alzheimer disease either by altering amyloid precursor protein metabolism or by increasing the vulnerability of neurons to undergo death by apoptosis. We showed previouslythat PS1 exon 9 deletion (PS1 Delta E9) and L250S mutations predispose SH-SY5Y neuroblastoma cells to high glucose stress-induced apoptosis and that the anti-apoptotic effect of insulin-like growth factor I (IGF-I) is compromised by these mutations. The present study investigates whether the susceptibility of PS1 mutation transfected SH-SY5Y cells to undergo apoptosis is likely due to a downregulation of Akt/protein kinase B (Akt), a key intermediate in the phosphatidylinositol 3 (PI3)-kinase arm of the IGF-l signalingpathway. We used two methods to determine the regulation of Akt in response to the pro-apoptotic stimuli of serum deprivation and high glucose stress, as well as treatment with IGF-I. We also looked at the phosphorylatiom state of GSK-3 beta at Ser(9). Using a kinase assay with immunoprecipitated Akt, we detected an increased Akt activity in PS1 L250S cells at 1 hr after the combination of 20 mM glucose plus 10 nM IGF-I, when compared to the other cell types. This effect, however, was transient in that no mutation related differences were seen at either 6- or 24-hr post-treatment. Immunoblotting for Phospho-Akt as a ratio of total Akt, as well as for GSK-3 beta phosphorylated at Ser(9) revealed no apparent between cell type and treatment differences. This data strongly indicates that PS1 wt and mutant cells show no major differences in the pattern of Akt regulation after exposure to thepro-apoptotic stimuli of either serum deprivation or high glucose stress, or treatment with IGF-I. It is suggested that another component of IGF-I signaling is likely disrupted in these cells to increase their vulnerability to undergo death by apoptosis. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 16:21:11