HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Activation of the Omega-3 Fatty Acid Receptor GPR120 Protects against Focal Cerebral Ischemic Injury by Preventing Inflammation and Apoptosis in Mice.

Abstract
G protein-coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis, but its role in cerebral ischemic injury remains unclear. Using an in vivo model of middle cerebral artery occlusion (MCAO) and an in vitro model of oxygen-glucose deprivation (OGD), we investigated the potential role and molecular mechanisms of GPR120 in focal cerebral ischemic injury. Increased GPR120 expression was observed in microglia and neurons following MCAO-induced ischemia in wild type C57BL/6 mice. Treatment with docosahexaenoic acid (DHA) inhibited OGD-induced inflammatory response in primary microglia and murine microglial BV2 cells, whereas silencing of GPR120 strongly exacerbated the inflammation induced by OGD and abolished the anti-inflammatory effects of DHA. Mechanistically, DHA inhibited OGD-induced inflammation through GPR120 interacting with β-arrestin2. In addition to its anti-inflammatory function, GPR120 also played a role in apoptosis as its knockdown impaired the antiapoptotic effect of DHA in OGD-induced rat pheochromocytoma (PC12) cells. Finally, using MCAO mouse model, we demonstrated that GPR120 activation protected against focal cerebral ischemic injury by preventing inflammation and apoptosis. Our study indicated that pharmacological targeting of GPR120 may provide a novel approach for the treatment of patients with ischemic stroke.
AuthorsZhiping Ren, Lin Chen, Yimeng Wang, Xinbing Wei, Shenglan Zeng, Yi Zheng, Chengjiang Gao, Huiqing Liu
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 202 Issue 3 Pg. 747-759 (02 01 2019) ISSN: 1550-6606 [Electronic] United States
PMID30598514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 by The American Association of Immunologists, Inc.
Chemical References
  • FFAR4 protein, mouse
  • Receptors, G-Protein-Coupled
  • Docosahexaenoic Acids
Topics
  • Animals
  • Apoptosis
  • Brain Ischemia (prevention & control)
  • Disease Models, Animal
  • Docosahexaenoic Acids (pharmacology)
  • Gene Silencing
  • Inflammation (prevention & control)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia (drug effects)
  • PC12 Cells
  • Rats
  • Receptors, G-Protein-Coupled (genetics, metabolism)
  • Stroke (prevention & control)
  • Transcriptional Activation

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: