The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
An Inhibitor of p38 Mitogen-activated Protein Kinase Protects Neonatal Cardiac Myocytes from Ischemia
Open accessAbstract
Cellular ischemia results in activation of a number of kinases, including p38 mitogen-activated protein kinase (MAPK); however, it is not yet clear whether p38 MAPK activation plays a role in cellular damage or is part of a protective response against ischemia. We have developed a model to study ischemia in cultured neonatal rat cardiac myocytes. In this model, two distinct phases of p38 MAPK activation were observed during ischemia. The first phase began within 10 min and lasted less than 1 h, and the second began after 2 h and lasted throughout the ischemic period. Similar to previous studies using in vivo models, the nonspecific activator of p38 MAPK and c-Jun NH2-terminal kinase, anisomycin, protected cardiac myocytes from ischemic injury, decreasing the release of cytosolic lactate dehydrogenase by approximately 25%. We demonstrated, however, that a selective inhibitor of p38 MAPK, SB 203580, also protected cardiac myocytes against extended ischemia in a dose-dependent manner. The protective effect was seen even when the inhibitor was present during only the second, sustained phase of p38 MAPK activation. We found that ischemia induced apoptosis in neonatal rat cardiac myocytes and that SB 203580 reduced activation of caspase-3, a key event in apoptosis. These results suggest that p38 MAPK induces apoptosis during ischemia in cardiac myocytes and that selective inhibition of p38 MAPK could be developed as a potential therapy for ischemic heart disease.
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Cited by
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Metadata
- Authors
- Mackay, K., & Mochly-Rosen, D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 274
- Issue
- 10
- Pages
- 6272-6279
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2062567347
- Cited by
- 296
- References
- 41
- FWCI
- 22.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Mackay, K., & Mochly-Rosen, D. (1999). An Inhibitor of p38 Mitogen-activated Protein Kinase Protects Neonatal Cardiac Myocytes from Ischemia. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.10.6272
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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