Activation of caspase-3 in β-amyloid-induced apoptosis of cultured rat cortical neurons
Abstract
Amyloid beta protein (Abeta) has been thought to participate in the neurodegeneration associated with Alzheimer's disease. We here report on caspase-3 activation by Abeta-treatment of cultured neurons. Treatment of rat primary cortical culture with Abeta 25-35, an active fragment of Abeta, induced neuronal death as determined by a decrease in neuron-specific microtubule-associated protein 2 (MAP2)-like immunoreactivity and by the release of cellular lactate dehydrogenase (LDH). Abeta 25-35 also induced elevation of caspase-3-like Ac-DEVD-MCA cleavage activity in advance of neuronal death with similar concentration-dependency for neuronal death. Inhibitor sensitivity of the Abeta-induced proteolytic activity was similar to that of human recombinant caspase-3. Cleavage of pro-caspase-3 and cleavage of its endogenous substrates, poly (ADP-ribose) polymerase (PARP) and alpha-fodrin, were produced by Abeta-treatment. A caspase-3 inhibitor, Ac-DEVD-CHO, prevented Abeta-induced DNA fragmentation and cleavage of alpha-fodrin, but not of PARP. Caspase inhibitor of broad specificity, Z-VAD-CH(2)-DCB, additionally prevented Abeta-induced cleavage of PARP and some early loss of cell membrane integrity measured by LDH release. However, Abeta-induced condensation of nuclear chromatin and most of the late disintegration of cell membranes were not prevented in the presence of these caspase inhibitors. These results suggest that activation of both caspase-3 and caspase(s) other than caspase-3…
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Considerable evidence suggests that toxicity induced by both endogenous Aβ and extracellularly applied Aβ is mediated, at least in part, via the intrinsic, mitochondria-dependent apoptotic pathway.
“Considerable evidence suggests that toxicity induced by both endogenous Aβ and extracellularly applied Aβ is mediated, at least in part, via the intrinsic, mitochondria-dependent apoptotic pathway (Harada and Sugimoto, 1999; Cardoso et al., 2001; Casley et al., 2002b; Caspersen et al., 2005; Hansson Petersen et al., 2008; Cho et al., 2009; Takuma et al., 2009).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Harada and Sugimoto, 1999
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- Authors
- Harada, J., & Sugimoto, M.
- Corresponding author
- Harada, Jun
- ORCID
- Sugimoto, Masahiko
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 842
- Issue
- 2
- Pages
- 311-323
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2008354106
- Cited by
- 184
- References
- 1
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 9 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 7 · 2013: 8 · 2012: 4
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- caspase-3 activation, amyloid beta 25-35, apoptosis, cortical neurons, Alzheimer's disease, neurodegeneration, PARP cleavage, caspase inhibitors, Ac-DEVD-CHO, DNA fragmentation, MAP2, lactate dehydrogenase release
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Cerebral Cortex, Embryo, Mammalian, Enzyme Activation, Enzyme Inhibitors, Humans, Kinetics, Neurons, Peptide Fragments, Recombinant Proteins, Amyloid beta-Peptides, Rats, Sprague-Dawley, Apoptosis, Caspases, Rats, Caspase 3, Caspase Inhibitors
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