Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of β-amyloid on rat brain microvascular endothelial cells

  • Authors:
    • Marcella Folin
    • Silvia Baiguera
    • Lara Fioravanzo
    • Maria Teresa Conconi
    • Claudio Grandi
    • Gastone G. Nussdorfer
    • Pier Paolo Parnigotto
  • View Affiliations

  • Published online on: March 1, 2006     https://doi.org/10.3892/ijmm.17.3.431
  • Pages: 431-435
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Abstract

Several studies have demonstrated that cerebrovascular dysfunction and damage play a significant role in the pathogenesis of Alzheimer disease (AD). In fact, β-amyloid peptides (Aβs), the major component of the senile plaques and cerebrovascular amyloid deposits in AD, were shown to be cytotoxic to endothelial cells. We have recently observed that Aβs exert a toxic effect on neuromicrovascular endothelial cells (NECs) in a time- and concentration-dependent manner, apoptosis playing a pivotal role in this process. Hence, it seemed worthwhile to investigate the Aβ-mediated apoptosis mechanism in NECs. Aβs were found to induce, after a short incubation period, apoptosis throughout caspase-8 activation. Moreover, Aβs elicited a highly significant (p<0.001) increase in superoxide dismutase (SOD) levels after a 3-h exposure period, while SOD concentration was not affected after a 24-h incubation. The time-dependent increase in SOD concentration is probably correlated with the production of an excess of reactive oxygen species. Collectively, our findings allow us to conclude that: i) Aβs may induce apoptosis via the activation of caspase-8, presumably by cross-linking and activating receptors of the death-receptor family; ii) oxidative stress is possibly involved in the Aβ-induced cytotoxic effect; and iii) these two mechanisms do not act sequentially but, probably, are independent of each other.

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March 2006
Volume 17 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Folin M, Baiguera S, Fioravanzo L, Conconi MT, Grandi C, Nussdorfer GG and Parnigotto PP: Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of β-amyloid on rat brain microvascular endothelial cells. Int J Mol Med 17: 431-435, 2006.
APA
Folin, M., Baiguera, S., Fioravanzo, L., Conconi, M.T., Grandi, C., Nussdorfer, G.G., & Parnigotto, P.P. (2006). Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of β-amyloid on rat brain microvascular endothelial cells. International Journal of Molecular Medicine, 17, 431-435. https://doi.org/10.3892/ijmm.17.3.431
MLA
Folin, M., Baiguera, S., Fioravanzo, L., Conconi, M. T., Grandi, C., Nussdorfer, G. G., Parnigotto, P. P."Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of β-amyloid on rat brain microvascular endothelial cells". International Journal of Molecular Medicine 17.3 (2006): 431-435.
Chicago
Folin, M., Baiguera, S., Fioravanzo, L., Conconi, M. T., Grandi, C., Nussdorfer, G. G., Parnigotto, P. P."Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of β-amyloid on rat brain microvascular endothelial cells". International Journal of Molecular Medicine 17, no. 3 (2006): 431-435. https://doi.org/10.3892/ijmm.17.3.431