| First Author | Gurusamy N | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 320 |
| Issue | 3 | Pages | 773-80 |
| PubMed ID | 15240115 | Mgi Jnum | J:91279 |
| Mgi Id | MGI:3046378 | Doi | 10.1016/j.bbrc.2004.06.023 |
| Citation | Gurusamy N, et al. (2004) Dominant negative 14-3-3 promotes cardiomyocyte apoptosis in early stage of type I diabetes mellitus through activation of JNK. Biochem Biophys Res Commun 320(3):773-80 |
| abstractText | 14-3-3 family members are dimeric, phosphoserine binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Recently, cardiomyocyte apoptosis has been characterized in type I diabetes mellitus. In order to study the molecular mechanism underlying diabetes-induced cardiomyocyte apoptosis, we examined the role of 14-3-3 protein and MAPK pathways in transgenic mice with cardiac specific expression of dominant negative 14-3-3eta (DN-14-3-3). p38 MAPK was highly activated 1, 28, and 56 days after diabetes induction by streptozotocin, whereas peak JNK activation was found on day 3 and decreased afterwards. In contrast, ERK1/2 were not activated in diabetic myocardium. Cardiomyocyte apoptosis was peaked on day 3 and decreased on 7, 28, and 56 days. p38 MAPK and JNK activation as well as cardiomyocyte apoptosis were greatly increased in DN-14-3-3 mice relative to non-transgenic mice. Moreover, we found a significant correlation between JNK activation and apoptosis in diabetic myocardium. These results indicate for the first time that 14-3-3 protein plays a critical anti-apoptotic role in diabetic myocardium by inhibiting the JNK pathway. |
