Bcl-2 overexpression protects against amyloid-beta and prion toxicity in GT1-7 neural cells.
In this study we analysed the effect of Bcl-2 on the cytotoxicity induced by the amyloid-beta (Abeta(25-35)) and prion (PrP(106-126)) peptides by using GT1-7puro and GT1-7bcl-2 (overexpressing the anti-apoptotic protein Bcl-2) neural cells. Exposure to Abeta(25-35) (1-5 microM) and PrP(106-126) (25 microM) caused a decrease in cell viability, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These data were correlated with Abeta(25-35) and PrP(106-126)-induced activation of caspase-9, which is linked to the mitochondrial death pathway, and the activation of the effector caspase-3, suggesting cell death by apoptosis. Furthermore, Bcl-2 overexpression protected from loss of cell viability and caspase-9 and -3 activation induced by Abeta(25-35) and PrP(106-126), showing that Bcl-2 is neuroprotective against apoptotic cell death caused by amyloidogenic peptides.
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Elisabete
E
Ferreiro
Ana
A
Eufrásio
Cláudia
C
Pereira
Catarina R
CR
Oliveira
A Cristina
AC
Rego
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D053148:Caspase 3; D053453:Caspase 9; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; C000599129:MYL4 protein, human; D018994:Myosin Light Chains; D011328:Prions; D011506:Proteins; D053148:Caspase 3; D053453:Caspase 9