Partial Inactivation of Cardiac 14-3-3 Protein in vivo Elicits Endoplasmic Reticulum Stress (ERS) and Activates ERS-initiated Apoptosis in ERS-induced Mice

作者：Sari Flori R; Watanabe Kenichi^*; Widyantoro Bambang; Thandavarayan Rajarajan A; Harima Meilei; Zhang Shaosong; Muslin Anthony J; Kodama Makoto; Aizawa Yoshifusa

来源：Cellular Physiology and Biochemistry, 2010, 26(2): 167-178.

DOI：10.1159/000320548

• 14-3-3
• Endoplasmic Reticulum stress
• Apoptosis
• Pressure overload

Background/Aims: Excessive endoplasmic reticulum stress (ERS) triggers apoptosis in various conditions including diabetic cardiomyopathy and pressure overload-induced cardiac hypertrophy and heart failure. The primary function of 14-3-3 protein is to inhibit apoptosis, but the roles of this protein in protecting against cardiac ERS and apoptosis are largely unknown. Methods: We investigated the roles of 14-3-3 protein in vivo during cardiac ERS and apoptosis induced by pressure overload or thapsigargin injection using transgenic (TG) mice that showed cardiac-specific expression of dominant negative (DN) 14-3-3 eta. Results: Cardiac positive apoptotic cells and the expression of glucose-regulated protein (GRP) 78, inositol-requiring enzyme (Ire) 1, tumor necrosis factor receptor (TNFR)-associated factor (TRAF) 2, CCAAT/enhancer binding protein homology protein (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased in the pressure-overload induced DN 14-3-3 eta mice compared with that in the WT mice. Furthermore, thapsigargin injection significantly increased the expression of GRP78 and TRAF2 expression in DN 14-3-3 eta mice compared with that in the WT mice. Conclusion: The enhancement of 14-3-3 protein may provide a novel protective therapy against cardiac ERS and ERS-initiated apoptosis, at least in part, through the regulation of CHOP and caspase-12 via the Ire1 alpha/TRAF2 pathway.

• 出版日期2010