| First Author | Nakamura Y | Year | 2014 |
| Journal | Cell Death Dis | Volume | 5 |
| Pages | e1215 | PubMed ID | 24810051 |
| Mgi Jnum | J:316051 | Mgi Id | MGI:6832362 |
| Doi | 10.1038/cddis.2014.181 | Citation | Nakamura Y, et al. (2014) Simultaneous loss of phospholipase Cdelta1 and phospholipase Cdelta3 causes cardiomyocyte apoptosis and cardiomyopathy. Cell Death Dis 5:e1215 |
| abstractText | Phospholipase C (PLC) is a key enzyme in phosphoinositide turnover. Among 13 PLC isozymes, PLCdelta1 and PLCdelta3 share high sequence homology and similar tissue distribution, and are expected to have functional redundancy in many tissues. We previously reported that the simultaneous loss of PLCdelta1 and PLCdelta3 caused embryonic lethality because of excessive apoptosis and impaired vascularization of the placenta. Prenatal death of PLCdelta1/PLCdelta3 double-knockout mice hampered our investigation of the roles of these genes in adult animals. Here, we generated PLCdelta1/PLCdelta3 double-knockout mice that expressed PLCdelta1 in extra-embryonic tissues (cDKO mice) to escape embryonic lethality. The cDKO mice were born at the expected Mendelian ratio, which indicated that the simultaneous loss of PLCdelta1 and PLCdelta3 in the embryo proper did not impair embryonic development. However, half of the cDKO mice died prematurely. In addition, the surviving cDKO mice spontaneously showed cardiac abnormalities, such as increased heart weight/tibial length ratios, impaired cardiac function, cardiac fibrosis, dilation, and hypertrophy. Predating these abnormalities, excessive apoptosis of their cardiomyocytes was observed. In addition, siRNA-mediated simultaneous silencing of PLCdelta1 and PLCdelta3 increased apoptosis in differentiated-H9c2 cardiomyoblasts. Activation of Akt and protein kinase C (PKC) theta was impaired in the hearts of the cDKO mice. siRNA-mediated simultaneous silencing of PLCdelta1 and PLCdelta3 also decreased activated Akt and PKCtheta in differentiated-H9c2 cardiomyoblasts. These results indicate that PLCdelta1 and PLCdelta3 are required for cardiomyocyte survival and normal cardiac function. |
