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

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.

• Authors: Yi Yang, Xiangjian Zhang, Haiying Cui, Cong Zhang, Chunhua Zhu, Litao Li
• Journal: Neuroscience letters (Neurosci Lett) Vol. 568 Pg. 44-9 (May 07 2014) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24686182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

• Animals
• Apoptosis (drug effects)
• Brain (drug effects, pathology, physiopathology)
• Brain Edema (pathology, prevention & control)
• Brain Infarction (pathology, prevention & control)
• Brain Ischemia (pathology, physiopathology, prevention & control)
• Caspase 3 (metabolism)
• Chromones (pharmacology)
• Enzyme Activation
• Flavonoids (pharmacology)
• Gene Expression Regulation
• Intercellular Signaling Peptides and Proteins (pharmacology, therapeutic use)
• Male
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Morpholines (pharmacology)
• Neuroprotective Agents (pharmacology, 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