| First Author | Tzeng HP | Year | 2014 |
| Journal | J Am Heart Assoc | Volume | 3 |
| Issue | 1 | Pages | e000662 |
| PubMed ID | 24572254 | Mgi Jnum | J:329605 |
| Mgi Id | MGI:6843473 | Doi | 10.1161/JAHA.113.000662 |
| Citation | Tzeng HP, et al. (2014) Dysferlin mediates the cytoprotective effects of TRAF2 following myocardial ischemia reperfusion injury. J Am Heart Assoc 3(1):e000662 |
| abstractText | BACKGROUND: We have demonstrated that tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), a scaffolding protein common to TNF receptors 1 and 2, confers cytoprotection in the heart. However, the mechanisms for the cytoprotective effects of TRAF2 are not known. METHODS/RESULTS: Mice with cardiac-restricted overexpression of low levels of TRAF2 (MHC-TRAF2LC) and a dominant negative TRAF2 (MHC-TRAF2DN) were subjected to ischemia (30-minute) reperfusion (60-minute) injury (I/R), using a Langendorff apparatus. MHC-TRAF2LC mice were protected against I/R injury as shown by a significant approximately 27% greater left ventricular (LV) developed pressure after I/R, whereas mice with impaired TRAF2 signaling had a significantly approximately 38% lower LV developed pressure, a approximately 41% greater creatine kinase (CK) release, and approximately 52% greater Evans blue dye uptake after I/R, compared to LM. Transcriptional profiling of MHC-TRAF2LC and MHC-TRAF2DN mice identified a calcium-triggered exocytotic membrane repair protein, dysferlin, as a potential cytoprotective gene responsible for the cytoprotective effects of TRAF2. Mice lacking dysferlin had a significant approximately 39% lower LV developed pressure, a approximately 20% greater CK release, and approximately 29% greater Evans blue dye uptake after I/R, compared to wild-type mice, thus phenocopying the response to tissue injury in the MHC-TRAF2DN mice. Moreover, breeding MHC-TRAF2LC onto a dysferlin-null background significantly attenuated the cytoprotective effects of TRAF2 after I/R injury. CONCLUSION: The study shows that dysferlin, a calcium-triggered exocytotic membrane repair protein, is required for the cytoprotective effects of TRAF2-mediated signaling after I/R injury. |
