Comparing the Efficacy of Pharmacological Preconditioning with Myristic Acid-conjugated, TAT- conjugated and Native Protein Kinase C Epsilon Peptide Activator in Myocardial Ischemia/Reperfusion (MI/R) Models
Date of Award
Master of Science in Biomedical Sciences
Lindon Young, PhD
Robert Barsotti, PhD
Cathy Hatcher, PhD
Protein kinase C epsilon (PKCε) activation is a central mediator of the cardioprotection conferred by myocardial ischemic preconditioning (IPC). PKCε activation via PKCε peptide activator (PKCε+, HDAPIGYD) prior to ischemia is a pharmacologic mimic of IPC. However, native PKCε+ requires the use of cell permeabilization methods, such as conjugation to known carrier peptides, for effective intracellular targeting to mitigate cardiac damage. Our study compares PKCε+ conjugated to either myristic acid (Myr- PKCε+) or transactivating (TAT) carrier peptide (YGRKKRRQRRR-CC- PKCε+) with native PKCε+ pretreatment and untreated control I/R hearts to evaluate the efficacy of these cell permeable peptide analogs in attenuating contractile dysfunction and infarct size after MI (30min)/R (90min). Infarct size was assessed by 1% triphenyltetrazolium chloride staining of heart tissue, which was evaluated using NIH ImageJ software pixel analysis and weight dissection analysis. ImageJ pixel analysis showed significantly reduced infarct size in the Myr-PKCε+ (29±1%, p
McIntyre, Anahi, "Comparing the Efficacy of Pharmacological Preconditioning with Myristic Acid-conjugated, TAT- conjugated and Native Protein Kinase C Epsilon Peptide Activator in Myocardial Ischemia/Reperfusion (MI/R) Models" (2019). PCOM Biomedical Studies Student Scholarship. 185.