Bcl-X(L) inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloid1-40 peptide in PC12 cells.
Recent studies have shown that neuronal apoptosis induced by the Alzheimer's disease (AD) beta-amyloid peptide (Abeta) is related to alteration of the Bax/Bcl-2 ratio. It has been demonstrated that Bcl-X(L) (Bcl-X(L) = protein, bcl-X(L) = gene), a Bcl-2-related protein, prevents apoptosis in mammalian cells. Additionally, TGF-beta1 is able to protect cultured neuronal cells from Abeta-induced apoptosis via upregulation of bcl-X(L) and bcl-2 gene expression. We show that Abeta treatment (500 nM, freshly solubilized) results in apoptosis and necrosis in differentiated PC12 cells maintained with a low dose of NGF-beta (1 ng/ml). To investigate whether transfection of PC12 cells with bcl-X(L) could block Abeta-induced apoptosis, we transfected these cells with a bcl-X(L) construct (pcDNA-bcl-X(L)). Data show that bcl-X(L) significantly inhibits both early-stage apoptosis and late-stage apoptosis/necrosis produced by Abeta treatment (1000 nM) in pcDNA3-bcl-X(L)-transfected PC12 cells as compared with pcDNA3 vector-transfected PC12 cells. These results suggest that Bcl-X(L) exhibits both anti-necrotic as well as anti-apoptotic roles in Abeta-challenged PC12 cells.
Tan
J
J
The Roskamp Institute, Tampa, FL 33613-4799, USA. jtan@com1.med.usf.edu
Town
T
T
Placzek
A
A
Kundtz
A
A
Yu
H
H
Mullan
M
M
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D009336:Necrosis; D020932:Nerve Growth Factor / Q000235:genetics / Q000494:pharmacology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014162:Transfection / Q000235:genetics; D051020:bcl-X Protein
D016229:Amyloid beta-Peptides; C494813:Bcl2l1 protein, rat; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C078592:amyloid beta-protein (1-40); D051020:bcl-X Protein; D020932:Nerve Growth Factor