Bcl-x(L) inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloid(1-40) peptide in PC12 cells

Recent studies have shown that neuronal apoptosis induced by the Alzheimer' s disease (AD) beta-amyloid peptide (A beta) is related to alteration of th e 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-beta 1 is able to protect cultured neuronal cells from A beta-induced apoptosis via upregulation of bcl-X-L and bcl-2 gene e xpression. We show that A beta treatment (500 nM, freshly solubilized) resu lts in apoptosis and necrosis in differentiated PC12 cells maintained with a low dose of NGF-beta (1 ng/ml), To investigate whether transfection of PC 12 cells with bcl-X-L could block A beta-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 apoptosi s/necrosis produced by A beta treatment (1000 nM) in pcDNA3-bcl-X-L-transfe cted PC12 cells as compared with pcDNA3 vector-transfected PC12 cells. Thes e results suggest that Bcl-X-L exhibits both anti-necrotic as well as anti- apoptotic roles in A beta-challenged PC12 cells. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.