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

GW Dorn, MC Souroujon, T Liron… - Proceedings of the …, 1999 - National Acad Sciences
GW Dorn, MC Souroujon, T Liron, CH Chen, MO Gray, HZ Zhou, M Csukai, G Wu, JN Lorenz…
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
Brief periods of cardiac ischemia trigger protection from subsequent prolonged ischemia
(preconditioning). ɛ Protein kinase C (ɛPKC) has been suggested to mediate
preconditioning. Here, we describe an ɛPKC-selective agonist octapeptide, ψɛ receptor for
activated C-kinase (ψɛRACK), derived from an ɛPKC sequence homologous to its
anchoring protein, ɛRACK. Introduction of ψɛRACK into isolated cardiomyocytes, or its
postnatal expression as a transgene in mouse hearts, increased ɛPKC translocation and …
Brief periods of cardiac ischemia trigger protection from subsequent prolonged ischemia (preconditioning). ɛ Protein kinase C (ɛPKC) has been suggested to mediate preconditioning. Here, we describe an ɛPKC-selective agonist octapeptide, ψɛ receptor for activated C-kinase (ψɛRACK), derived from an ɛPKC sequence homologous to its anchoring protein, ɛRACK. Introduction of ψɛRACK into isolated cardiomyocytes, or its postnatal expression as a transgene in mouse hearts, increased ɛPKC translocation and caused cardio-protection from ischemia without any deleterious effects. Our data demonstrate that ɛPKC activation is required for protection from ischemic insult and suggest that small molecules that mimic this ɛPKC agonist octapeptide provide a powerful therapeutic approach to protect hearts at risk for ischemia.
National Acad Sciences