NDLI: Protective effect of Homer 1a on tumor necrosis factor-α with cycloheximide-induced apoptosis is mediated by mitogen-activated protein kinase pathways

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Protective effect of Homer 1a on tumor necrosis factor-α with cycloheximide-induced apoptosis is mediated by mitogen-activated protein kinase pathways

Content Provider	Springer Nature Link
Author	Luo, Peng Zhao, Yongbo Li, Dong Chen, Tao Li, Sanzhong Chao, Xiaodong Liu, Wenbo Zhang, Lei Qu, Yan Jiang, Xiaofan Lu, Gang Poon, Waisang Fei, Zhou
Copyright Year	2012
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 factor-α (TNF-α)/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 TNF-α/CHX-induced apoptotic cell death, whereas inhibition of Homer 1a induction enhanced the pro-apoptotic effect of TNF-α/CHX treatment. Moreover, brain-derived neurotrophic factor, as a potential activator of endogenous Homer 1a, inhibited apoptotic cell death after TNF-α/CHX treatment through induction of Homer 1a. Since three major mitogen-activated 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. Cross-talk 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 death.
Starting Page	975
Ending Page	988
Page Count	14
File Format	PDF
ISSN	13608185
Journal	Apoptosis
Volume Number	17
Issue Number	9
e-ISSN	1573675X
Language	English
Publisher	Springer US
Publisher Date	2012-06-04
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Homer protein Postsynaptic density Mitogen-activated protein kinase Apoptosis Brain-derived neurotrophic factor Virology Biochemistry Oncology Cancer Research Cell Biology
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology

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Protective effect of Homer 1a on tumor necrosis factor-α with cycloheximide-induced apoptosis is mediated by mitogen-activated protein kinase pathways