Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons
Joint Authors
Liu, Shan
Wang, Xing
He, Sudan
Yu, Xiaoliang
Li, Jun
Xu, Lei
Zhu, Yongjin
Li, Yun
Ge, Lin
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-07-01
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Tumor necrosis factor-α (TNF-α) is a critical proinflammatory cytokine regulating neuroinflammation.
Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear.
Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α.
RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons.
Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells.
HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis.
The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway.
TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines.
Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.
American Psychological Association (APA)
Liu, Shan& Wang, Xing& Li, Yun& Xu, Lei& Yu, Xiaoliang& Ge, Lin…[et al.]. 2014. Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons. BioMed Research International،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-460723
Modern Language Association (MLA)
Liu, Shan…[et al.]. Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons. BioMed Research International No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-460723
American Medical Association (AMA)
Liu, Shan& Wang, Xing& Li, Yun& Xu, Lei& Yu, Xiaoliang& Ge, Lin…[et al.]. Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-460723
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-460723