| First Author | Zhang M | Year | 2015 |
| Journal | Apoptosis | Volume | 20 |
| Issue | 9 | Pages | 1150-63 |
| PubMed ID | 26093524 | Mgi Jnum | J:337352 |
| Mgi Id | MGI:6757363 | Doi | 10.1007/s10495-015-1148-7 |
| Citation | Zhang M, et al. (2015) Notch3/Akt signaling contributes to OSM-induced protection against cardiac ischemia/reperfusion injury. Apoptosis 20(9):1150-63 |
| abstractText | Oncostatin M (OSM) exhibits many unique biological activities by activating the Obeta receptor. However, its role in myocardial ischemia/reperfusion injury (I/R injury) in mice remains unknown. We investigated whether Notch3/Akt signaling is involved in the regulation of OSM-induced protection against cardiac I/R injury. The effects of OSM were assessed in mice that underwent myocardial I/R injury by OSM treatment or by genetic deficiency of the OSM receptor Obeta. We investigated its effects on cardiomyocyte apoptosis and mitochondrial biogenesis and whether Notch3/Akt signaling was involved in the regulation of OSM-induced protection against cardiac I/R injury. The mice underwent 30 min of ischemia followed by 3 h of reperfusion and were randomized to be treated with Notch3 siRNA (siNotch3) or lentivirus carrying Notch3 cDNA (Notch3) 72 h before coronary artery ligation. Myocardial infarct size, cardiac function, cardiomyocyte apoptosis and mitochondria morphology in mice that underwent cardiac I/R injury were compared between groups. OSM alleviated cardiac I/R injury by inhibiting cardiomyocyte apoptosis through promotion of Notch3 production, thus activating the PI3K/Akt pathway. OSM enhanced mitochondrial biogenesis and mitochondrial function in mice subjected to cardiac I/R injury. In contrast, OSM receptor Obeta knock out exacerbated cardiac I/R injury, decreased Notch3 production, enhanced cardiomyocyte apoptosis, and impaired mitochondrial biogenesis in cardiac I/R injured mice. The mechanism of OSM on cardiac I/R injury is partly mediated by the Notch3/Akt pathway. These results suggest a novel role of Notch3/Akt signaling that contributes to OSM-induced protection against cardiac I/R injury. |
