Authors: Peng Luo Yongbo Zhao Dong Li Tao Chen Sanzhong Li Xiaodong Chao Wenbo Liu Lei Zhang Yan Qu Xiaofan Jiang Gang Lu Waisang Poon Zhou Fei
Publish Date: 2012/06/04
Volume: 17, Issue: 9, Pages: 975-988
Abstract
Although Homer 1 of the postsynaptic density regulates apoptosis the signaling mechanisms are not fully elucidated In this study we found that tumor necrosis factorα TNFα/cycloheximide CHX treatment transiently increased Homer 1a the short variant of Homer 1 but did not affect Homer 1b/c the long variant of Homer 1 Overexpression of Homer 1a blocked TNFα/CHXinduced apoptotic cell death whereas inhibition of Homer 1a induction enhanced the proapoptotic effect of TNFα/CHX treatment Moreover brainderived neurotrophic factor as a potential activator of endogenous Homer 1a inhibited apoptotic cell death after TNFα/CHX treatment through induction of Homer 1a Since three major mitogenactivated protein kinase MAPK pathways have important roles in apoptosis we examined if Homer 1a is involved in the effects of MAPK pathways on apoptosis It was shown that inhibition of the ERK1/2 pathway increased the expression and the protective effect of Homer 1a but inhibition of the p38 pathway produced the opposite effect Crosstalk among MAPK pathways was also associated with the regulation of Homer 1a during apoptotic cell death Blocking the p38 pathway increased the activity in the ERK1/2 pathway while inhibition of ERK1/2 pathway abolished the effect of p38 inhibitor on Homer 1a Furthermore Homer 1a reversely affected the activation of MAPK pathways These findings suggest that Homer 1a plays an important role in the prevention of apoptotic cell death and contributes to distinct regulatory effects of MAPK pathways on apoptotic cell deathWe would like to give our thanks to Ning Su Yihui Ma Kai Wang Junli Huo Juan Li Xiaoyan Chen and Yufen Shi for technical assistance The work was supported by National Natural Science Foundation of China Nos 30670796 30930093 and the 863 HighTech Project 2009AA02Z419
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