Title

Protein Kinase Beta II (PKC-βІI) inhibitor exerts cardioprotective effects in Myocardial Ischemia/Reperfusion Injury (MI/R)

Date of Award

2019

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Lindon Young, PhD

Second Advisor

Qian Chen, PhD

Third Advisor

Cathy Hatcher, PhD

Abstract

During myocardial ischemia/reperfusion (I/R), the generation of reactive oxygen species (ROS) contributes to the post-reperfused cardiac injury and contractile dysfunction. Activation of Protein Kinase C beta II (PKC βII) has been associated with increased ROS release from myocardial I/R tissue, decreased endothelial-derived nitric oxide, and increased infarct size. We tested the hypothesis that using a cell permeable PKC βII peptide inhibitor (PKC βII-) (N-myr-SLNPEWNET, MW=1300 g/mol, 10μM or 20μM) will attenuate infarct size and improve post-reperfused cardiac function compared to untreated controls in isolated perfused rat hearts subjected to I(30min)/R(90 min). PKC βII- treated hearts (both 10 and 20 μM) significantly improved postreperfused cardiac function (e.g. left ventricular developed pressure [LVDP], and dP/dt max) compared to controls (all p

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