The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Synergistic Activation of Caspase-3 by m-Calpain after Neonatal Hypoxia-Ischemia
Open accessAbstract
The relative contributions of apoptosis and necrosis in brain injury have been a matter of much debate. Caspase-3 has been identified as a key protease in the execution of apoptosis, whereas calpains have mainly been implicated in excitotoxic neuronal injury. In a model of unilateral hypoxia-ischemia in 7-day-old rats, caspase-3-like activity increased 16-fold 24 h postinsult, coinciding with cleavage of the caspase-3 proenzyme and endogenous caspase-3 substrates. This activation was significantly decreased by pharmacological calpain inhibition, using CX295, a calpain inhibitor that did not inhibit purified caspase-3 in vitro. Activation of caspase-3 by m-calpain, but not mu-calpain, was facilitated in a dose-dependent manner in vitro by incubating cytosolic fractions, containing caspase-3 proform, with calpains. This facilitation required the presence of some active caspase-3 and could be abolished by including the specific calpain inhibitor calpastatin. This indicates that initial cleavage of caspase-3 by m-calpain, producing a 29-kDa fragment, facilitates the subsequent cleavage into active forms. This is the first report to our knowledge suggesting a direct link between the early, excitotoxic, calcium-mediated activation of calpain after cerebral hypoxia-ischemia and the subsequent activation of caspase-3, thus representing a tentative pathway of "pathological apoptosis."
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Cited by
Caspase Family Proteases and Apoptosis
Fan, T.-J., Han, L.-H., Cong, R.-S., & Liang, J. (2005) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2005.00108.x · Cited by 1,246
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Mitochondrial membrane permeabilization in neuronal injury
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Metadata
- Authors
- Blomgren, K., Zhu, C., Wang, X., Karlsson, J.-O., Leverin, A.-L., Bahr, B. A., Mallard, C., & Hagberg, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-03
- Volume
- 276
- Issue
- 13
- Pages
- 10191-10198
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2039992040
- Cited by
- 440
- References
- 52
- FWCI
- 11.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Blomgren, K., Zhu, C., Wang, X., Karlsson, J.-O., Leverin, A.-L., Bahr, B. A., Mallard, C., & Hagberg, H. (2001). Synergistic Activation of Caspase-3 by m-Calpain after Neonatal Hypoxia-Ischemia. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m007807200
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