Astrocytic P2Y1 receptor is involved in the regulation of cytokine/chemokine transcription and cerebral damage in a rat model of cerebral ischemia

Kazuya Kuboyama, Hideki Harada, Hidetoshi Tozaki-Saitoh, Makoto Tsuda, Kazuo Ushijima, Kazuhide Inoue

研究成果: Contribution to journalArticle査読

62 被引用数 (Scopus)

抄録

After brain ischemia, significant amounts of adenosine 5′- triphosphate are released or leaked from damaged cells, thus activating purinergic receptors in the central nervous system. A number of P2X/P2Y receptors have been implicated in ischemic conditions, but to date the P2Y 1 receptor (P2Y1 R) has not been implicated in cerebral ischemia. In this study, we found that the astrocytic P2Y1 R, via phosphorylated-RelA (p-RelA), has a negative effect during cerebral ischemia/reperfusion. Intracerebroventricular administration of the P2Y 1 R agonist, MRS 2365, led to an increase in cerebral infarct volume 72 hours after transient middle cerebral artery occlusion (tMCAO). Administration of the P2Y1 R antagonist, MRS 2179, significantly decreased infarct volume and led to recovered motor coordination. The effects of MRS 2179 occurred within 24 hours of tMCAO, and also markedly reduced the expression of p-RelA and interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1/chemokine (C-C motif) ligand 2 (CCL2), and interferon-inducible protein-10/chemokine (C-X-C motif) ligand 10 (CXCL10) mRNA. P2Y1 R and p-RelA were colocalized in glial fibrillary acidic protein-positive astrocytes, and an increase in infarct volume after MRS 2365 treatment was inhibited by the nuclear factor (NF)-B inhibitor ammonium pyrrolidine dithiocarbamate. These results provide evidence that the P2Y 1 R expressed in cortical astrocytes may help regulate the cytokine/chemokine response after tMCAO/reperfusion through a p-RelA-mediated NF-B pathway.

本文言語英語
ページ(範囲)1930-1941
ページ数12
ジャーナルJournal of Cerebral Blood Flow and Metabolism
31
9
DOI
出版ステータス出版済み - 9 2011

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

フィンガープリント 「Astrocytic P2Y<sub>1</sub> receptor is involved in the regulation of cytokine/chemokine transcription and cerebral damage in a rat model of cerebral ischemia」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル