The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Direct Activation of Mitochondrial Apoptosis Machinery by c-Jun N-terminal Kinase in Adult Cardiac Myocytes
Open accessAbstract
Although oxidative stress causes activation of c-Jun N-terminal kinase (JNK) and apoptosis in many cell types, how the JNK pathway is connected to the apoptosis pathway is unclear. The molecular mechanism of JNK-mediated apoptosis was investigated in adult rat cardiac myocytes in culture as a model system that is sensitive to oxidative stress. Oxidative stress caused JNK activation, cytochrome c release, and apoptosis without new protein synthesis. Oxidative stress-induced apoptosis was abrogated by dominant negative stress-activated protein kinase/extracellular signal-regulated kinase kinase-1 (SEK1)-mediated inhibition of the JNK pathway, whereas activation of the JNK pathway by constitutively active SEK1 was sufficient to cause apoptosis. Inhibition of caspase-9, an apical caspase in the mitochondrial apoptosis pathway, suppressed oxidative stress-induced apoptosis, whereas inhibition of caspase-8 had no effect, indicating that both the JNK pathway and the mitochondrial apoptosis machinery are central to oxidative stress-induced apoptosis. Both JNK and SEK1 localized on mitochondria where JNK was activated by oxidative stress. Furthermore, active JNK caused the release of apoptogenic factors such as cytochrome c from isolated mitochondria in a cell-free assay. These findings indicate that the JNK pathway is a direct activator of mitochondrial death machinery without other cellular components and provide a molecular linkage from oxidative stress to the mitochondrial apoptosis machinery.
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Cites
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Cited by
Mitochondrial membrane permeabilization in cell death
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Mitogen-activated protein kinases in apoptosis regulation
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Cardiotoxicity of the cancer therapeutic agent imatinib mesylate
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Metadata
- Authors
- Aoki, H., Kang, P. M., Hampe, J., Yoshimura, K., Noma, T., Matsuzaki, M., & Izumo, S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 277
- Issue
- 12
- Pages
- 10244-10250
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2072232908
- Cited by
- 334
- References
- 31
- FWCI
- 10.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Aoki, H., Kang, P. M., Hampe, J., Yoshimura, K., Noma, T., Matsuzaki, M., & Izumo, S. (2002). Direct Activation of Mitochondrial Apoptosis Machinery by c-Jun N-terminal Kinase in Adult Cardiac Myocytes. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m112355200
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