MISC

2008年

Chrysotile asbestos causes AEC apoptosis via the caspase activation in vitro and in vivo

INHALATION TOXICOLOGY
  • Takashi Kido
  • ,
  • Yasuo Morimoto
  • ,
  • Etsuko Asonuma
  • ,
  • Kazuhiro Yatera
  • ,
  • Akira Ogami
  • ,
  • Takako Oyabu
  • ,
  • Isamu Tanaka
  • ,
  • Masamitsu Kido

20
3
開始ページ
339
終了ページ
347
記述言語
英語
掲載種別
DOI
10.1080/08958370701866362
出版者・発行元
TAYLOR & FRANCIS INC

To determine whether alveolar epithelial cell (AEC) apoptosis via caspase activation is involved in asbestos-induced lung injury, we examined apoptosis, caspase-3 and-9 activation using chrysotile asbestos exposure models in vitro and in vivo.Apoptotic cells were assessed in A549 cells with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method after 48 hours exposure of chrysotile asbestos (5 to 100 ug/cm2). Asbestos exposure induced a dose-dependent increase of apoptotic cells, and both pretreatment with Z-LEHD-FMK (caspase-3 inhibitor) or Z-DEMK-FMK (caspase-9 inhibitor) significantly suppressed asbestos-induced apoptosis. Expression of cleaved caspase-3 and-9 increased significantly from 18 to at least 48 hours after asbestos exposure. In vivo study, either 1 or 2 mg of chrysotile asbestos were administered into rat lungs intratracheally, and the lungs were obtained 3 days, 1 and 2 weeks, 1, 3 and 6 months after the administration. Asbestos exposure increased the number of apoptotic cells and the activation of cleaved caspase-3 and-9 most at 3 days in a dose dependent manner, and continued to increase them until at least 6 months after asbestos exposure. Apoptotic cells and cleaved caspase-3 and-9 positive cells were mainly observed in AECs. These findings suggest that AEC apoptosis via caspase-3 and-9 activation is involved in asbestos-induced lung injury.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1080/08958370701866362
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000254821900009&DestApp=WOS_CPL

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