PMID- 25093162
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2014
DP  - 2014
TI  - Necroptosis mediates TNF-induced toxicity of hippocampal neurons.
PG  - 290182
LID - 10.1155/2014/290182 [doi]
LID - 290182
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a critical proinflammatory cytokine regulating 
      neuroinflammation. Elevated levels of TNF-alpha have been associated with various 
      neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. 
      However, the signaling events that lead to TNF-alpha-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-alpha. RIP3 deficiency attenuates 
      TNF-alpha-initiated loss of hippocampal neurons. Furthermore, we characterized the 
      molecular mechanism of TNF-alpha-induced neurotoxicity in HT-22 hippocampal neuronal 
      cells. HT-22 cells are sensitive to TNF-alpha 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-alpha-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-alpha-induced toxicity of hippocampal neurons, but 
      also demonstrate that TNF-alpha promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of 
      hippocampal neurons largely bypassing ROS accumulation and calcium influx.
FAU - Liu, Shan
AU  - Liu S
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Wang, Xing
AU  - Wang X
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Li, Yun
AU  - Li Y
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Xu, Lei
AU  - Xu L
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Yu, Xiaoliang
AU  - Yu X
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Ge, Lin
AU  - Ge L
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Li, Jun
AU  - Li J
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
FAU - Zhu, Yongjin
AU  - Zhu Y
AD  - Department of Physiology and Neurobiology, School of Biology & Basic Medical 
      Science, Soochow University, Suzhou 215123, China.
FAU - He, Sudan
AU  - He S
AD  - Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated 
      Hospital, Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou, 
      Jiangsu 215123, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140701
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ripk3 protein, mouse)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Hippocampus/metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Necrosis/metabolism/*pathology
MH  - Neurons/metabolism/*pathology
MH  - Phosphorylation
MH  - Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC4100394
EDAT- 2014/08/06 06:00
MHDA- 2015/03/31 06:00
PMCR- 2014/07/01
CRDT- 2014/08/06 06:00
PHST- 2014/03/26 00:00 [received]
PHST- 2014/05/30 00:00 [accepted]
PHST- 2014/08/06 06:00 [entrez]
PHST- 2014/08/06 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - 10.1155/2014/290182 [doi]
PST - ppublish
SO  - Biomed Res Int. 2014;2014:290182. doi: 10.1155/2014/290182. Epub 2014 Jul 1.