脳グリア細胞のアポトーシスとその制御

• 田熊 一敞

  神戸学院大学薬学部

書誌事項

タイトル別名

• Delayed Apoptosis and Its Regulation in Astrocytes
• ノウ グリア サイボウ ノ アポトーシス ト ソノ セイギョ

抄録

Astrocytes, the most abundant glial cell type in the brain, are considered to have physiological and pathological roles in neuronal activities. We found that reperfusion of cultured astrocytes after Ca²⁺ depletion causes Ca²⁺ overload followed by delayed cell death and the Na⁺-Ca²⁺ exchanger in the reverse mode is responsible for this Ca²⁺-mediated cell injury (Ca²⁺ paradox injury). The Ca²⁺ paradox injury of cultured astrocytes is considered to be an in vitro model of ischemia/reperfusion injury, since a similar paradoxical change in extracellular Ca²⁺ concentration is reported in ischemic brain tissue. This review summarizes the mechanisms underlying the Ca²⁺-mediated injury of astrocytes and the protective effects of drugs against Ca²⁺ reperfusion injury. This study shows that Ca²⁺ reperfusion injury of astrocytes is accompanied by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species, calcineurin, caspase-3, and NF-κB are involved in Ca²⁺ reperfusion-induced delayed apoptosis of astrocytes. Several drugs including CV-2619, T-588 and ibudilast protect astrocytes against the delayed apoptosis. CV-2619 prevents astrocytes from the delayed apoptosis by production of nerve growth factor, resulting in an activation of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3 (PI3) kinase signal pathways. The protective effect of T-588 is mainly mediated by an activation of MAP/ERK signal cascade. Moreover, ibudilast prevents the Ca²⁺ reperfusion-induced delayed apoptosis of astrocytes via cyclic GMP signaling pathway. Further studies in this system will contribute to the development of new drugs that attenuate ischemia/reperfusion injury via modulation of astrocytes.

収録刊行物

• 薬学雑誌

  薬学雑誌 121 (9), 663-669, 2001-09-01

  公益社団法人 日本薬学会

キーワード

• reperfusion injury
• apoptosis
• MAP kinase
• cGMP
• astrocyte

詳細情報

• CRID: 1390001206126931712
• NII論文ID: 110003661159
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.121.663
• COI: 1:CAS:528:DC%2BD3MXms1eitrc%3D
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 5891590
• PubMed: 11558150
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5891590
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/121/9/121_9_663/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2002079762
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
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