机构：[a]Department of Neurology, The Affiliated Children Hospital of Soochow University, Suzhou, Jiangsu, China[b]Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China[c]The Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
Apelin is an endogenous ligand of G protein-coupled receptor-apelin and angiotensin-1-like receptor (APJ). The biological effects of apelin-APJ system are reported in multiple systems including cardiovascular, endocrinal, and gastrointestinal system. Previous studies had shown that apelin-13 is a potential protective agent on cardiac ischemia; however, the role of apelin in the central nervous system remained unknown. In this study, we investigated therapeutic effects of apelin-36, a long form of apelin, in ischemic brain injury models. We found that apelin-36 reduced cerebral infarct volume in the middle cerebral artery occlusion (MCAO) model and the neonatal hypoxic/ischemic (H/I) injury model. Apelin-36 improved neurological deficits in the MCAO model and promoted long-term functional recovery after H/I brain injury. We further explored the protective mechanisms of apelin-36 on H/I brain injury. We clearly demonstrated that apelin-36 significantly reduced the levels of cleaved caspase-3 and Bax, two well-established apoptotic markers after H/I injury, indicating the anti-apoptotic activity of apelin-36 in ischemic injury. Since apelin-36 increased the level of phosphorylated Akt after H/I injury, we treated neonates with a specific PI3K inhibitor LY294002. We found that LY294002 decreased the phosphorylated Akt level and attenuated protective effects of apelin-36 on apoptosis. These suggested that the PI3K/Akt pathway was at least in part involved in the anti-apoptotic mechanisms of apelin-36. Our findings demonstrated that apelin-36 was a promising therapeutic agent on the treatment of ischemic brain injury. (C) 2013 Elsevier Ltd. All rights reserved.
基金：
This work was supported by the Ph.D. Program Foundation of
the Ministry of Education of China (20113201120016), the Priority
Academic Program Development of Jiangsu Higher Education Institutions
of China (to XX), and Suzhou Key Laboratory Project on
Brain Development and Treatment of Brain Injury in Children
(SZS201108).
第一作者机构：[a]Department of Neurology, The Affiliated Children Hospital of Soochow University, Suzhou, Jiangsu, China[b]Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China[*2]The Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
推荐引用方式(GB/T 7714)：
Qin Gu,Lijing Zhai,Xing Feng,et al.Apelin-36, a potent peptide, protects against ischemic brain injury by activating the PI3K/Akt pathway[J].NEUROCHEMISTRY INTERNATIONAL.2013,63(6):535-40.doi:10.1016/j.neuint.2013.09.017.
APA：
Qin Gu,Lijing Zhai,Xing Feng,Jing Chen,Zhigang Miao...&Chun-Feng Liu.(2013).Apelin-36, a potent peptide, protects against ischemic brain injury by activating the PI3K/Akt pathway.NEUROCHEMISTRY INTERNATIONAL,63,(6)
MLA：
Qin Gu,et al."Apelin-36, a potent peptide, protects against ischemic brain injury by activating the PI3K/Akt pathway".NEUROCHEMISTRY INTERNATIONAL 63..6(2013):535-40
