title: Cyclophilin C-associated protein and cyclophilin C mRNA are upregulated in penumbral neurons and microglia after focal cerebral ischemia.
abstract: Immunophilin ligands, such as cyclosporin A and FK506, have neuroprotective effects in experimental stroke models, although the precise mechanism is unclear. Cyclophilin C-associated protein (CyCAP) is a natural cellular ligand for the immunophilin, cyclophilin C, and has a protective effect against endotoxins by downmodulating the proinflammatory response. Expressions of CyCAP and cyclophilin C mRNA in a rat middle cerebral artery (MCA) occlusion ischemia model were investigated by Northern blotting and in situ hybridization. Both CyCAP and cyclophilin C mRNAs were ubiquitously distributed in the neurons of the normal brain. Expression increased in neurons of the periinfarct zone up to 7 days after MCA occlusion. The neuronal distribution was confirmed by counterimmunostaining of NeuN. Both mRNAs were predominantly expressed in microglia of the ischemic core at 7 days, confirmed by immunostaining with the microglial marker, ED1. The quantification of CyCAP and cyclophilin C mRNAs at 7 days by Northern blot analysis showed the 8.5-fold increase (P<0.005, n=6) and 6.8-fold increase (P<0.005, n=6), respectively, in ischemic core compared with control. The coincidence of CyCAP and cyclophilin C expression in neurons and microglia suggests distinct roles in each cellular population. In particular, the early increase in penumbral neurons might be related to protection in periinfarct neurons.
authors.affiliation: Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Imai
authors.forename: Koji
authors.initials: K
authors.lastname: Seki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tomizawa
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Honda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kawahara
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Saito
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002545:Brain Ischemia / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D000072622:Cyclophilin C; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C492608:Lgals3bp protein, rat; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D021983:Cyclophilins; D000072622:Cyclophilin C