Amyloid β-peptide(1–40)-mediated oxidative stress in cultured hippocampal neurons
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Mechanism of amyloid β-peptide (Aβ) toxicity in cultured neurons involves the development of oxidative stress in the affected cells. A significant increase in protein carbonyl formation was detected in cultured hippocampal neurons soon after the addition of preaggregated Aβ(1–40), indicating oxidative damage of proteins. We report that neurons, subjected to Aβ(1–40), respond to Aβ oxidative impact by activation of antioxidant defense mechanisms and alternative ATP-regenerating pathway. The study demonstrates an increase of Mn SOD gene expression and the restoration of Cu, Zn SOD gene expression to a normal level after temporary suppression. Partial loss of creatine kinase (CK) BB activity, which is the key enzyme for functioning of the creatine/phosphocreatine shuttle, was compensated in neurons surviving the Aβ oxidative attack by increased production of the enzyme. As soon as the oxidative attack triggered by the addition of preaggregated Aβ(1–40) to rat hippocampal cell cultures has been extinguished, CK BB expression and SOD isoenzyme-specific mRNA levels in surviving neurons return to normal.
We propose that the maintenance of a constant level of CK function by increased CK BB production together with the induction of antioxidant enzyme gene expression in Aβ-treated hippocampal neurons accounts for at least part of their adaptation to Aβ toxicity.
Index EntriesAmyloid β-peptide oxidative stress protein carbonyls CK BB SOD
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- Aksenov M. Y., Aksenova M. V., Carney J. M., and Butterfield D. A. (1997a) Oxidative modification of glutamine synthetase by amyloid beta peptide.Free Radical Res. 27, 267–281.Google Scholar
- Behl C. and Sagara Y. (1997) Mechanism of amyloid beta protein induced neuronal cell death: current concepts and future perspectives.J. Neural Trans. Suppl. 49, 125–134.Google Scholar
- Butterfield D. A., Hensley K., Hall N., Subramaniam R., Howard B. J., Cole P., et al. (1996) Beta-amyloid-derived free radical oxidation: a fundamental process in Alzheimer’s disease, inMolecular Models of Dementia (Tanzi R. E. and Wasco W., eds.), Humana, Totowa, NJ, pp. 145–167.Google Scholar
- Chromczynski P. and Sacchi N. (1987) Single-step method of RNA isolation by acid guanidinum thiocyanate-phenol-chloroform extraction.Anal. Biochem. 162, 156–159.Google Scholar
- Iwasaki K., Sunderland T., Kusiak J. W., and Wolozin B. (1996) Changes in gene transcription during a beta-mediated cell death.Mol. Psych. 1, 65–71.Google Scholar
- Mark R. J., Blanc E. M., and Mattson M. P. (1996) Amyloid beta-peptide and oxidative cellular injury in Alzheimer’s disease.Mol. Neurobiol. 12, 211–224.Google Scholar
- Mattson M. P., Goodman Y., Luo H., Fu W., and Furukawa K. (1997) Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration.J. Neurosci. Res. 49, 681–697.PubMedCrossRefGoogle Scholar
- Sagara Y., Dargusch R., Klier F. G., Schubert D., and Behl C. (1996) Increased antioxidant enzyme activity in amyloid beta protein-resistant cells.J. Neurosci. 16, 497–505.Google Scholar
- Selkoe D. J. (1996) Amyloid β-protein and the genetics of Alzheimer’s disease.J. Biol. Chem. 271, 18,295–18,298.Google Scholar
- Takashima A., Yamaguchi H., Noguchi K., Michel G., Ishiguro K., Sato K., et al. (1995) Amyloid beta prptide induces cytoplasmic accumulation of amyloid protein precursor via tau protein kinase 1/glycogen synthase kinase-3 beta in rat hippocampal neurons.Neurosci. Lett. 198, 83–86.PubMedCrossRefGoogle Scholar