title: Apelin-13 protects against apoptosis by activating AMP-activated protein kinase pathway in ischemia stroke.
abstract: Apelin has been proved to be protective against apoptosis induced by ischemic reperfusion. However, mechanisms whereby apelin produces neuroprotection remain to be elucidated. AMP-activated protein kinase (AMPK) is a master energy sensor that monitors levels of key energy metabolites. It is activated via AMPKαThr172 phosphorylation during cerebral ischemia and appears to be neuroprotective. In this study, we investigated the effect of apelin on AMPKα and tested whether apelin protecting against apoptosis was associated with AMPK signals. Focal transient cerebral ischemia/reperfusion (I/R) model in male ICR mice was induced by 60 min of ischemia followed by reperfusion. Apelin-13 was injected intracerebroventricularly 15 min before reperfusion. AMPK inhibitor, compound C, was injected to mice intraperitoneally at the onset of ischemia. In experiment 1, the effect of apelin-13 on AMPKα was measured. In experiment 2, the relevance of AMPKα and apelin-13' effect on apoptosis was measured. Data showed that apelin-13 significantly increased AMPKα phosphorylation level after cerebral I/R. Apelin-13, with the co-administration of saline, reduced apoptosis cells, down-regulated Bax and cleaved-caspase3 and up-regulated Bcl2. However, with the co-administration of compound C, apelin-13 was inefficient in affecting apoptosis and Bax, Bcl2 and cleaved-caspase3. The study provided the evidence that apelin-13 up-regulated AMPKα phosphorylation level in cerebral ischemia insults and AMPK signals participated in the mechanism of apelin-mediated neuroprotection.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@aliyun.com.
authors.forename: Xiang-Jian
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Li-Tao
authors.initials: LT
authors.lastname: Li
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Cui
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Jiang-Yong
authors.initials: JY
authors.lastname: Miao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004789:Enzyme Activation; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C495199:apelin-13 peptide; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Apoptosis; Stroke