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Caspase 8 mediated apoptotic cell death induced by β‐sheet forming polyalanine peptides
Author(s) -
Giri Kalyan,
Ghosh Utpal,
Bhattacharyya Nitai P,
Basak Soumen
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01294-8
Subject(s) - apoptosis , caspase , cytochrome c , programmed cell death , peptide , toxicity , oculopharyngeal muscular dystrophy , chemistry , alanine , caspase 3 , beta sheet , microbiology and biotechnology , biochemistry , biology , amino acid , muscular dystrophy , genetics , organic chemistry
Expansion of a polyalanine stretch from 10 to 12–17 residues in the N‐terminus of the protein PABP2 has been implicated in the genetically acquired disease oculopharyngeal muscular dystrophy, characterized by nuclear protein deposits. Here we report a correlation between the structural properties and cell toxicity of two peptides mimicking the N‐terminal domain of PABP2: one containing seven and the other 11 uninterrupted alanine residues. Consistent with earlier observations, the longer peptide (11‐ala) was found to adopt β‐sheet structure while the shorter one (7‐ala) formed α‐helix over a wide range of concentrations (∼20–500 μM). We observed that treatment with 11‐ala resulted in significantly enhanced death of Chinese hamster V79 cells, compared to the effect of treatment with 7‐ala, via the cytochrome c mediated apoptotic pathway. Increases in caspase 8 and caspase 3 activity were also observed in human cells (K562) treated with 11‐ala. These results indicate that the toxicity of pathogenic peptides is directly linked to their β‐sheet structure and also support recent observations that small oligomeric species of peptides and proteins are the key toxic elements in causing protein aggregation diseases.