Inhibition of chemokine-like factor 1 protects against focal cerebral ischemia through the promotion of energy metabolism and anti-apoptotic effect.

Abstract

Chemokine-like factor 1 (CKLF1) is a novel C-C chemokine, and plays important roles in immune response and brain development. In previous study, we have found that the expression of CKLF1 increased after focal cerebral ischemia and inhibition of CKLF1 using antagonist C19 peptide protected against cerebral ischemia. However, few studies have focused on the role of CKLF1 on neuronal apoptosis. The objective of present study is to investigate the role of CKLF1 on neuronal apoptosis by applying anti-CKLF1 antibodies in rat focal cerebral ischemia and reperfusion model. Antibodies against CKLF1 was applied to the right cerebral ventricle immediately after transient middle cerebral artery occlusion (MCAO), and infarct volume, neurological score, glucose metabolism and apoptosis-related protein were measured. Treatment with anti-CKLF1 antibody decreased infarct volume and neurological score, and inhibited neuronal apoptosis in a dose-dependent manner at 24h after reperfusion. Anti-CKLF1 antibody also reduced the level of phosphorylation of Akt (P-Akt), and led to decrease of pro-apoptotic protein Bcl-2 associated X protein (Bax) and increase of anti-apoptotic protein B cell lymphoma-2 protein (Bcl-2) and the ratio of Bcl-2/Bax, and inhibited caspase-3 at last. In addition, positron emission tomography (PET) indicated that anti-CKLF1 antibody increased glucose metabolism in ischemic hemisphere. These results suggest that CKLF1 is associated with neuronal apoptosis after cerebral ischemia and reperfusion. Neutralization of CKLF1 with antibodies shows neuroprotective effects against cerebral ischemia, which may be involved in inhibition of Akt pathway, regulation of apoptosis-related protein expression, and improvement glucose metabolism in ischemic hemisphere. Therefore, CKLF1 may be a novel target for the treatment of stroke.

• Authors: Ling Lei Kong, Zhi Yuan Wang, Jin-Feng Hu, Yu-He Yuan, Ning Han, Hua Li, Nai Hong Chen
• Journal: Neurochemistry international (Neurochem Int) Vol. 76 Pg. 91-8 (Oct 2014) ISSN: 1872-9754 [Electronic] England
• PMID: 25042180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Chemokines
• Cklf protein, rat
• MARVEL Domain-Containing Proteins

Topics

• Animals
• Apoptosis
• Brain Ischemia (metabolism, prevention & control)
• Chemokines (antagonists & inhibitors)
• Energy Metabolism
• MARVEL Domain-Containing Proteins (antagonists & inhibitors)
• Male
• Positron-Emission Tomography
• Rats
• Rats, Sprague-Dawley