Oleoylethanolamide attenuates apoptosis by inhibiting the TLR4/NF-κB and ERK1/2 signaling pathways in mice with acute ischemic stroke.

Abstract

This study was carried out to investigate the exact mechanisms behind the neuroprotective effects of oleoylethanolamide (OEA) after acute cerebral ischemic injury. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. OEA (40 mg/kg, ip) was administered with a single injection upon reperfusion. The number of apoptotic cells was detected by TUNEL staining. The expression of Bax, Bcl-2, and TLR4, as well as the activities of NF-κB, Akt, and ERK1/2 were analyzed by western blot. Our data showed that OEA treatment alleviated cell apoptosis in a mouse model of ischemic stroke, accompanied by suppression of Bax, as well as upregulation of antiapoptotic protein Bcl-2 level. The changes of Bax and Bcl-2 could not be observed in PPARα knockout mice models with OEA administration. Importantly, OEA inhibited MCAO-induced TLR4 expression, NF-κB activation, IκBα degradation, and ERK1/2 phosphorylation. Our findings demonstrated that the neuroprotective effects of OEA on cerebral ischemia may be attributed to its antiapoptotic property achieved, at least in part, through the PPARα signaling and inhibition of both TLR4/NF-κB and ERK1/2 signaling pathways. These results provide new evidence indicating the neuroprotective effect of OEA on ischemic stroke.

• Authors: Hao Zhou, Wu-Shuang Yang, Ying Li, Tong Ren, Lu Peng, Han Guo, Jin-Feng Liu, Yu Zhou, Yun Zhao, Li-Chao Yang, Xin Jin
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 390 Issue 1 Pg. 77-84 (Jan 2017) ISSN: 1432-1912 [Electronic] Germany
• PMID: 27738712 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• Endocannabinoids
• NF-kappa B
• Neuroprotective Agents
• Oleic Acids
• PPAR alpha
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• oleoylethanolamide
• Mapk1 protein, mouse
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Brain (drug effects, enzymology, pathology)
• Cytoprotection
• Disease Models, Animal
• Endocannabinoids (pharmacology)
• Enzyme Activation
• Infarction, Middle Cerebral Artery (drug therapy, enzymology, pathology)
• Male
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology)
• Oleic Acids (pharmacology)
• PPAR alpha (agonists, metabolism)
• Phosphorylation
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)