2001年6月
Cytochrome c-mediated caspase-9 activation triggers apoptosis in Streptococcus pyogenes-infected epithelial cells
CELLULAR MICROBIOLOGY
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- ,
- ,
- 巻
- 3
- 号
- 6
- 開始ページ
- 395
- 終了ページ
- 405
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1046/j.1462-5822.2001.00122.x
- 出版者・発行元
- BLACKWELL SCIENCE LTD
Epithelial cells are the initial sites of host invasion by group A Streptococcus pyogenes (GAS), and their infection of epithelial cells has been suggested to induce apoptosis. However, the mechanism responsible for bacteria-host interaction and the induction of apoptosis has not been clearly understood. We demonstrate here that human pharyngeal epithelial HEp-2 cells became apoptotic with DNA fragmentation by invasion of GAS strains JRS4 (M6(+), F1(+)) and JRS145 (M6(-), F1(+) mutant of JRS4), whereas apoptotic cellular changes were not observed in SAM1 (M6(+), F1(-) mutant) or SAM2 (M6(-), F1(-) mutant) infected HEp-2 cells. Confocal microscopy revealed that Bax translocation to mitochondria and cytochrome c release occurred after 4 h of infection. Western blot analyses showed that the amounts of Bcl-2 and Bcl-x(L) were decreased in the mitochondria of infected cells. In addition, we demonstrated that the release of nuclear histone from infected cells was prevented by the addition of caspase-9 inhibitor (Ac-LEHD-CHO). We conclude that the internalization of GAS in epithelial cells is necessary and sufficient for the induction of apoptosis, which is initiated by mitochondrial dysfunction, and the mechanism of GAS-induced apoptosis is clearly different from that induced by other intracellular invasive bacteria, e.g. Shigella and Salmonella species.
- リンク情報
- ID情報
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- DOI : 10.1046/j.1462-5822.2001.00122.x
- ISSN : 1462-5814
- Web of Science ID : WOS:000169156100004