Protein kinase C delta and epsilon and time dependent change following ischemic preconditioning in a canine model of left ventricle hypertrophy / by Dirk J. Vice.
| Author/creator | Vice, Dirk J. author. |
| Other author | Lust, Robert M., degree supervisor. |
| Other author | Kalmus, Gerhard W., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 1999. |
| Description | viii, 97 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Ischemia/reperfusion (I/R) injury accounts for half the morbidity and mortality associated with cardiovascular disease. It has been found that found brief non-lethal episodes of ischemia with intervening reperfusion reduced infarction resulting from subsequent prolonged ischemic periods. Vigorous investigation of this phenomenon, now termed ischemic preconditioning (IPC), has indirectly implicated activation of protein kinase C (PKC) in mechanisms of both I/R injury and IPC. Investigation of this phenomenon in the context of chronically diseased myocardium is of paramount importance to the validity of IPC. Left ventricle hypertrophy (LVH) as a consequence of hypertension secondary to obesity and smoking accounts for a major portion of chronically diseased myocardium. To date LVH myocardium in any animal model, other than the rat, has failed to exhibit the infarct limiting effects of IPC seen in normal myocardium. PKC isozyme specifc functions in I/R and IPC in the LVH paradigm have not been elucidated. The purpose of the present study was to determine canine myocardial expression of PKC isoforms delta and epsilon in the LVH paradigm, and to characterize isoform specific responses to I/R injury and modulation by IPC. An open-chest canine model of regional ischemia was utilized. Twenty animals underwent one of two treatments following apical biopsy (baseline): 1) I/R= one hr. ischemia/three hr reperfusion, and 2) IPC= five min./ten min. (I/R) preconditioning followed by I/R protocol. Paired myocardial biopsies (anterior, posterior) were obtained at thirty min. ischemia (circumflex occlusion), one hr and three hr reperfusion for all groups. Additional biopsies were obtained during reperfusion of preconditioning period in IPC group. Soluble and particulate fractions were obtained following homogenization of biopsies, redistribution of PKC subtypes was determined by Western blot analysis. Results indicate canine myocardium in the LVH paradigm, express significantly less PKC delta and epsilon than measured in the normal left ventricle (NLV). Significant loss of PKC delta from the particulate fractions in I/R occurred following reperfusion and did not return to baseline levels. In contrast, particulate content of PKC e increased during ischemia in the non-ischemic region. Reperfusion elicited a response by PKC epsilon similar to PKC delta. The PKC epsilon response was region specific but PKC delta was not. IPC elicited no difference in either isoform distribution when compared to I/R. In conclusion, a PKC isozyme specific response to both I/R and IPC was not demonstrated in this LVH model. Any role that activation of these two isoforms might play in the mediation of myocardial protection by IPC is negated by the depressed levels found with LVH. |
| General note | Submitted to the faculty of the Department of Biology. |
| General note | Advisor: Robert M. Lust |
| General note | Advisor: Gerhard W. Kalmus |
| Dissertation note | M.S. East Carolina University 1999 |
| Bibliography note | Includes bibliographical references (leaves 88-97). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Joyner | University Archives | ASK AT SPECIAL COLLECTIONS DESK | ✔ Available | Request Material |
| Electronic Resources | ✔ Available |