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Involvement of calcineurin in the neurotoxic effects induced by amyloid‐beta and prion peptides
Author(s) -
Agostinho Paula,
Oliveira Catarina Resende
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02546.x
Subject(s) - calcineurin , neurotoxicity , programmed cell death , cytochrome c , intracellular , chemistry , microbiology and biotechnology , phosphatase , mitochondrion , amyloid beta , biochemistry , apoptosis , amyloid (mycology) , calmodulin , reactive oxygen species , peptide , biology , toxicity , enzyme , medicine , transplantation , inorganic chemistry , organic chemistry
It is usually accepted that prion and amyloid‐beta (Aβ) peptides induce apoptotic cell death. However, the mechanisms that trigger neuronal death, induced by these amyloidogenic peptides, remain to be clarified. In the present study we analysed the neurotoxic effects of the synthetic prion and Aβ peptides, PrP 106‐126 and Aβ 25−35 , in primary cultures of rat brain cortical cells. PrP 106‐126 and Aβ 25−35 incubated at a concentration of 25 µ m for 24 h, did not affect cell membrane integrity, but decreased the metabolic capacity of the cells. The intracellular free Ca 2+ concentration and reactive oxygen species levels increased significantly after 24 h treatment with PrP 106‐126 and Aβ 25−35 . Furthermore, these peptides (after 24 h exposure) also induced cytochrome c release from mitochondria and increased caspase‐3‐like activity. FK506, an inhibitor of the Ca 2+ /calmodulin‐dependent phosphatase, calcineurin, was able to prevent cytochrome c release, caspase‐3 activation and cell death induced by Aβ 25−35 or PrP 106‐126 peptides. Taken together these data suggest that calcineurin is involved in Aβ 25−35 and PrP 106‐126 neurotoxicity.