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Tumor necrosis factor receptor‐associated factor 6 participates in early brain injury after subarachnoid hemorrhage in rats through inhibiting autophagy and promoting oxidative stress
Author(s) -
Dou Yang,
Shen Haitao,
Feng Dongxia,
Li Haiying,
Tian Xiaodi,
Zhang Jian,
Wang Zhong,
Chen Gang
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14075
Subject(s) - oxidative stress , subarachnoid hemorrhage , medicine , tumor necrosis factor alpha , autophagy , receptor , blood–brain barrier , traumatic brain injury , ubiquitin ligase , intracellular , anesthesia , microbiology and biotechnology , biology , central nervous system , ubiquitin , apoptosis , gene , biochemistry , psychiatry
Tumor necrosis factor receptor‐associated factor 6 ( TRAF 6) is a member of the TRAF family and an important multifunctional intracellular adaptin of the tumor necrosis factor superfamily and toll/ IL ‐1 receptor ( TIR ) superfamily. TRAF 6 has been studied in several central nervous system diseases, including ischemic stroke, traumatic brain injury, and neurodegenerative diseases, but its role in subarachnoid hemorrhage ( SAH ) has not been fully illustrated. This study was designed to explore changes of expression level and potential roles and mechanisms of TRAF 6 in early brain injury ( EBI ) after SAH using a Sprague–Dawley rat model of SAH induced in 0.3 mL non‐heparinized autologous arterial blood injected into the pre‐chiasmatic cistern. First, compared with the sham group, we found that the expression levels of TRAF 6 increased gradually and peaked at 24 h after SAH . Second, the results showed that application of TRAF 6 over‐expression plasmid and genetic silencing si RNA could increase or decrease expression of TRAF 6, respectively, and severely exacerbate or relieve EBI after SAH , including neuronal death, brain edema, and blood–brain barrier injury. Meanwhile, the levels of autophagy and oxidative stress were reduced and increased separately. Finally, GFP ‐ TRAF 6‐C70A, which is a TRAF 6 mutant that lacks E3 ubiquitin ligase activity, was used to explore the mechanism of TRAF 6 in SAH , and the results showed that EBI and oxidative stress were reduced, but the levels of autophagy were increased under this condition. Collectively, these results indicated that TRAF 6 affected the degree of EBI after SAH by inhibiting autophagy and promoting oxidative stress.