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: Tatsuya Shimizu, Hideaki Imai, Koji Seki, Shinichiro Tomizawa, Mitsunobu Nakamura, Fumiaki Honda, Nobutaka Kawahara, Nobuhito Saito
• Journal: Journal 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
• PMID: 15647740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Extracellular Matrix Proteins
• Glycoproteins
• Lgals3bp protein, rat
• Nerve Tissue Proteins
• RNA, Messenger
• Cyclophilins
• Cyclophilin C

Topics

• Animals
• Blotting, Northern
• Brain Ischemia (pathology)
• Carrier Proteins (genetics, metabolism)
• Cyclophilin C
• Cyclophilins (genetics, metabolism)
• Extracellular Matrix Proteins
• 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)