Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/Akt and ERK1/2 signaling pathways

Yi Yang; Xiangjian Zhang; Haiying Cui; Cong Zhang; Chunhua Zhu; Litao Li

doi:10.1016/j.neulet.2014.03.037

Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/Akt and ERK1/2 signaling pathways

Neurosci Lett. 2014 May 7:568:44-9. doi: 10.1016/j.neulet.2014.03.037. Epub 2014 Mar 29.

Authors

Yi Yang¹, Xiangjian Zhang², Haiying Cui¹, Cong Zhang¹, Chunhua Zhu¹, Litao Li³

Affiliations

¹ 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.
² 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: [email protected].
³ Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050000, PR China.

PMID: 24686182
DOI: 10.1016/j.neulet.2014.03.037

Abstract

Apelin has been proved to protect the heart against ischemia/reperfusion (I/R) injury via the activation of phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways. Whether this protective effect applies to brain I/R injury needed to be explored. We therefore investigated the potential neuroprotective role of Apelin-13 and the underlying mechanisms. Focal transient cerebral I/R model in male ICR mice was induced by 60min of ischemia followed by reperfusion. Apelin-13 intracerebroventricular injection was performed 15 min before reperfusion. Neurological function, infarct volume, brain edema and apoptosis were measured at 24h after stroke. To further test the mechanism of Apelin-13, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 were injected into the lateral cerebral ventricle 15min before ischemia. Compared with the Vehicle group, Apelin-13 significantly ameliorated neurological deficit, infarct volume, brain edema and reduced TUNEL-positive cells. Bax, caspase-3 and cleaved caspase-3 were down-regulated and Bcl-2 up-regulated. While, the effect of Apelin-13 on Bax, Bcl-2, caspase-3 and cleaved caspase-3 was attenuated by LY294002 and PD98059. Apelin protected the brain against I/R insult injury, and this effect may be through activation of PI3K/Akt and ERK1/2 signaling pathways.

Keywords: Apelin-13; Cerebral ischemia/reperfusion; ERK1/2; PI3K/Akt.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Brain / drug effects
Brain / pathology
Brain / physiopathology
Brain Edema / pathology
Brain Edema / prevention & control
Brain Infarction / pathology
Brain Infarction / prevention & control
Brain Ischemia / pathology
Brain Ischemia / physiopathology
Brain Ischemia / prevention & control*
Caspase 3 / metabolism
Chromones / pharmacology
Enzyme Activation
Flavonoids / pharmacology
Gene Expression Regulation
Intercellular Signaling Peptides and Proteins / pharmacology
Intercellular Signaling Peptides and Proteins / therapeutic use*
Male
Mice, Inbred ICR
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / metabolism*
Morpholines / pharmacology
Neuroprotective Agents / pharmacology
Neuroprotective Agents / therapeutic use*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Reperfusion Injury / prevention & control*
Signal Transduction

Substances

Chromones
Flavonoids
Intercellular Signaling Peptides and Proteins
Morpholines
Neuroprotective Agents
Phosphoinositide-3 Kinase Inhibitors
Proto-Oncogene Proteins c-bcl-2
apelin-13 peptide
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Caspase 3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one