Poly(ADP-ribose) polymerase-1, ischemic preconditioning, and apoptosis in the rat myocardium / by Jeremy M. Byrd.
| Author/creator | Byrd, Jeremy M. 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 | 2001. |
| Description | 108 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | The purpose of this study was twofold: to determine whether inhibition of poly(ADP-ribose) polymerase-1 (PARP-1), a DNA repair enzyme, alters the levels of apoptosis in the ischemic myocardium and to ascertain whether the adaptive mechanisms of ischemic preconditioning are mediated through inhibition of PARP-1 activity. Male Sprague-Dawley rats were randomly divided into four different groups: a time control group (SHAM); a group subjected to a standard ischemic stress (ISC); a group subjected to ischemia preceded by ischemic preconditioning (IPC); and a group subjected to ischemia but pretreated with a drug to inhibit PARP-1 (DRUG). An ischemic insult was produced in the respective groups by occluding the left main coronary artery for 30 minutes, followed by 180 minutes of reperfusion. Those groups receiving IPC pretreatment underwent five cycles of non-necrosing ischemia/reperfusion, consisting of five minutes of ischemia, followed by five minutes of reperfusion (a total of 50 minutes). Oxidative injury was estimated by changes in nitrotyrosine (Western Blot), PARP activation/inactivation was estimated from the level of expression/cleavage of PARP-1 (Western Blot), the extent of necrosis was determined by histochemical techniques (TTC staining) and correlated with both functional recovery from ischemia (heart rate, mean arterial pressure, and rate pressure product measurements), and the degree of apoptosis (i.e., DNA fragmentation) incurred during ischemia (TUNEL assays). The results of this study suggest two things. First, IPC appears to confer protection to the myocardium primarily through mechanisms other than PARP-1 inhibition. Secondly, PARP-1 may play an active role in the apoptotic cascade in the myocardium. |
| General note | Presented 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 2001 |
| Bibliography note | Includes bibliographical references (leaves 92-107). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |