Pro-inflammatory GPR75 and anti-apoptotic phospholipase signaling pathways contribute to the ameliorating effect of soluble epoxide hydrolase inhibition on chronic experimental autoimmune encephalomyelitis in mice

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dc.authoridBAHCELI, OMER/0000-0002-5307-5976
dc.contributor.authorHorat, Mehmet Furkan
dc.contributor.authorSenol, Sefika Pinar
dc.contributor.authorBahceli, Omer
dc.contributor.authorTemiz-Resitoglu, Meryem
dc.contributor.authorSahan-Firat, Seyhan
dc.contributor.authorSevim, Serhan
dc.contributor.authorTunctan, Bahar
dc.date.accessioned2025-03-17T12:25:32Z
dc.date.available2025-03-17T12:25:32Z
dc.date.issued2023
dc.departmentTarsus Üniversitesi
dc.description.abstractSoluble epoxide hydrolase (sEH) inhibition has currently emerged as a therapeutic target in the treatment of various neuroinflammatory neurodegenerative diseases, including multiple sclerosis. Previously, we reported that treatment of mice with an sEH-selective inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy) phenyl]urea; TPPU), ameliorated chronic experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein 35-55 peptide immunization followed by injection of pertussis toxin to mice via regulating pro-inflammatory and anti-inflammatory pathways in the central nervous system. This study tested the hypothesis that the pro-inflammatory G protein-coupled receptor (GPR) 75 and anti-apoptotic phospholipase C (PLC) signaling pathways also contribute to the ameliorating effect of TPPU on chronic EAE. Brains and spinal cords of phosphate-buffered saline-, dimethyl sulfoxide-, or TPPU (3 mg/kg)-treated mice were used for the measurement of sEH, GPR75, G alpha q/11, activator protein (AP)-1, PLC beta 4, phosphoinositide lymphoma (Bcl)-2, semaphorin (SEMA) 3A, and myelin proteolipid protein (PLP) expression and/or activity by using the immunoblotting method. Expression of sEH, GPR75, G alpha q/11, c-jun, phosphorylated c-Jun, and SEMA3A was lower, while PLC beta 4, phosphorylated PI3K p85 alpha, phosphorylated Akt1, phosphorylated MEK1/2, phosphorylated ERK1/2, phosphorylated CREB1, Bcl-2, and myelin PLP expression was higher in the tissues of TPPU (3 mg/kg)-treated mice as compared with the EAE and vehicle control groups. Inhibition of sEH by TPPU ameliorates chronic EAE through suppressing pro-inflammatory GPR75/G alpha q/11/AP-1 pathway and reducing expression of the remyelination inhibitor, SEMA3A, as well as increasing anti-apoptotic PLC/PI3K/ Akt1/MEK1/2/ERK1/2/CREB1/Bcl-2 pathway activity and myelin PLP expression.
dc.description.sponsorshipResearch Fund of Mersin University in Turkey; Scientific and Technological Research Council of Turkey [2018-1-TP3-2814, 221S092]
dc.description.sponsorshipFunding information This study was supported by the Research Fund of Mersin University in Turkey and the Scientific and Technological Research Council of Turkey with project numbers 2018-1-TP3-2814 and 221S092, respectively.
dc.identifier.doi10.14715/cmb/2023.69.10.2
dc.identifier.endpage16
dc.identifier.issn0145-5680
dc.identifier.issn1165-158X
dc.identifier.issue10
dc.identifier.pmid37953590
dc.identifier.scopus2-s2.0-85176800138
dc.identifier.scopusqualityQ4
dc.identifier.startpage9
dc.identifier.urihttps://doi.org/10.14715/cmb/2023.69.10.2
dc.identifier.urihttps://hdl.handle.net/20.500.13099/1717
dc.identifier.volume69
dc.identifier.wosWOS:001104303300007
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherC M B Assoc
dc.relation.ispartofCellular and Molecular Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250316
dc.subjectExperimental autoimmune ence-phalomyelitis
dc.subjectinflammation
dc.subjectsoluble epoxide hydrolase
dc.subjectapoptosis
dc.subjectTPPU
dc.titlePro-inflammatory GPR75 and anti-apoptotic phospholipase signaling pathways contribute to the ameliorating effect of soluble epoxide hydrolase inhibition on chronic experimental autoimmune encephalomyelitis in mice
dc.typeArticle

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