Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Gαi/Gαq-CK2 signaling in ischemic stroke.

Abstract

Cerebral ischemia/reperfusion (I/R) injury-induced neuronal apoptosis contributes to the death and disability in patients with ischemic stroke. However, underlying mechanisms remain elusive and it lacks effective treatment. Here we reported that the expression of casein kinase 2 (CK2) was significantly reduced in brains of middle cerebral artery occlusion/reperfusion (MACO/R) model rats and oxygen-glucose deprivation/reperfusion (OGD/R) model neurons, which was associated with the activation of eIF2-ATF4-CHOP signaling pathway, leading to neuronal apoptosis. Moreover, we found that apelin-13 significantly upregulated CK2 expression and inhibited eIF2-ATF4-CHOP activation, attenuating cerebral I/R injury-induced infarct and neuronal apoptosis in MACO/R model rats and OGD/R model neurons. Furthermore, we demonstrated that the rescue effect of apelin-13 on I/R injury-induced neuronal apoptosis was mediated by Gαi/Gαq-CK2-dependent inhibition of eIF2-ATF4-CHOP activation. These data indicated cerebral I/R injury reduced CK2 expression and activated eIF2-ATF4-CHOP signaling contributing to neuronal apoptosis, and apelin-13 can activate Gαi/Gαq-CK2 signaling attenuating eIF2-ATF4-CHOP-mediated neuronal apoptosis. It provides a novel insight that not only apelin-13 but also CK2 agonists may have therapeutic potential for protecting neurons from I/R injury-induced apoptosis, facilitating post-stroke recovery.

• Authors: Fei Wu, Jian Qiu, Yang Fan, Qiuling Zhang, Baohua Cheng, Yili Wu, Bo Bai
• Journal: Experimental neurology (Exp Neurol) Vol. 302 Pg. 136-144 (04 2018) ISSN: 1090-2430 [Electronic] United States
• PMID: 29337146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Ephrin-B2
• GTP-Binding Protein alpha Subunits
• Intercellular Signaling Peptides and Proteins
• apelin-13 peptide
• L-Lactate Dehydrogenase
• Glucose

Topics

• Animals
• Apoptosis (drug effects)
• Cell Hypoxia (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology)
• Disease Models, Animal
• Endoplasmic Reticulum Stress (drug effects)
• Ephrin-B2 (metabolism)
• GTP-Binding Protein alpha Subunits (metabolism)
• Gene Expression Regulation (drug effects, genetics)
• Glucose (deficiency)
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Injections, Intraventricular
• Intercellular Signaling Peptides and Proteins (therapeutic use)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Neurons (drug effects)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)