Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation

Gerald W. Dorn; Miriam C. Souroujon; Tamar Liron; Che Hong Chen; Mary O. Gray; Hui Zhong Zhou; Michael Csukai; Guangyu Wu; John N. Lorenz; Daria Mochly-Rosen

doi:10.1073/pnas.96.22.12798

Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation

Gerald W. Dorn, Miriam C. Souroujon, Tamar Liron, Che Hong Chen, Mary O. Gray, Hui Zhong Zhou, Michael Csukai, Guangyu Wu, John N. Lorenz, Daria Mochly-Rosen

Life Sciences discipline

Research output: Contribution to journal › Article › peer-review

Abstract

Brief periods of cardiac ischemia trigger protection from subsequent prolonged ischemia (preconditioning). ε Protein kinase C (εPKC) has been suggested to mediate preconditioning. Here, we describe an εPKC-selective agonist octapeptide, ψε receptor for activated C-kinase (ψ®ACK), derived from an εPKC sequence homologous to its anchoring protein, εRACK. Introduction of ψεRACK into isolated cardiomyocytes, or its postnatal expression as a transgene in mouse hearts, increased εPKC translocation and caused cardio-protection from ischemia without any deleterious effects. Our data demonstrate that εPKC activation is required for protection from ischemic insult and suggest that small molecules that mimic this εPKC agonist octapeptide provide a powerful therapeutic approach to protect hearts at risk for ischemia.

Original language	English
Pages (from-to)	12798-12803
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	96
Issue number	22
DOIs	https://doi.org/10.1073/pnas.96.22.12798
State	Published - 26 Oct 1999

Keywords

Hypoxia
Ischemia
Preconditioning
Transgenic pseudoreceptors for activated C- kinase

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Dorn, G. W., Souroujon, M. C., Liron, T., Chen, C. H., Gray, M. O., Zhou, H. Z., Csukai, M., Wu, G., Lorenz, J. N., & Mochly-Rosen, D. (1999). Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation. Proceedings of the National Academy of Sciences of the United States of America, 96(22), 12798-12803. https://doi.org/10.1073/pnas.96.22.12798

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title = "Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation",

abstract = "Brief periods of cardiac ischemia trigger protection from subsequent prolonged ischemia (preconditioning). ε Protein kinase C (εPKC) has been suggested to mediate preconditioning. Here, we describe an εPKC-selective agonist octapeptide, ψε receptor for activated C-kinase (ψ{\textregistered}ACK), derived from an εPKC sequence homologous to its anchoring protein, εRACK. Introduction of ψεRACK into isolated cardiomyocytes, or its postnatal expression as a transgene in mouse hearts, increased εPKC translocation and caused cardio-protection from ischemia without any deleterious effects. Our data demonstrate that εPKC activation is required for protection from ischemic insult and suggest that small molecules that mimic this εPKC agonist octapeptide provide a powerful therapeutic approach to protect hearts at risk for ischemia.",

keywords = "Hypoxia, Ischemia, Preconditioning, Transgenic pseudoreceptors for activated C- kinase",

author = "Dorn, {Gerald W.} and Souroujon, {Miriam C.} and Tamar Liron and Chen, {Che Hong} and Gray, {Mary O.} and Zhou, {Hui Zhong} and Michael Csukai and Guangyu Wu and Lorenz, {John N.} and Daria Mochly-Rosen",

year = "1999",

month = oct,

day = "26",

doi = "10.1073/pnas.96.22.12798",

language = "אנגלית",

volume = "96",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Dorn, GW, Souroujon, MC, Liron, T, Chen, CH, Gray, MO, Zhou, HZ, Csukai, M, Wu, G, Lorenz, JN & Mochly-Rosen, D 1999, 'Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 22, pp. 12798-12803. https://doi.org/10.1073/pnas.96.22.12798

Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation. / Dorn, Gerald W.; Souroujon, Miriam C.; Liron, Tamar et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 22, 26.10.1999, p. 12798-12803.

Research output: Contribution to journal › Article › peer-review

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AU - Dorn, Gerald W.

AU - Souroujon, Miriam C.

AU - Liron, Tamar

AU - Chen, Che Hong

AU - Gray, Mary O.

AU - Zhou, Hui Zhong

AU - Csukai, Michael

AU - Wu, Guangyu

AU - Lorenz, John N.

AU - Mochly-Rosen, Daria

PY - 1999/10/26

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Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation

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