Cyclophilin C-associated protein and cyclophilin C mRNA are upregulated in penumbral neurons and microglia after focal cerebral ischemia.

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.
AuthorsTatsuya Shimizu, Hideaki Imai, Koji Seki, Shinichiro Tomizawa, Mitsunobu Nakamura, Fumiaki Honda, Nobutaka Kawahara, Nobuhito Saito
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 25 Issue 3 Pg. 325-37 (Mar 2005) ISSN: 0271-678X [Print] United States
PMID15647740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carrier Proteins
  • Cyclophilin C-associated protein, rat
  • Glycoproteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Cyclophilins
  • cyclophilin C
  • Animals
  • Blotting, Northern
  • Brain Ischemia (pathology)
  • Carrier Proteins (genetics, metabolism)
  • Cyclophilins (genetics, metabolism)
  • Glycoproteins (metabolism)
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Microglia (metabolism, ultrastructure)
  • Nerve Tissue Proteins (genetics, metabolism)
  • Neurons (metabolism, ultrastructure)
  • RNA, Messenger (genetics, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation (genetics)

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