Attenuation of CHOP-mediated Myocardial Apoptosis in Pressure-overloaded Dominant Negative p38α Mitogen-activated Protein Kinase Mice

Cellular Physiology and Biochemistry

关键词: Apoptosis;    Pressure overload;    p38 MAPK;    Endoplasmic reticulum stress;   

DOI  :  10.1159/000329970

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Pressure overload stimulation is known to elicit disturbances in the endoplasmic reticulum (ER), which leads to ER stress (ERS). p38 mitogen-activated protein kinase (MAPK) plays an important role in mediating apoptotic processes, however, the roles of this kinase in activating ERS-initiated apoptosis in pressure-overloaded hearts are largely unknown. Methods We clarified the role of p38α MAPK in ERS-associated apoptosis by subjecting transgenic mice displaying cardiac specific dominant negative (DN) mutant p38α MAPK over-expression to seven day pressure overload. Results Seven days pressure overload resulted in the same extent of cardiac hypertrophy and ERS in the wild-type (WT) and DN p38α mice compared with the sham mice. It also activated inositol-requiring enzyme (Ire)-1α and its downstream molecule, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2 in the WT and DN p38α mice compared with the sham mice. Interestingly, increased myocardial apoptosis and the up-regulation of CCAAT/enhancer binding protein homology protein (CHOP) expression compared with those in the sham mice were found in the aortic-banded WT mice, but not in the DN p38α mice. Conclusion Partial inhibition of p38α protein blocked the activation of CHOP-mediated apoptotic processes during pressure overload by partially inhibiting signaling from the Ire-1α/TRAF2 to its down-stream molecule, CHOP.

【 授权许可】

CC BY-NC-ND