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Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction.

Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction.

Authors :
Wang, Lang
Lu, Yanyun
Guan, Hongjing
Jiang, Dingsheng
Guan, Yu
Zhang, Xin
Nakano, Hiroyasu
Zhou, Yan
Zhang, Yan
Yang, Li
Li, Hongliang
Source :
Journal of Neurochemistry. Aug2013, Vol. 126 Issue 3, p400-414. 15p. 2 Color Photographs, 1 Chart, 7 Graphs.
Publication Year :
2013

Abstract

Tumor necrosis factor receptor-associated factor 5 ( TRAF5) is an adaptor protein of the tumor necrosis factor ( TNF) receptor superfamily and the interleukin-1 receptor/Toll-like receptor superfamily and plays important roles in regulating multiple signaling pathways. This study was conducted to investigate the role of TRAF5 in the context of brain ischemia/reperfusion (I/R) injury. Transient occlusion of the middle cerebral artery was performed on TRAF5 knockout mice ( KO), neuron-specific TRAF5 transgene ( TG), and the appropriate controls. Compared with the WT mice, the TRAF5 KO mice showed lower infarct volumes and better outcomes in the neurological tests. A low neuronal apoptosis level, an attenuated blood-brain barrier ( BBB) disruption and an inhibited inflammatory response were exhibited in TRAF5 KO mice. TRAF5 TG mice exhibited an opposite phenotype. Moreover, the Akt/FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF5 KO mice. These results provide the first demonstration that TRAF5 is a critical mediator of I/R injury in an experimental stroke model. The Akt /FoxO1 signaling pathway probably plays an important role in the biological function of TRAF5 in this model. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00223042
Volume :
126
Issue :
3
Database :
Academic Search Index
Journal :
Journal of Neurochemistry
Publication Type :
Academic Journal
Accession number :
89149706
Full Text :
https://doi.org/10.1111/jnc.12207