TY  - JOUR
PY  - 2018//
TI  - RIP3 deficiency protects against traumatic brain injury (TBI) through suppressing oxidative stress, inflammation and apoptosis: Dependent on AMPK pathway
JO  - Biochemical and biophysical research communications
A1  - Liu, Zai-Ming
A1  - Chen, Qian-Xue
A1  - Chen, Zhi-Biao
A1  - Tian, Dao-Feng
A1  - Li, Ming-Chang
A1  - Wang, Jun-Min
A1  - Wang, Long
A1  - Liu, Bao-Hui
A1  - Zhang, Shen-Qi
A1  - Li, Fei
A1  - Ye, Hui
A1  - Zhou, Long
SP  - 112
EP  - 119
VL  - 499
IS  - 2
N2  - Traumatic brain injury (TBI) is a leading cause of disability and mortality in young adults worldwide. The pathophysiology is not fully understood. Programmed necrosis (necroptosis) is a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Receptor-interacting protein 3 (RIP3) plays an important role in programmed necrosis. However, the effect of RIP3-related pathway in TBI is little to be known. We attempted to explore the significance of RIP3 in regulating TBI in vivo. Significantly, TBI induced over-expression of RIP3 in the hippocampus of mice, as well as RIP1 and phosphorylated mixed lineage kinase domain-like protein (MLKL). Mice after TBI exhibited cognitive dysfunction and activation of glia cells, which were significantly attenuated by RIP3-knockout (KO). Moreover, inflammation and oxidative stress in hippocampus were markedly induced by TBI in wild type (WT) mice. Of note, the reduction of pro-inflammatory cytokines and oxidants was observed in RIP3-deficient mice, which was linked to the blockage of NLR pyrin domain containing 3 (NLRP3)/apoptosis-associated speck-like protein containing a CARD (ASC)/Caspase-1 and kelch-like ECH-associated protein 1 (Keap 1) pathways. Further, TBI induced hippocampus apoptosis, evidenced by the increase of cleaved Caspase-8/-3 and poly (ADP)-ribose polymerase (PARP) in WT mice, whereas being decreased by RIP3-knockout. In addition, RIP3 knockout led to phosphorylation of AMP-activated protein kinase α (AMPKα) in hippocampus of mice after TBI. And of note, the in vitro findings indicated that RIP3-ablation attenuated oxidative stress, inflammation and apoptosis in astrocytes, which was dependent on AMPKα activation. Together, suppressing RIP3 might be served as a therapeutic target against brain injury through inhibiting inflammation, oxidative stress and apoptosis.<br><br>Copyright © 2018. Published by Elsevier Inc.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-291X
UR  - http://dx.doi.org/10.1016/j.bbrc.2018.02.150
ID  - ref1
ER  -