Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially independent from action of caspases and exhibits necrosis-like features

被引:24
作者
Groebner, Sabine
Autenrieth, Stella E.
Soldanova, Irena
Gunst, Dani S. J.
Schaller, Martin
Bohn, Erwin
Mueller, Steffen
Leverkus, Martin
Wesselborg, Sebastian
Autenrieth, Ingo B.
Borgmann, Stefan
机构
[1] Univ Tubingen, Inst Med Microbiol & Hyg, D-72076 Tubingen, Germany
[2] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany
[3] Univ Tubingen, Dept Internal Med 1, D-72076 Tubingen, Germany
关键词
Yersinia; YopP; apoptosis; necrosis-like; caspase-independent; cell death;
D O I
10.1007/s10495-006-0189-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica that is injected into the cytosol of host cells where it targets MAP kinase kinases (MKKs) and inhibitor of kappa B kinase (IKK)-beta resulting in inhibition of cytokine production as well as induction of apoptosis in murine macrophages and dendritic cells (DC). Here we show that DC death was only partially prevented by the broad spectrum caspase inhibitor zVAD-fmk, indicating simultaneous caspase-dependent and caspase-independent mechanisms of cell death induction by YopP. Microscopic analyses and measurement of cell size demonstrated necrosis-like morphology of caspase-independent cell death. Application of zVAD-fmk prevented cleavage of procaspases and Bid, decrease of the inner transmembrane mitochondrial potential Delta psi(m) and mitochondrial release of cytochrome c. From these data we conclude that YopP-induced activation of the mitochondrial death pathway is mediated upstream via caspases. In conclusion, our results suggest that YopP simultaneously induces caspase-dependent apoptotic and caspase-independent necrosis-like death in DC. However, it has to be resolved if necrosis-like DC death occurs independently from apoptotic events or as an apoptotic epiphenomenon.
引用
收藏
页码:1959 / 1968
页数:10
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