title: PDZ1 inhibitor peptide protects neurons against ischemia via inhibiting GluK2-PSD-95-module-mediated Fas signaling pathway.
abstract: Respecting the selective inhibition of peptides on protein-protein interactions, they might become potent methods in ischemic stroke therapy. In this study, we investigated the effect of PDZ1 inhibitor peptide on ischemic neuron apoptosis and the relative mechanism. Results showed that PDZ1 inhibitor peptide, which significantly disrupted GluK2-PSD-95 interaction, efficiently protected neuron from ischemia/reperfusion-induced apoptosis. Further, PDZ1 inhibited FasL expression, DISC assembly and activation of Caspase 8, Bid, Caspase 9 and Caspase 3 after global brain ischemia. Based on our previous report that GluK2-PSD-95 pathway increased FasL expression after global brain ischemia, the neuron protection effect of PDZ1 inhibitor peptide was considered to be achieved by disrupting GluK2-PSD-95 interaction and subsequently inhibiting FasL expression and Fas apoptosis pathway.
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China. Electronic address: yinxiaohui2013@163.com.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yin
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Yan
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China.
authors.forename: Guo
authors.initials: G
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Molecular Biology, Sochoow University, 199 Ren׳ai Road, Suzhou 215002, Jiangsu, PR China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China. Electronic address: xyhou@xzmc.edu.cn.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Hou
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation and the Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR China.
authors.forename: GuangYi
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D051528:Guanylate Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D054731:PDZ Domains; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction; D000097806:GluK2 Kainate Receptor
chemical_list: D020169:Caspases; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor
keywords: Cerebral ischemia; Fas; FasL; GluK2; PSD-95; Peptide