| First Author | Sreedhar R | Year | 2015 |
| Journal | Cell Signal | Volume | 27 |
| Issue | 4 | Pages | 770-6 |
| PubMed ID | 25599858 | Mgi Jnum | J:324541 |
| Mgi Id | MGI:6859121 | Doi | 10.1016/j.cellsig.2014.12.021 |
| Citation | Sreedhar R, et al. (2015) Myocardial 14-3-3eta protein protects against mitochondria mediated apoptosis. Cell Signal 27(4):770-6 |
| abstractText | There is a definite cardioprotective role for 14-3-3eta protein against pressure overload induced cardiac hypertrophy and streptozotocin induced cardiac dysfunction in type 1 diabetes mellitus (DM). But it is not conclusive whether it has any influence on mitochondrial mediated cardiomyocyte apoptosis in type 2 DM. In order to test this hypothesis, we have used C57BL6/J (WT) mice with cardiac specific dominant negative mutation of 14-3-3eta protein (DN 14-3-3eta). Both WT and DN 14-3-3eta mice were fed with high fat diet (HFD) for 12weeks. Their body weight and blood glucose levels were measured weekly and compared with standard diet (SD) fed mice. By the end of 12weeks, echocardiography was performed. Frozen myocardial sections were prepared to stain the apoptotic cardiomyocytes using TUNEL staining. DN 14-3-3eta mice fed with HFD showed cardiac dysfunction as identified by the decreased fractional shortening and ejection fraction and increased cardiomyocyte apoptosis in TUNEL staining. Western blotting analysis using mitochondrial fraction of the ventricular tissue homogenates showed a significant reduction in the level of cytochrome c suggesting its translocation into cytoplasm, which may be crucial in inducing cardiomyocyte apoptosis. In addition, DN 14-3-3eta mice depicted significantly increased levels of NADPH oxidase subunits suggesting oxidative stress, a significant reduction in phospho apoptosis signal-regulating kinase-1 (p-Ask-1) and increase in Ask-1 and phospho c-Jun N-terminal kinase (p-JNK) levels suggesting activation of Ask-1/JNK signaling. These results suggest that 14-3-3eta has a protective role against mitochondria mediated cardiomyocyte apoptosis with the involvement of Ask-1/JNK signaling during HFD induced type 2 DM. |
