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Proteasome inhibition ablates activation of NF-kappa B in myocardial reperfusion and reduces reperfusion injury.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Pye, Joseph Ardeshirpour, Farhad McCain, Arlene S. Bellinger, Dwight A. Merricks, Elizabeth P. Adams, Julian Elliott, Peter J. Pien, Christine Fischer, Thomas Baldwin, Albert S. Nichols, Timothy C. |
| Copyright Year | 2003 |
| Abstract | Both acute coronary occlusion and reperfusion of an infarct-related artery lead to significant myocardial cell death. Recent evidence has been presented that activation of the transcription factor nuclear factor-kappaB (NF-kappaB) plays a critical role in reperfusion injury. NF-kappaB is usually bound to its inhibitor, IkappaB, and classic activation of NF-kappaB occurs when the 20S proteasome degrades IkappaB that has been phosphorylated and ubiquitinated. In this study, activation of NF-kappaB was inhibited by systemic administration of a 20S proteasome inhibitor (PS-519) in a porcine model of myocardial reperfusion injury. The experimental protocol induced myocardial ischemia in the distribution of the left anterior descending coronary artery for 1 h with subsequent reperfusion for 3 h. A single systemic treatment with PS-519 reduced 20S proteasome activity; blocked activation of NF-kappaB induced by reperfusion; reduced creatine kinase, creatine kinase-muscle-brain fraction, and troponin I release from the myocardium; preserved regional myocardial function measured by segmental shortening; significantly reduced the size of myocardial infarction; and exhibited no acute toxicity. These data show that myocardial reperfusion injury can be inhibited by using proteasome inhibitors, which likely function through the inhibition of NF-kappaB activation. |
| Starting Page | 239 |
| Ending Page | 243 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/ajpheart/284/3/H919.full.pdf |
| PubMed reference number | 12424098v1 |
| Volume Number | 284 |
| Issue Number | 3 |
| Journal | American journal of physiology. Heart and circulatory physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adverse reaction to drug Anterior descending branch of left coronary artery Biologic Preservation Cardiomyopathies Cell Death Cellular Phone Coronary Occlusion Creatine Kinase I-kappa B Proteins Muscle Myocardial Infarction Myocardial Ischemia Myocardial Reperfusion Injury Myocardium Myocytes, Cardiac NF-kappa B PS519 Porcine species Proteasome inhibitor Reperfusion Therapy Troponin I Ubiquitin |
| Content Type | Text |
| Resource Type | Article |
