title: Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction.
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.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
authors: Lang
authors: L
authors: Wang
authors: Yanyun
authors: Y
authors: Lu
authors: Hongjing
authors: H
authors: Guan
authors: Dingsheng
authors: D
authors: Jiang
authors: Yu
authors: Y
authors: Guan
authors: Xin
authors: X
authors: Zhang
authors: Hiroyasu
authors: H
authors: Nakano
authors: Yan
authors: Y
authors: Zhou
authors: Yan
authors: Y
authors: Zhang
authors: Li
authors: L
authors: Yang
authors: Hongliang
authors: H
authors: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048015:TNF Receptor-Associated Factor 5 / Q000378:metabolism*
chemical_list: D048015:TNF Receptor-Associated Factor 5
keywords: Akt; TRAF5; apoptosis; blood-brain barrier; inflammation; stroke