The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and ɛPKC
Open accessAbstract
Conflicting roles for protein kinase C (PKC) isozymes in cardiac disease have been reported. Here, δPKC-selective activator and inhibitor peptides were designed rationally, based on molecular modeling and structural homology analyses. Together with previously identified activator and inhibitor peptides of ɛPKC, δPKC peptides were used to identify cardiac functions of these isozymes. In isolated cardiomyocytes, perfused hearts, and transgenic mice, δPKC and ɛPKC had opposing actions on protection from ischemia-induced damage. Specifically, activation of ɛPKC caused cardioprotection whereas activation of δPKC increased damage induced by ischemia in vitro and in vivo . In contrast, δPKC and ɛPKC caused identical nonpathological cardiac hypertrophy; activation of either isozyme caused nonpathological hypertrophy of the heart. These results demonstrate that two related PKC isozymes have both parallel and opposing effects in the heart, indicating the danger in the use of therapeutics with nonselective isozyme inhibitors and activators. Moreover, reduction in cardiac damage caused by ischemia by perfusion of selective regulator peptides of PKC through the coronary arteries constitutes a major step toward developing a therapeutic agent for acute cardiac ischemia.
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Metadata
- Authors
- Chen, L., Hahn, H., Wu, G., Chen, C.-H., Liron, T., Schechtman, D., Cavallaro, G., Banci, L., Guo, Y., Bolli, R., Dorn, G. W., & Mochly-Rosen, D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-09-11
- Volume
- 98
- Issue
- 20
- Pages
- 11114-11119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2082473607
- Cited by
- 538
- References
- 32
- FWCI
- 22.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, L., Hahn, H., Wu, G., Chen, C.-H., Liron, T., Schechtman, D., Cavallaro, G., Banci, L., Guo, Y., Bolli, R., Dorn, G. W., & Mochly-Rosen, D. (2001). Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and ɛPKC. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.191369098
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