Inhibition of NF-kB renders cells more vulnerable to apoptosis induced by amyloid beta peptides.
One of the mechanisms leading to neurodegeneration during Alzheimer's disease (AD) is amyloid beta peptide neurotoxicity. In response to a variety of stress insults, namely oxidative stress, the transcription factor NF-kB can be activated. We have previously shown that amyloid beta peptides 25-35 and 1-40 (A beta 25-35 and A beta 1-40) induces cell death. In response to A beta 25-35 or 1-40 treatment, we observed an increase in superoxide dismutase (SOD) activity in NT2 cells. Amyloid beta peptides also induced an increase in SOD expression levels. This could result from NF-kB activation, as determined by the expression of p65. We observed that the NF-kB inhibitor, PDTC, prevented SOD overexpression after A beta treatment. Previously we have shown that A beta peptides could activate caspases-mediated apoptotic cell death. In this study, we analyzed if NF-kB activation prevented cells from caspases-activation and we also observed that inhibition of NF-kB by PDTC induced an increase in caspase-3 and caspase-6 activation. Taken together, these data suggest that pharmacological induction of NF-kB can be a potential target in Alzheimer's disease treatment.
Cardoso
S M
SM
Center for Neuroscience and Cellular Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal.
Oliveira
C R
CR
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013859:Thiocarbamates / Q000494:pharmacology; D014158:Transcription, Genetic
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D050863:Synaptotagmin I; D013859:Thiocarbamates; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D050857:Synaptotagmins; C066229:prolinedithiocarbamate; D011392:Proline; D013482:Superoxide Dismutase; D020169:Caspases