Pathophysiological Significance of Canonical Transient Receptor Potential (TRPC) Subfamily in Astrocyte Activation

• Shirakawa Hisashi

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

Bibliographic Information

Other Title

• アストロサイト異常活性化における TRPC subfamily の生理学的重要性
• アストロサイト イジョウ カッセイカ ニ オケル TRPC subfamily ノ セイリガクテキ ジュウヨウセイ

Abstract

  Astrocytes, the most abundant cells in the central nervous system (CNS), play diverse roles in the regulation of neuronal activity, vascular function and gliotransmitter release. In neurodegenerative diseases, pathologically activated astrocytes show astrogliosis, which is clinically characterized by an abnormal cell morphology and excessive astrocyte proliferation. Thrombin, a crucial factor for brain injury after intracerebral hemorrhage, activates astrocytic Ca²⁺ signaling through a specific subtype of the thrombin receptor, termed the proteinase-activated receptor (PAR). In this study, we demonstrate a novel pathophysiological role for transient receptor potential canonical 3 (TRPC3) Ca²⁺-permeable nonselective cation channels in thrombin-activated astrocytes. In 1321N1 human astrocytoma cells and cultured rat cortical astrocytes, thrombin induced heterogeneous Ca²⁺ responses with asynchronous repetitive peaks. These oscillations were found to be the result of repetitive Ca²⁺ release from intracellular stores followed by replenishment of the stores with Ca²⁺ from the extracellular region. The oscillations occurred without a direct [Ca²⁺]_i increase and were inhibited by the selective TRPC3 inhibitor pyrazole-3. Pharmacological manipulation with BAPTA-AM, cyclopiazonic acid, 2-aminoethoxydiphenyl borate and pyrazole-3 indicated that Ca²⁺ mobilization through TRPC3 was involved in thrombin-induced changes in the morphology of astrocytes. Moreover, thrombin-induced upregulation of S100B, a marker of reactive astrocytes, at 20 h and increased astrocytic proliferation at 72 h were inhibited by Ca²⁺ signaling blockers and knockdown of TRPC3 with specific siRNA. Taken together, these results suggest that TRPC3 may constitute a new therapeutic target for brain injury after intracerebral hemorrhage.<br>

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 132 (5), 587-593, 2012-05-01

  The Pharmaceutical Society of Japan

Keywords

• transient receptor potential canonical subfamily
• astrocyte
• Ca²⁺ mobilization
• thrombin
• S100B
• intracerebral hemorrhage

Details

• CRID: 1390001206126656384
• NII Article ID: 130001888674
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.132.587
• COI: 1:STN:280:DC%2BC38jgslKgug%3D%3D
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 023754071
• PubMed: 22687694
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023754071
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/132/5/132_5_587/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012224133
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed